2013 Toronto Winter Clinic, Endodontic Pain by Drs. Cherkas & Dorfman
125
New Approaches in Management of Endodontic Pain-- Making Sense of Evidence, Technology and Pharmacogenetics Faculty of Dentistry, University of Toronto, Canada Pavel S. Cherkas DMD, PhD, MMedSc, MSc, BSc Ruslan Dorfman PhD, MBA, MSc, BSc
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2013 Toronto Academy of Dentistry, 76th Annual Winter Clinic New Approaches in Management of Endodontic Pain by Dr. Pavel S. Cherkas, Endodontist-Neuroscientist and Dr. Ruslan Dorfman, Molecular Geneticist
Transcript of 2013 Toronto Winter Clinic, Endodontic Pain by Drs. Cherkas & Dorfman
New Approaches in Management of
Endodontic Pain-- Making Sense of
Evidence Technology and
Pharmacogenetics
Faculty of Dentistry University of Toronto Canada
Pavel S Cherkas DMD PhD MMedSc MSc BSc
Ruslan Dorfman PhD MBA MSc BSc
Agenda for todayrsquos course
bull Anatomical structures in pain
signaling
bull Pain modalities
bull Acute pain as risk factor of chronic
pain
bull Levels of evidence
bull Pain as diagnostic tool
bull Evidence based pain management
bull Anthropologic risk factors of pain
bull Pre-op pain ndash local anesthetics
bull Opioids ndash when and what is
appropriate
bull NSAIDs for analgesia
bull Antiepileptic drugs for pain control
bull Break - 10 min
bull Anesthesia ndash maximum results
bull Technologies for root canal
treatment
bull Antibiotics in endodontic treatment
bull Statin-macrolide drug interactions
bull Differences in NSAID response
bull Use of steroids
bull Outlook into future
bull Conclusions
Do we know more today
Can we treat better
Peripheral innervation patterns cannot explain
pain referral
Acute vs Chronic Dental Pain
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
Acute Pain Transient usually sharp pain that serves a protective function warns the organism of actual or impending tissue injury
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Agenda for todayrsquos course
bull Anatomical structures in pain
signaling
bull Pain modalities
bull Acute pain as risk factor of chronic
pain
bull Levels of evidence
bull Pain as diagnostic tool
bull Evidence based pain management
bull Anthropologic risk factors of pain
bull Pre-op pain ndash local anesthetics
bull Opioids ndash when and what is
appropriate
bull NSAIDs for analgesia
bull Antiepileptic drugs for pain control
bull Break - 10 min
bull Anesthesia ndash maximum results
bull Technologies for root canal
treatment
bull Antibiotics in endodontic treatment
bull Statin-macrolide drug interactions
bull Differences in NSAID response
bull Use of steroids
bull Outlook into future
bull Conclusions
Do we know more today
Can we treat better
Peripheral innervation patterns cannot explain
pain referral
Acute vs Chronic Dental Pain
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
Acute Pain Transient usually sharp pain that serves a protective function warns the organism of actual or impending tissue injury
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Do we know more today
Can we treat better
Peripheral innervation patterns cannot explain
pain referral
Acute vs Chronic Dental Pain
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
Acute Pain Transient usually sharp pain that serves a protective function warns the organism of actual or impending tissue injury
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Peripheral innervation patterns cannot explain
pain referral
Acute vs Chronic Dental Pain
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
Acute Pain Transient usually sharp pain that serves a protective function warns the organism of actual or impending tissue injury
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Acute vs Chronic Dental Pain
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP)
Acute Pain Transient usually sharp pain that serves a protective function warns the organism of actual or impending tissue injury
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Chronic Pain
Chronic Pain Persistent often dull or aching
pain that continues long after an injury has
apparently healed (gt 3 months duration)
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial region eg 10-15 prevalence of toothache or TMD
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Uncontrolled acute pain increases the risk of
chronic pain
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8 9 10 11 12
Series2
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12
P(T)
P(T)
P(T) = GB Int[I(t)dt] where P(T) is the probability of developing chronic condition by time T
Cherkas 2013
Uncontrolled acute pain increases the risk of
chronic pain
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pain control what works and what does not
bull Pre-op anesthesia ndash and NSAIDs
bull Local anesthesia
bull Post-op anesthesia ndash and NSAIDs vs opioids
bull Antibiotics
bull Steroids
Each treatment is associated with benefits and risks ndash need to balance both
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
AAE Definitions of Pulpitis
Reversible pulpitis ndash A clinical diagnosis based upon subjective and objective findings indicating that the inflammation should resolve and the pulp return to normal
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Irreversible pulpitis ndash A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed pulp is incapable of healing Additional descriptions Symptomatic ndash Lingering thermal pain spontaneous pain referred pain Asymptomatic ndash No clinical symptoms but inflammation produced by caries caries excavation trauma etc
AAE Definitions of Pulpitis
Take home message
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ldquoHot toothrdquo
bull pulp diagnosed with irreversible pulpitis with spontaneous moderate-to-severe pain
bull patient who is sitting in the waiting room sipping on a large glass of ice water to help control the pain
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ldquoHot toothrdquo
bull Chronic inflammation takes on an acute exacerbation
bull Influx of neutrophils
bull Release of inflammatory mediators
bull Release of proinflammatory neuropeptides
bull Peripheral and central sensitization of nociceptors
bull Increased neuronal excitability
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers underwater divers
Pain or injury affecting teeth due to changes in pressure gradients
Boylersquos Law ldquoat a given temperature the volume of a gas is inversely proportional to the ambient pressurerdquo
Robichaud amp McNally 2005
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pain as a Diagnostic Tool
Lack of knowledge concerning the type characterization and variety of fractures may lead to misunderstanding with incorrect diagnosis and inappropriate treatment bull Craze Lines
bull Split Tooth
bull Fractured Cusp
bull Vertical Root Fracture bull Cracked Tooth
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Craze Lines Fractured and Split Teeth
Craze lines affect only the enamel while fractured cusps cracked teeth and split teeth begin on the occlusal surface and extend apically affecting enamel dentin and possibly the pulp
Craze lines Fractured cusp Cracked tooth
Take home message
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Case 1
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Radiographic Examination
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Radiographic Examination
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Apical surgery and bone grafting
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Apical surgery and bone grafting
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Apical surgery and bone grafting
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Case 2 (Apical surgery)
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Case 3 (Apical surgery)
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q The teeth with irreversible pulpitis that are the most difficult to anesthetize are
1 the mandibular molars followed by mandibular premolars maxillary molars and maxillary premolars
2 the maxillary molars and maxillary premolars mandibular molars followed by mandibular premolars
3 the mandibular molars followed by maxillary molars mandibular premolars and maxillary premolars
4 maxillary anterior teeth
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
aAge Gender Body weight
bRace
c Hair color
da+b
ea+b+c
Q What anthropologic factors contribute to
response to opioid anesthesia
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A B C
D E F
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q Who has higher pain sensitivity and
stronger response to opioid anesthesia
A
Red hair = 2 mutations in MC1R gene melanocortin 1 receptor
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Red-haired women are more sensitive to morphine
Mogil J S et al J Med Genet 200542583-587
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans
2 variants = red hair
Women are more sensitive
black vs yellow (ee) MC1R mutant mice
10 mgkg morphine
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Anesthetic efficacy of the inferior alveolar nerve block in red-haired women
bull Red hair and the MC1R gene were significantly linked to higher levels of dental anxiety
bull but were unrelated to success rates of the IAN block in women with healthy pulps
Droll et al 2012
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pre-Operative Pain Control
bull Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
bull Epinephrine is contraindicated in patients who have used cocaine within the last 24-48 hours
Sofuoglu et al 2001 Take home message
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local anesthetic with vasoconstrictors in untreated hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the vascular effect of thyroid hormone
Take home message
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamine-producing tumors
The use of vasoconstrictors puts these patients at high risk for lethal cardiac or cerebrovascular complications and should be strictly avoided
Perusse and Goulet 1992
Take home message
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
bull Clinical studies in endodontics in patients with irreversible pulpitis have found success with the inferior alveolar nerve block occurred
between 15 and 57 of the time
Al Reader et al 2011 Take home message
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Combination of preoperative ibuprofenacetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
bull a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success
Simpson et al J Endod 2011
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Is a dose of 36 mL better than 18 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis
bull For patients presenting with irreversible pulpitis success was not significantly different between a 36-mL volume and a 18-mL volume of 2 lidocaine with 1100000 epinephrine
Fowler and Reader J Endod 2013
Take home message
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Why do we get anesthetic failures
1 Anatomical variations
ndash central core theory
ndash Spread of the solution within the pterygomandibular space
Hargraves 2002
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Lip numbness
bull Lip numbness can be obtained in 100 of the time
bull Successful anesthesia in 15 -57 of the time
bull The lack of lip numbness following IANB indicates the injection was missed- no anesthesia
bull Once lip numbness is achieved lack of pulpal anesthesia is not due to an inaccurate inferior alveolar nerve block
Al Reader et al 2011
Take home message
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Tachyphylaxis
2 Tachyphylaxis appears neither to be linked to structural or pharmacological properties of the local anesthetics nor to the technique or mode of their administration
The mechanisms underlying tachyphylaxis are open to debate and include changes in pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher amp Peters 1999
Take home message
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Why do we get anesthetic failures
3 Effect of Inflammation on local tissues (pH)
4 Effect of Inflammation on blood flow ndash vasodilation
5 Effect of Inflammation on nociceptors ndash allodynia
6 Effect of Inflammation on central sensitization
7 Psychological factors
7 Genetic factors - variations in drug metabolic genes
Hargreaves 2002
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
WHO Analgesic Ladder
Analgesic Ladder World Health Organization 1986
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Typical situation
Patient comes back within 24 hours after a treatment and complains of severe pain You prescribe Tylenol 3
Next morning the patient is back in your office with acute pain and asks for stronger pain killer
bull What should I prescribe to alleviate the pain
bull Is this real or heshe is a drug seeker
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Next best treatment options
A Tylenol 4
B Percocet
C Oxycontin or Tramadol
D Celecoxib
Q Patient on Tylenol 3 reports only minor pain relief
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
httppharmgkbblogspotca201302fda-to-post-black-box-warning-on-codeinehtml
Non-responders are poor CYP2D6 metabolizers
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Tylenol 3 non-responders
bull Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine thus do not experience pain relief
bull Oxycodone and Tramadol are metabolized by CYP2D6
bull Percocet (acetaminophen and oxycodone) ndash the same
bull These patients do not benefit from Oxycodone
Tramadol Tramacet and Percocet
bull Respond well to morphine and fentanyl and COX-2
inhibitors
Take home message
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
Q Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Next best treatment option is
A Tylenol 4
B Oxycontin or Tramadol
C Morphine
D Celecoxib
R
Q Patient on Tylenol 3 reports short-term pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Most likely the patient is ultrafast CYP2D6 metabolizer
Patient on Tylenol 3 reports only short term pain relief
Stamer amp Stuber Expert Opin Pharmacother (2007)
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Ethnic variability of CYP2D6 alleles
Stamer amp Stuber Expert Opin Pharmacother (2007)
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Acute Post-Endodontic Pain
Reported incidence ndash 16 to 66 within one week
Typically treated with short-term analgesics
Al-Negrish et al 2006 Imura et al 1995 Morse et al 1987 Trope 1991
Walton amp Fouad 1992
Analgesics ineffective in 3 of affected patients
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Persistent Post-Endodontic Pain
Reported incidence ndash 55 (range of 3-12) beyond six months
Estimated 34 is of non-odontogenic origin
Campbell et al 1990 Marbach et al 1982 Polycarpou et al 2005 Keenan 2010
Nixdorf et al 2010 Cherkas ampSessle 2012
In the US ndash 870000 in Canada ndash96000 -new casesyear
In the US ndash 550000 in Canada ndash61000 non-odontogenic pain
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Analgesia
Postoperative analgesia is no different from other areas of medicine in that we all have strong opinions and often the stronger the opinion the weaker is the underlying evidence
HJ McQuay DM University of Oxford
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Adverse side effects are rare and underreported
bull Collecting evidence about harm in postoperative pain receives much less attention than evidence about efficacyhellip
bull Rare (serious) adverse effects are not likely to be detected in small randomised trials
bull Adverse side effects create liability risk for your practice
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Unfiltered information
Filtered information
Levels of evidence
Systematic Reviews
Evidence Synthesis amp Guidelines
Critically Apprised Individual Articles
Randomized Controlled Trials
Case-control Studies amp Case Series and reports
Background information Expert Opinion
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Analgesic
Number
of
patients
in
comparis
on
Percent
with at
least
50
pain
relief
NNT
Dipyrone 1000 113 79 16
Ibuprofen 600800 165 86 17
Ketorolac 20 69 57 18
Ketorolac 60 IM 116 56 18
Diclofenac 100 545 69 18
Piroxicam 40 30 80 19
Celecoxib 400 298 52 21
Paracetamol 1000
+ Codeine 60 197 57 22
Oxycodone IR 5 +
Paracetamol 500 150 60 22
Bromfenac 25 370 51 22
Rofecoxib 50 675 54 23
Oxycodone IR 15 60 73 23
Aspirin 1200 279 61 24
Bromfenac 50 247 53 24
Dipyrone 500 288 73 24
Ibuprofen 400 5456 55 25
The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the proportion of patients with at least 50 pain relief over 4-6 hours compared with placebo in randomised double-blind single-dose studies in patients with moderate to severe pain
httpwwwmedicineoxacukbandolierboothpainpagAcutrevAnalgesicslftabhtml
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
R
What may work for Tylenol 3 non-responders
1 COX2 inhibitors (valdecoxib celecoxib)
2 Higher doses of ibuprofen
3 Anti-epileptic (carbamazepine or pregabalin)
4 Morphine
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al 2013
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0
002
004
006
008
01
012
014
016
018
Pre
Day
1
Day
3
Day
5
Day
7 P
re
60
m
12
0m
18
0m
Day
10
Day
14
Day
21
Day
21
Pre
60
m
12
0m
18
0m
Day
22
Day
28
Day
35
Day
42
Day
49
Pre
60
m
12
0m
18
0m
Day
56
He
ad w
ith
dra
wal
th
resh
old
Time
Naiumlve
Aceta 100mgKg
PG 75mgkg
IONX
Cherkas et al 2013
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Break - 10 min
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Marbach 1978 Harris 1978 Graff-Radford et al 1986 Rees amp Harris 1978 Baad-
Hansen 2008 Zakrzewska 2010 2011
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain rdquopain arising as a direct consequence of any lesion or disease
affecting the somatosensory systemrdquo
Incidence can be as high as 3 to 6
International Association for the Study of Pain 2011
Take home message
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
What do we do for better anesthesia
Alternate injection locations bull Gow-Gates and Vazirani-Akinosi
bull Incisive nerve block at the mental foramen
bull Mandibular infiltration following IANB
Supplemental LA bull Intraligamental
bull Intrapulpal
bull Intraosseus
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Anesthetic efficacy of X-tip intraosseous injection using
2 lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
bull 93 of X-tip injections were successful
Verma et al 2013
Take home message
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Al Reader et al 2011
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Al Reader et al 2011
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection
1 Tooth with symptomatic irreversible pulpitis
2 Tooth with asymptomatic irreversible pulpitis
3 Tooth with reversible pulpitis
4 Asymptomatic tooth with necrotic pulp
5 Symptomatic tooth with necrotic pulp and PA radiolucency
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Painful teeth with necrotic pulp and PA
radiolucencies
bull In this condition intraosseous and intrapulpal injections are painful and may not be effective
bull Intraosseous and intrapulpal injections should not be used in painful teeth with necrotic pulps and radiolucent areas
Al Reader et al 2011
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Flare-up
As specifically defined by Walton (2002) interappointment flare-up has the following 4 criteria
1 Within a few hours to a few days after an endodontic procedure a patient has significant increase in pain or swelling or a combination of the two
2 The problem is of such severity that the patient initiates contact with the dentist
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
bull 3 The dentist determines that the problem is of such significance that the patient must come for an unscheduled visit
bull 4 Active treatment is rendered That may include incision for drainage canal debridement opening the tooth prescribing appropriate medications or doing whatever is necessary to resolve the problem
Flare-up
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Flare-up - Frequency
bull Overall incidence low
bull Best evidence suggest true frequency ranges from 15 to 55
bull Some studies showing frequency high as 16
bull Variation due at least in part to study design (prospective retrospective) how cases defined sample size etc
Walton 2002 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Causes of Post-op Pain
bull Central sensitization
bull Microbial
bull Non-microbial
(mechanical or lsquophysicalrsquo chemical)
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Causes of Post-op Pain
bull Microbial causes are the most common and most important cause of post-operative pain in endodontics
bull Non-microbial causes (mechanical chemical even thermal in rare instances) are typically iatrogenic
Seltzer and Naidorf 1985 Siqueira and Barnett 2004
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ClinicalRisk Factors for Post-op Pain or
Flare-Up
Related to Presenting SignsSymptoms
ndash With pre-op pain increased risk
ndash With pre-op swelling increased risk
bull With pre-op pain increased stress levels may lead to
impaired immune capabilities
Logan et al 2001 Walton 2002
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
ClinicalRisk Factors for Post-op Pain or
Flare-Up
bull Related to Treatment Procedures ndash Single visit versus multi-visit ndash no difference in risk
(Sathorn 2008 Figini 2008)
ndash Incomplete debridement or overinstrumentation increased risk
ndash Obturation ndash decreases the risk
May be due to fact that operators wonrsquot obturate cases with extreme presenting signssymptoms
Walton 2002
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash Operative
Treatment
Choices
ndash Re-instrumentation
ndash Cortical trephination
ndash Incision and drainage
ndash Intracanal medicaments
ndash Occlusal reduction
Siqueira and Barnett 2004
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
I think the adequate working length is shown in ___
A B C
1 A 2 B 3 C 4 B+C 5 None
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
I think the adequate working length is shown in ___
A B C
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
What is the best cell phone for my family
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
EndoVac
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Plazas-Garzon and Cherkas 2013
Negative pressure irrigation
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation
Gondim E Jr et al 2010
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash
Pharmacological Treatment
bull Antibiotics
bull Local Anesthetics
bull Analgesics
ndash Acetaminophen
ndash NSAIDs
ndash Opioid analgesics
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q Post-Operative Pain Control -
Antibiotics
bull Are systemtic antibiotics effective in relieving lsquountreatedrsquo pulpal pain
bull Answer NO
bull Nagle et al 2000 (penicillin had no analgesic effect in cases of irrversible pulpitis)
Fouad 2002
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q Post-Operative Pain Control -
Antibiotics
bull Question Are systemtic antibiotics effective in relieving localized post-op periapical symptoms
bull Answer NO
ndash In patients with pulp necrosis and symptomatic AP addition of systemic penicillin provided no added benefit to the painful condition beyond that of chemomechanical canal instrumentation alone
Fouad 2002 Henry et al 2001
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
What DOESNrsquoT Work for Post-Op Pain
1 Antibiotics Walton and Chiappinelli (JOE rsquo97) Fouad Rivera and Walton (OOOO 96) Henry Reader and Beck (JOE 2001) Effect on incidence of flare ups Pickenpaugh Reader et al (JOE 2001)
2 Narcotics as a first choice medication Systematic reviews (Moore et al 2005-13)
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Indications for Antibiotics Use in
Endodontics
bull AHA Prophylaxis
bull Diffuse swelling (cellulitis)
bull Localized swelling without drainage
bull Rapidly increasing swelling
bull Systemic signs (fever lymphadenopathy
unexplained trismus)
bull Trauma
bull Regeneration
Take home message
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Q You are considering to prescribe a
macrolide antibiotic
Your major concerns are
a) Patients prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Antibiotics Be aware of statins
Link E Parish S Armitage J Bowman L Heath S Matsuda F Gut I Lathrop M and Collins R (2008) The SEARCH Collaborative Group N Engl J Med 359789-799
rs4149056 pVal174Ala
Macrolides can exacerbate the risk of kidney failure especially in elderly and patients with reduced kidney function
18 of statin users experience muscle pain as a result of rhabdomyolysis that may lead to kidney failure
SLCO1B1
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
httpwwwpharmgkborgpathwayPA145011109
Clarithromycin Erythromycin
Azithromycin
Azythromycin has a lower risk of statin
interaction
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Statins and microlides can lead to kidney
failure Statin toxicity from macrolide antibiotic coprescription a population-based cohort study Patel AM Shariff S Bailey DG Juurlink DN Gandhi S Mamdani M Gomes T Fleet J Hwang YJ Garg AX Ann Intern Med 2013 Jun 18158(12)869-76
ldquoCompared with azithromycin coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis or with acute kidney injuryrdquo
bull Patients reporting muscle pain while taking statins are at increased risk of kidney damage while on macrolides
bull thus should temporarily discontinue statins
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
1 Preoperative hyperalgesia
2 Females
3 Apical Periodontitis
4 Necrotic Pulp
Hutter and Hargreaves (2011)
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
1 Pre-op pain is a good predictor or post-op pain 2 On average pain is maximal in first 24-48 hrs ndash no need to give pain meds for more than a few days with proper clean and shape of the canal
Torabinejad et al (JOE 2002)
Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash Local
Anesthetics
bull LA can be used for sole purpose of pain relief or in conjunction with operativesurgical procedures to reduce post-op pain
bull Most useful in cases involving mandibular teeth where bupivacaine (long-acting LA) is administered by mandibular block injection
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
bull bupivacaine 05
ndash available with 1200000 epinephrine
ndash trade name Marcaine (Vivacaine ndash new US only)
wwwkodakdentalcom
Post-Operative Pain Control ndash Local
Anesthetics
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Haas 2002
Post-Operative Pain Control ndash Local
Anesthetics
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Bupivacaine-induced cardio toxicity
Excessive plasma concentrations due to
ndash inadvertent intravascular injection
ndash excessive dose or rate of injection
ndash administration into vascular tissue
ndash delayed drug clearance (CYP3A4)
Agent
Minimum
Toxic Dose
(mgkg)
Procaine 192
Tetracaine 25
Chloroprocain
e 228
Lidocaine 64
Mepivacaine 98
Bupivacaine 16
Etidocaine 34
Minimum Intravenous Toxic Dose of Local Anesthetic
Goldfrank LR et al 1507-17 In Goldfranks
Toxicologic Emergencies 6th ed New York
McGraw-Hill 1998897-903
Myocardial depression and bradycardia and cardiovascular collapse
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
The 3D Strategy for Treating Endodontic Pain
1 Differential Diagnosis of non odontogenic pain P ndash Psychogenic ndash Munchausens I ndash Inflammatory ndash Sinusitis N ndash Neurovascular ndash Cluster headaches S ndash Systemic ndash Myocardial Infarct M ndash Musculoskeletal ndash Myofacial pain (TMD)
Hargreaves 2011
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
The 3D Strategy for Treating Endodontic Pain
2 Definitive Dental Treatment
bull anesthesia (anatomy all current evidence based techniques)
bull EndoVac (negative pressure) Bupivacaine etc 3 Drugs
bull NSAIDs bull Opioids
Hargreaves 2011
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control Analgesics ndash
Algorithm
Hargreaves and Seltzer 2002
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
vs
Inactivated by CYP2C9
CYP2E1 converts acetaminophen into N-acetyl-p-benzoquinoneimine
(NAPQI) bull Celecoxib bull Lornoxicam bull Diclofenac bull Naproxen
bull Ketoprofen bull Piroxicam bull Meloxicam bull Suprofen
Preferred for patients on warfarin or other blood
thinners
Poor CYP2C9 metabolizers experience better pain relief
bull NAPQI is the active metabolite bull increases risk of liver toxicity
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Acetominophen and Ibuprofen
Substantially greater analgesia than either drug alone AND avoids the side effects of opiates
Cooper et al combined Ibuprofen 200 mg + APAP 650 (Compendium) was better than either alone
Derry et al 2011(Br Dent j 2011)
Mehninick (IEJ 2004)
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Cox-2 specific inhibitors
bull Very effective in controlling inflammatory pain
bull Long term exposure leads to increased risk of heart failure
bull Most effective Cox-2 blockers were pulled off the market
bull How to balance benefits and risks
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
httpwwwpharmgkborgpathwayPA165816736
bull Coxibs metabolized by CYP2C9
bull Poor metabolizers have increased exposure to celecoxib bull better pain control bull increased risk of heart attack
and GI bleeding
bull Warfarin is metabolized by CYP2C9
bull Co-administration can increase risk of intracranial bleeding
bull Need to check the INR
Gong Li et al 2012
Coxibs pain relief and risk of CVD and GI bleed
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen and ASA an alternative NSAID should be used or ibuprofen should be taken at least 30 min after or at least 8 h before ASA
AHA 2007
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Before recommending NSAIDs for pain control
Ask the patient whether
a Suffering from ulcers or GI bleeding
b Abusing alcohol or has reduced liver function
c Taking aspirin or antiplatelet medication (Plavix Effient)
d Warfarin or another anticoagulant (Xarelto)
bull Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
bull Seek advise if pain persists over 3 days
Take home message
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash Steroids
bull Glucocorticoids inhibit many cells and factors present in inflammatory response
bull Inhibition of gene transcription for inflammatory factors
bull Inhibition of pro-inflammatory cytokine production
Marshall 2002
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash Steroids
ldquoThe administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment painrdquo
ldquoSystemic steroids are also highly effective in those patients who
present for treatment with moderate severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucencyrdquo
Marshall 2002
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Post-Operative Pain Control ndash Steroids
Is the benefit worth the risk given the side effect profile (ex avascular necrosis of the hip from a single oral steroid dose) and given the efficacy of available analgesics
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Atypical odontalgia
Cherkas and Sessle 2012
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pain Associated with Irreversible Pulpitis
What is the best time for treatment
Acute inflammation Acute inflammation
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Today (2013-14)
Todayrsquos patients are under the impression that only classic methods of pain control apply to endodontics
We now have ldquomolecular approachesrdquo that offer us different methods of pain control
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Today (2013-14)
httpwwwpersonalizedmedicinecoalitionorg
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
DNA tests ndash can predict drug response
and the risk of side effects
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Conclusion
Post-operative pain and flare-up
DefinitionsFrequency (25-40 vs 2-6)
Causes ndash bacterial chemical physical
Clinical Risk Factors
Prevention ndash may not be entirely possible
Temporal summation (central sensitization)
Post-Operative Pain Control (Management)
Operativesurgical ndash reinstrumentation IampD etc
Pharmacological ndash analgesics LA (steroids Ab)
Patients respond differently to treatments
Adverse side effects are preventable
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Future directions
bull More targeted pain treatments (minocycline)
bull Proactive interventions to reduce the risk of
chronic pain
bull Implementation of new endodontic techniques
bull Personalized approach to pain management
bull Reduced incidence of adverse side effects
bull Happier and healthier patients
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
Pavel Cherkas pavelendoartca EndoArtca Ruslan Dorfman ruslangeneyouinca wwwgeneyouinca Phone 647-868-1812
Thank you
Please fill the feedback form after completing your test
