Miorilass in day surgery
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Transcript of Miorilass in day surgery
I Miorilassanti in day surgery-day anesthesia
Claudio Melloni
Servizio di Anestesia e Rianimazione
Ospedale di Faenza(RA)
Caratteristiche del miorilassante ideale in day surgery-day
anesthesia• Fast onset & fast offset
• assenza di blocco residuo– asssenza necessità di antagonizzazione….
• assenza di effetti collaterali;istaminoliberazione,effetti cardiovascolari…
• predicibilità durate
• sicurezza
• indipendenza da organi….(ma Asa dei paz,ambulat...)
Problemi dei miorilassanti in day anesthesia……...
Fast onset
Fast offset
No blocco residuoEvita antagonismo
No metaboliti attivi
Mancanza effetti collaterali
Profilodi
sicurezza
Facile conservabilità e
Valutazione rischio/beneficio
No blocco residuo
No metaboliti attivi
No liberazione di istamina;no effetti emodinamici
Evita antagonismo
Facile conservabilità/utilizzo
Indipendenza da organi sicurezza
Valutazione del blocco residuo
• Valutazione della ripresa neuromuscolare:– prima del risveglio:
• valutazione della forza contrattile in risposta alla stimolazione:MMG,EMG.accelerometria,qualitative e quantitative:TOF,DBS,tetano 50,100 HZ…….;
• TV,RR,forza insp ed esp
– dopo il risveglio,volontarietà:• sollevamento testa> 5 sec
• sollevamento braccio
• stretta di mano
• protrusione lingua
• apertura ampia occhi
Assiomi della ripresa nm.
• TOF > 0.70 sicuro indice della ripresa nm……….. Ali HH, Wilson RS, Savarese JJ, Kitz RJ: The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans. Br J Anaesth 47:570-4, 1975
• Brand JB, Cullen DJ, Wilson NE, Ali HH: Spontaneous recovery from nondepolarizing neuromuscular blockade: Correlation between clinical and evoked responses. Anesth Analg 56:55-8, 1977
Mutazioni occorse
• Esplosione della chirurgia ambulatoriale
• pressione per la diminuzione della spesa sanitaria
• aumento delle persone anziane e debilitate anche in chir amb.
• Disponibilità di nuovi farmaci
Kopman AF, Yee PS, Neuman GG: Relationship of the train-of-four fade ratio to clinical signs and
symptoms of residual paralysis in awake volunteers. ANESTHESIOLOGY 86:765-71, 1997 • 10 healthy, unpremedicated, and unanesthetized volunteers
underwent baseline testing of neuromuscular function, followed by administration of a single 5- g/kg bolus of mivacurium + continuous infusion at 2 g×kg-1×min-1.
• Nm function tested using TOF stimulation and was recorded EMG
Kopman 2;
• When the target TOF ratio of 0.65—0.70 was achieved, the mivacurium infusion was titrated to maintain a stable TOF ratio of 0.70.
• All volunteers then repeated the tests of neuromuscular function, and the mivacurium infusion then was titrated to allow recovery to a TOF ratio of 0.85—0.90.
• Nm function tests repeated, and the mivacurium infusion was discontinued to allow full recovery.
• All volunteers were observed until they believed they were back to “normal.”
Kopman 3:risultati
• The results are as surprising as they are significant: all volunteers reported considerable visual disturbances even when the TOF ratio had recovered to 0.90. Head- and leg-lift usually were present at a TOF ratio of ³0.60, whereas at a TOF ratio of <0.75, all volunteers felt uncomfortable, some reporting persistence of diplopia “for periods in excess of 1 hour after termination of the mivacurium infusion.” From a monitoring standpoint, of all clinical tests of neuromuscular function, the most sensitive (when compared with the TOF ratio) was the ability of the volunteers to resist the removal of a wooden tongue blade from their clenched teeth.
Rivalutazione della pratica clinica
• Età e stato di salute differiscono fra volontari sani e pazienti!
• La prassi clinica e l’utilizzo dei miorilassanti variano fra i diversi centri ambulatoriali
• il monitoraggio degli effetti nm non è praticato in ospedale,figurarsi nei centri ambulatoriali!
• I metodi di monitoraggio usati da Kopman et al si applico ad una ampia gamma di situazioni cliniche.
• Esistono pesanti pressioni economiche per la diminuzione della spesa sanitaria.
Implicazioni del lavoro di Kopman:1
• I paz chirurgici sono in genere più anziani e ammalati dei volontari sani dello studio di Kopman/( ASA 1, entro il 15% del peso ideale,tra 23—33 anni….)
• gli effetti residui dei miorilassanti è probabile possano essere + significativi nella pratica ambulatoriale con pazienti + anziani e debilitati.
• Si potrebbe arguire che i paz.con sedazione residua siano meno attenti a disturbi visivi e
• debolezza dei muscoli facciali;ma è anche vero che dal punto di vista della sicurezza i paz postop siano esposti a rischio maggiore di aumento della morbilità,poichè la debolezza residua nm può essere aggravata da residui dell’anestesia.
Implicazioni del lavoro di Kopman:2
• mivacurium non è rappresentativo dei miorilassanti usati in chir amb;il mercato è dominato dai miorilassanti ad azione intermedia quali vecuronium, atracurium, rocuronium, cisatracurium
• se una paralisi residua permane per un’ora dopo interruzione del mivac,caratterizzato da un RI di pochi min,che succede dopo la somministrazione dei mioril a durata intermedia(RI 20-30 min )?
Day surgery/ anesthesia e LMA
Miorilassanti, Anestetici, analgesici
• stimolazione cardiovascolare
riprese più rapidedimissioni più precoci
dati sul ORG9487(Wierda)
0
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t125% tof20% T190 tof70%
SucciORG9487ORG9487+neo
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confronto fra succi,ORG9487,mivacurium
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succiORG9487Mivac
tempi di ripresa 25-75%
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Lien CA,Belmont MR,Abalos A,Hass D,SavareseJJ.The nature of spontaneous recovery from
mivacurium induced neuromuscular block.AA1999;88:648-53.
• Hypothesis:– in a given patient recovery from an initial or
intubating dose of mivacurium would indicatethe time course of spontaneous recovery afterdiscontinuation of an infusion of mivac.
1:Lien CA,Belmont MR,Abalos A,Hass D,SavareseJJ.The nature of spontaneous recovery from mivacurium
induced neuromuscular block.AA 1999;88:648-53.
• 38 paz
• 27-52 anni
• ASA 1 & 2
• urology
• anest:midaz,fent,prop
• iot senza miorilass
• mant;N2O/O2,prop inf cont,fent
• TOF,meccanomiografia(Grass).
3:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.Thenature of spontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Mivac 0.3 mg/kg in due dosi a distanza di30 sec.
• Al 25% di T1,mivac inf cont allo scopo dimantenere 95% di blocco.
• Ripresa spontanea
4:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.Thenature of spontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Mivac infusion rate:7.1 microgr/kg/min +/-1.7
• durata infusione:30-241 min.
• tempo richiesto per la ripresa spontaneadopo interruzione della infusione di mivacnon correlata alla durata della infusione dimivac.
Tempi di ripresa dopo mivacurium,bolo e infus.cont.;dati daLien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.The nature of spontaneousrecovery from mivacurium induced neuromuscular block.AA 1999;88:648-53.
0
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5-25%dopo bolo5-25% dopo infusT1-T3 dopo bolobolo-T1bolo -25%T125-75% dopo infus5-95% dopo infusfine infus-Tof70%fine infus-Tof 90%
Tempi di ripresa dopo mivacurium,bolo einfus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos
A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacuriuminduced neuromuscular block.AA 1999;88:648-53.
• Tempo di ripresa del I twitch palpabiledopo il bolo correlato al tempo dalla finedella infus alla ripresa del TOF 70%:
• T= 8.8 + 0.3*x :intervallo di confidenza95% 13.5-15.8
Tempi di ripresa dopo mivacurium,bolo einfus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos
A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacuriuminduced neuromuscular block.AA 1999;88:648-53.
• RI 5-25% dopo il bolo relato al temporichiesto dalla fine infusione al tof70%:T=10.3+ 1.1*x (13.5-15.3 min)
• tempo bolo-5%T1 relato al tof 70 e al tof90%: T=-0,5 +1*x (16.2-22.3 min)
Tempi di ripresa dopo mivacurium,bolo einfus.cont:conclusioni;dati da Lien CA,BelmontMR,Abalos A,Hass D,Savarese JJ.The nature ofspontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Per ogni paz,la ripresa nella funzione nm dopocessazione dell’ inf.cont di miva è legata allaripresa iniziale dopo la dose bolo di 0.3 mg/kg.
• Ogni paziente è l’indicatore della propria ripresa.
Kahwaji R,Bevan DR,Bikhazi G,Shanks CA,Fragen RJ,Dyck JB,Angst MS,Matteo R.Dose ranging stuy in younger adults and elderly patients of ORG 9487,a new rapid onset ,short duration muscle relaxant.Anesth.Analg 1997;84:1011-8.
Studio prospettico,randomizzato,assessor blind,multicentrico,descrittivoTPS/fentanyl/N2O e infus cont di propofolmonitoraggio EMG con Datex Relaxographdosaggi di ORG 9487;0.5/1/1.5/2/2.5 mg/kgripresa spontanea
Condizioni di intubazione a 60 sec nei pazienti<65 anni
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pazienti
placebo 0.5 mg/kg 1 mg/kg 1.5 mg/kg 2 mg/kg 2.5 mg/kg
eccellentebuonacattivaimpossibile
Condizione di intubazione nei pazienti > 65 anni
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placebo 0.5mg/kg
1 mg/kg 1.5mg/kg
2 mg/kg 2,5mg/kg
eccellentebuonacattiva
Dati sull’onset e sulla ripresa di ORG 9487
0102030405060708090
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plac
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1.5
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T1 60 secpiccodur 25%dur T4/T1 70%
Conclusioni su ORG 9487
Condizioni di intubazione buone/eccellenti in 90 sec in quasi tutti i pazienti con dosi > o = 1.5 mg/kgdurate cliniche< 20 min a <2 mg/kg nei giovani e 1.5 mg/kg negli anzianibroncospasmo con tachicardia in 2 /148 pazientiriprese dose dipendenti
Selettività di ORG 9487
Vagal/soleus:3(76 per vecu e 8 per rocu)ganglion/soleus; 24
Purdy R,Bevan DR,Donati F,Lichtor,L.Early reversal of rapacuronium with neostigmine.Anesthesiology 1999;91:51-7.
ASA 1-3premed con diaz o midazanest:fent/propofol + inf cont propofol 50-300 g/min +N2Omeccanomiografia,STrapacuronium 1.5 o 2.5 mg/kg:iot a 60 sec.:tre gruppi in studio :
no reversal0.05 mg/kg neostigmina + glicopirrolato 0.01 mg/kg0.07 mg/kg neostigmina+ glicopirrolato 0.01 mg/kgdopo o 2 o 5 min
Riprese del T1 25%
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neo 0 neo 0.05a 2 min
neo 0.07a 2 min
neo0.05 a5 min
neo 0.07a 5 min
rapa 1.5rapa 2.5
Ripresa del T1 75 %dopo rapacuronium
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neo 0.07a 2 min
neo0.05 a5 min
neo 0,07a 5 min
rapa 1.5rapa 2.5
RI del rapacuronium
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TOF 0.7 dopo rapacuronium
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Quoziente di sicurezza:ED95 istaminoliberatrice/ED95 blocco nm.
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atracmivaccisatrac
??
Problemi della succinilcolina � Spasmi muscolari
� rabdomiolisi:crush syndrome,shock ipovolemico,aritmie cardiache,IRA mioglobinurica….
� ipertermia maligna(miopatie,distrofie muscolari,CCD……)
� mialgie:0.2-89%………:femmine,laparoscopie…..
� Iperkaliemia
� spasmo del massetere,rigidità
� crisi miotoniche
� disturbi cardiovascolari
� anafilassi
� impredicibilità di effetti
� aum.IOP
� aum press intragastrica
� aum ICP
Fattori che influenzano le mialgie da succi
• Tipo di pretrattamento:
• miorilassante non depolarizzante• fenitoina• BDZ• clorpromazina• vit E• anlgesico FANs(aspirina,ketorolac….)• analgesico oppioide• grado del blocco pregiunzionale
• intervallo fra non depolarizzante e succi
• velocità di azione del non depolarizzante
• dose della succi
Findlay GP,Spittal MJ. Rocuronium pretreatment reduces suxamehonium induced
myalgia:comparison with vecuronium.BJA 1996;76:526-29.
• 150 patients • elective oral surgery• effectiveness and sequelae of pretreatment with rocuronium for reducing
myalgia after suxamethonium
• Patients allocated randomly to one of three groups: anaesthesia induced with propofol and fentanyl, and group V received vecuronium 1 mg, group R rocuronium 6 mg and group P placebo pretreatment
• Suxamethonium 1.5 mg kg-1 60 s after the pretreatment agent. • All patients:ketorolac 10 mg i.v. and morphine 10 mg i.m. for analgesia.
• incidence of postoperative myalgia compared:
– Intubating conditions were not affected adversely by any pretreatment regimen.
Incidenza di mialgie dopo succi 1.5 mg/kg preceduta da piccola dose di vecu,rocu o
placebo(da Findlay GP,Spittal MJ. Rocuronium pretreatment reduces suxamehonium induced myalgia:comparison with
vecuronium.BJA 1996;76:526-29.)
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day 1 day 4
vecu 1 mgrocu 6 mgplacebo
Nimmo S M, McCann N, Broome IJ, Robb HM.Effectiveness and sequelae of very low dose suxamethonium for nasal intubation.BJA
1995;74:31-34
• day–case oral surgery • requiring nasal intubation• Anaesthesia induced with propofol and alfentanil• 3 groups: no suxamethonium, suxamethonium 0.25
mg kg-1 or 0.5 mg kg-1. • All patients received i.v. fentanyl and diclofenac
100 mg rectally for analgesia.
Nimmo et al.Effectiveness and sequelae of very low dose suxamethonium for nasal
intubation.BJA 1995;74:31-34
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%
day 1 day 5 facilità intub
incidenza di mialgie in chir.orale ambulatoriale
succi 0.25 mg/kgsucci 0.5 mg/kgno succi
Tang J,Joshi G, White PF.Comparison of rocuronium and mivacurium to succinylcholine
during outpatient laparoscopic surgery.Anesth Analg 1996; 82:994–8.
• 100 healthy women undergoing outpatient laparoscopic surgery
• fentanyl-thiopental induction
• tracheal intubation :– succinylcholine 1 mg/kg in Groups I and II – rocuronium 0.6 mg/kg in Group III – mivacurium 0.2 mg/kg in Group IV– If clinically indicated, bolus doses of rocuronium 5–10 mg (Groups I and III) or mivacurium 2–4 mg (Groups II and IV) were
administered during the maintenance period– Anesthesia maintained with desflurane and nitrous oxide 60% in oxygen.– At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 mg/kg, – The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the
wrist.– Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time
(from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 ± 21 s and 62 ± 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 ± 76 s) or mivacurium (210 ± 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was no difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of 45action increases the need for reversal drugs.
Risultati dello studio di Tang et al.
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succi 1mg/kg +
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rocu 0,6mg/kg
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cattiva iot a 90 seceritemamialgie reversal needcosto
Tempi di azione e di ripresa dello studio di Tang et al.
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Conclusioni dello studio di Tang et al.
• Intubating conditions 90 sec dopo miorilass:succi & rocu + rapidi del mivac
• onset time_:succi + breve di rocu + breve di miva• recovery times T1 25% :succi & miva + brevi di rocu• reversal;succi & miva no;rocu sì• eritema : con mivac!• Postoperative myalgia;succi 16% vs 0 dei
nondepolarizz.• PONV =.
Watcha MF, Safavi FZ, McCulloch DA, et al. Effect of antagonism of mivacurium-induced
neuromuscular block on postoperative emesis in children. Anesth Analg 1995; 80:713-7.
• The routine use of cholinesterase inhibitors to antagonize residual neuromuscular block may be associated with increased postoperative emesis.
• Rapid spontaneous recovery from mivacurium may obviate the need for these drugs.• randomized, double-blind, placebo-controlled study • 113 healthy children • incidence of postoperative complications after spontaneous recovery and after the use of neostigmine-
glycopyrrolate or edrophonium-atropine. • anesthetic regimen :halothane, nitrous oxide, fentanyl, 2 micrograms/kg mivacurium in an initial dose
of 0.2 mg/kg, followed by an infusion, adjusted to maintain > or = 1 evoked contraction response to a supramaximum train-of-four stimulus.
• At the end of the procedure, patients received by random assignment one of three drug combinations: 1) neostigmine 70 micrograms/kg + glycopyrrolate 10 micrograms/kg, i.v., 2) edrophonium 1 mg/kg + atropine 10 micrograms/kg, i.v., and 3) saline.
• trachea extubated when evoked responses to peripheral nerve stimulation and clinical signs of adequate neuromuscular recovery were present.
• Postoperative pain was treated with morphine and emesis with metoclopramide.
Watcha MF, Safavi FZ, McCulloch DA, et al. Effect of antagonism of mivacurium-induced
neuromuscular block on postoperative emesis in children. Anesth Analg 1995; 80:713-7.
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PONV antiemeticinecess
Vomitoentro 24
ore
Incidenza di PONV nella PACU
neostigmine 70micrograms/kg +glycopyrrolate 10micrograms/kg, edrophonium 1 mg/kg +atropine 10micrograms/kg.
saline
**
Ding Y,Fredman B, White PF.Use of mivacurium during laparoscopic surgery:effect of reversal
drungs on postoperaive recovery.Anesth Analg 1994; 78:450–4
• outpatient laparoscopic tubal ligation • 60 healthy, nonpregnant women. • midazolam / fentanyl/tps• succ 1 mg/kg (Group I) vs mivacurium 0.2 mg/kg (Groups II
and III)• Anesthesia maintained with isoflurane (0.5%-2% +67% N2O• Muscle relaxation maintained in all three groups with
intermittent bolus doses of mivacurium, 2–4 mg, IV.• In Group III, residual neuromuscular block reversed with
neostigmine 2.5 mg +glycopyrrolate, 0.5 mg,
Effetti collat dello studio di Ding et al.
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nau
sea
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it
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emet
ici
nec
k p
ain
shou
lder
pai
n
succi/miva/no antag
miva/miva/ no antagmiva/miva/antag
*
**
*
Boeke AJ, de Lange JJ, van Druenen B, Langemeijer JJM. Effect of antagonizing residual
neuromuscular block by neostigmine and atropine on postoperative vomiting. Br J Anaesth
1994; 72:654-6.• 80 patients undergoing outpatient surgery
• allocated randomly to two groups: in group A residual neuromuscular block was antagonized with a mixture of neostigmine 1.5 mg and atropine 0.5 mg; in group B spontaneous recovery was allowed.
• patients assessed after operation in hospital and 24 h after discharge.
Boeke AJ, de Lange JJ, van Druenen B, Langemeijer JJM. Effect of antagonizing residual neuromuscular block
by neostigmine and atropine on postoperative vomiting. Br J Anaesth 1994; 72:654-6.
• inguinal hernia repair & stripping of the major saphenous vein of one leg.
• no premed
• atropine 0.5 mg i.v.
• anaesthesia : tps 5–8 mg/kg + fent 2 g/kg
• vecu.0.1 mg kg-1.
• 100% oxygen * 3 min
• iot
• IPPV 66% N2O/ haloth. 0.5%
Incid.di PONV nello studio di Boeke et al.
02468
101214161820
num.paz
PONV RR PONV I PONV II antiemetici
antagnon antag
*
Boeke et al.;risultati e conclusioni.
• We found a significant difference (P < 0.05) in requirements for antiemetic therapy with a smaller need in the group which received neostigmine (in group A four of 40 patients received an antiemetic compared with 12 in group B).
• no significant difference in frequency of nausea or vomiting between the two groups.
• The incidence of postoperative nausea was 14 in group A and 18 in group B and the number of patients with postoperative vomiting was 10 in group A and 15 in group B.
• In conclusion, as there was an increase in the number of patients requiring antiemetics in group B compared with group A (P < 0.05), the results of this study may suggest an antiemetic effect of neostigmine.
Costi Diretti:
acquisto conservazione
indiretti: trattamento ;
lib istaminamialgiebocca seccaPONV…..
prolungamento degenza,:sala op,RR,Pacu...Ospedalizzazione non prevista aumento del discomfort,ansietà,stress…
Kao YJ, Mian T, McDaniel KE, et al. Neuromuscular blockade reversal agents induce postoperative nausea and
vomiting [abstract] Anesthesiology 1992; 77(Suppl):A1120.
05
101520253035
%
PONV
Minilap per PPTL.Tps/succi/iot/fent/isof/N2O.Stomaco svuotato.Atrac 0.15 mg/kg.
no antag
A 0.15 micrG/kg + edroph 1mg/kg
A 0.15 micrg/kg+neo 0.05mg/kg
A 0.15 icrg/kg+pirido 0.25mg/KG
*
Zahl K,Apfelbaum JL.Muscle pain occurs after outpatient laparoscopy despite the substitution of
vecuronim for succinylcholine.Anesthesioloogy 70;408-11,1989.
• 35 paz sane non gravide per lap diagnostica • questionario su dolore (VAS) in 11 regioni corporee;compilato
alla sera dell’op. e poi I,II,III giorno postop.• no premed• fent 2 g/kg,tps 6 m/kg:poi iot dopo succi 1.5 mg/kg( DTC
pretratt.) vs vecu 0.05 mg/kg.• Posiz litotomica• mantenim con N2O + tps/fent as required• ST mantenuto al T1 10% con dosi addiz di vecu o infus di scc.• Vecu antagonizzato con edroph/glicopir.
Zahl K,Apfelbaum JL.Risultati
00,5
11,5
22,5
33,5
44,5
5
dolore
occh
i
man
dib
gola
bra
ccio
coll
o
spal
le
dor
so
add
ome
nat
ich
e
cosc
ia
pol
pac
cio
succivecu
Zahl K,Apfelbaum JL.Risultati
Zahl K,Apfelbaum JL.:conclusioni
• Nessuna differenza nelle frequenze e severità del dolore nelle varie regioni corporee ai vari tempi
Fragen RJ,Shanks CA.Neuromuscular recovery after laparoscopy.Anesth.Analg.63;51-4.1984.
• 60 pz sane
• laparoscopia:30-60 min.
• anest:tps/N2O +fent o isof.
• vecu 0.045 mg/kg vs panc 0.07 mg/kg
• tof:meccanomiografia e EMG
• antag se tof<0.80 alla fine dell’intervento;edroph 0.5-0.6 mg/kg + atropa 7-10 g/kg.eventualmente ripetuti .
Risultati monitoraggio nm.(da Fragen RJ,Shanks CA.Neuromuscular recovery after
laparoscopy.Anesth.Analg.63;51-4.1984.
0102030405060708090
100sec,
min,
%
onse
t
tim
e to
mx
bloc
k
20 m
inT
1%
t4/t
1 fi
neop ri
prsp
ont
anta
gne
cess
II d
ose
anta
g
vecupanc
Risultati ripresa nm.(da Fragen RJ,Shanks
CA.Neuromuscular recovery after laparoscopy.Anesth.Analg.63;51-4.1984.
010
2030
40
5060
70
8090
% paz.
d
epr.
forz
a
dep
rst
rett
a
erro
riT
rieg
er
dip
lop
ia
d
epr.
forz
a
dep
rst
rett
a 30
'
erro
riT
rieg
er
vecupanc
Entro 30 min Entro 60 min
Poler SM,Luchtefeld G,White PF.Comparison of mivacurium and succinylcholine during
outpatient laparoscopy.Anesthesiology 1989,69:A 523.
• 42 paz per laparoscopia
• drop+metoclopr
• EMG
• alf 20 g /kg+tps 3.5 mg/kg;poi
• 3 gruppi– succi 1mg/kg+inf 60 g/kg/min+alf 1 g /kg/min – mivac 0.15 mg/kg+inf 6 g /kg/min+alf 1 g /kg/min – mivac 0.15 mg/kg+inf 6 g /kg/min+ enfl 1%
Risultati dello studio di Poler et al.
• Onset + breve con succi
• iot time + lungo con mivac
• recovery + rapido con succi
• no reversal con succi:75% con miva(infus cessata 5 min prima della fine operaz)
• no diff in mialgie
• flush cutaneo nel 38% dei paz dopo mivac.
Goldberg ME,Larijani GE,Azad SS,Sosis M,Seltzer JL,Ascher J,Weakly JN. Comparison of trcheal intubating conditions and
neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical
outpatients.Anesth.Analg.1989,69.93-9.
• 30 outpatients
• tps/fent/N2O 70%+ fent
• MMG, tof
• gruppi:
– succi 1 mg/kg
– mivac 0.20 mg/kg
– mivac 0.25 mg/kg
– nm block continuato con inf cont di succi o mivac.
Tempi di ripresa da Goldberg et al( con MIR di 40 g/kg/min per succi e 6.6 per mivac)
05
1015202530354045
sec o
min
onse
t(t1
10%
)
dur
5%
RI2
5
Ri 5
0
RI
75
RI
95
anta
g
succimivac 0.20mivac 0,25
%
Indici di ripresa a 2-3 ED95
0
5
10
15
20
25
30
35
RI 5-95% RI25-75%
mivacatracvecu
Da Goldberg et al.
Da Miller et al.Anesthesiology 1984 ;61:444
Whalley D,Maurer WG, Knapik AL,Estafanous FG.Comparison of neuromuscular effects,efficacy and safety of rocuronium and atracurium in ambulatory
anesthesia.Can J Anaesth 1998 / 45 / 954-959.
• studio comparativo randomized, assessor-blinded per gli effetti nm,cardiovascolari di dosi equipotenti di rocu vs atrac
• chir laparoscopica ambulat.• 41 paz:
– 2 x ED90 rocuronium (0.6 mg×kg-1; n = 20) – atracurium (0.5 mg×kg-1; n = 21)
• anest. propofol/alfentanil/ N2O/O2 • MMG,TOF• confronto fra condiz iot,cardiovasc,eventi avversi
Risultati dello studio di Whalley. et al.
0
10
20
30
40
50
60
70
80
90
100
onset iot<90 sec dur 25% RI 25-75 Tof 0.70
rocuatracsec
min
min
min%
RI da Whalley & Hans(Hans P, Brichant JF,
Franzen A, Faleres X, Lamy M. Comparison of neuromuscular block of atracurium and rocuronium in adults. Acta Anaesthesiol Belg 1996;
47:53-8. )
0
2
4
6
8
10
12
14
16
18
RI Whalley RI Hans
rocuatrac
N2ON2O
enfluranoenflurano
Conclusioni da Whalley et al.
• Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.
Chetty MS, Pollard BL, Wilson A, Healy TEJ. Rocuronium bromide in dental day case anaesthesia - a comparison with atracurium and vecuronium. Anaesth
Intensive Care 1996; 24:37-41. • intubating conditions at 60 seconds, onset times and
reversal characteristics of rocuronium with atracurium and vecuronium.
• Middle age,m & f .
• 1.75 X ED90 of each agent used to assess their relative suitability for brief day case dental procedures requiring intubation
• anestesia: propofol, fentanyl, N2O/ isoflurane.
• EMG
Risultati di Chetty et al.
0
10
20
30
40
50
60
70
80
successo iot60"
blocco % a60"
dur25% Ri con neo
rocuatracvecu
% paz
%
min
min
Stevens J,Walker SC, Fontenot JP. The clinical neuromuscular pharmacology of cisatracurium
versus vecuronium during outpatient anestesia.Anesth Analg 1997; 85:1278–83
• 165 ASA I and II patients • elective outpatient procedures (primarily orthopedic, otolaryngologic,
gynecologic, and plastic surgery) • midaz/alfent/propofiot N2O + propofol• 120 patients received cisatracurium 5, 10, or 15 g/kg or normal saline
placebo followed 5 min later by either cisatracurium 100 g/ /kg or vecuronium 100 g/ /kg (always after placebo).
• MMG• When the evoked response spontaneously recovered to 10% of control
height, neostigmine 5, 10, 30, or 50 g/ /kg or placebo was administered, and recovery of neuromuscular function was recorded for the next 15 min.
•
Risultati dello studio di Stevens et al.
• clinical onset of vecuronium without priming (2.8 ± 0.8 min) (mean ± SD) was significantly (P < 0.05) faster than the onset of cisatracurium without priming (4.6 ± 1.4 min).
• Cisatracurium 5, 10, or 15 g/ /kg administered before cisatracurium 100 g/ /kg significantly (P < 0.05) accelerated the time to complete ablation of the evoked response (3.9 ± 0.9, 2.9 ± 0.8, or 3.0 ± 0.9 min, respectively) compared with cisatracurium 100 g/ /kg without priming.
• The dose of neostigmine required to achieve 50% assisted recovery of the train-of-four ratio at 5 min was significantly (P < 0.05) smaller in patients who received vecuronium (29.1 [17.9–55.3] g/ /kg) (mean [95% confidence interval]) compared with those who received cisatracurium (53.7
[31.6–131.5] g /kg).
dati di farmacodinamica da Stevens et al.
0
10
20
30
40
50
60
7080
90
t1 90 sec t1 95%depr
T1 zero T1 10%
cis 100 microgr/kgci5 + cis 100cis 10+ cis 100cis 15 + cis 100vec 100
Tempi per il tof > 0.70 nello studio di Stevens et al.
0
2
4
6
8
10
12
min
neo 50 micrgr/kg neo 30 microgr/kg
cisatracvecu
Conclusioni di Stevens et al.
• Although priming with 10 or 15 g/kg cisatracurium resulted in a 35% reduction in clinical onset compared with cisatracurium 100 g /kg alone, the clinical onset of cisatracurium with priming was not significantly different from the clinical onset of vecuronium 100 g /kg without priming.
• both cisatracurium and vecuronium are readily antagonized to a TOF ratio of 0.7 with neostigmine.
• Patients who received vecuronium, however, recovered to a TOF ratio >0.7 faster than those who received cisatracurium.
• Further, our results suggest that a larger dose of neostigmine is required to rapidly antagonize
cisatracurium than to rapidly antagonize vecuronium.
Conclusioni di Stevens et al
• Given its faster clinical onset and greater sensitivity to antagonism by neostigmine, we conclude that vecuronium may be more suitable than cisatracurium for use in outpatient anesthesia.
Criteri di scelta dei miorilassanti in day surgery-day anesthesia
• Conoscenza dei tempi chir e anest;
• dosi non >1-1.5 ED 95;
• monitoraggio ;
• vietati i miorilassanti a durata lunga:
• evitare antagonismo se possibile
• scelta fra:
– Rapacuronium,rocuronium vecuronium – mivacurium,atracurium,cisatracurium.
Indicazioni di massima per l’uso dei miorilassanti in day surgery-day anesthesia
• Chirurgia < 30 min: Rapacuronium o mivacurium,monodose.
• chirurgia 30-60 min:monodose di rocuronium,vecuronium,atracurium,cisatracurium :
– 2-3 ED di rapacuronium o monodose di mivac + inf cont
• chirurgia 60-90 min:dose iniziale di rocuronium,vecuronium,atracurium,cisatracurium con dose rip possibile opp mivacurium monodose + inf cont.
• chirurgia 90-120 min;tutti i precedenti,sia a dosi rip che mivac inf cont.
• Chirurgia che si prolunga inaspettatamente;dose inziale di qualsiasi + miva inf cont o dosi rip.
Future trends
– fast onset & offset,senza cumulatività……..
– no metaboliti attivi– indipendente da organi– no effetti cardiovascolari– (selettivo per gruppi muscolari…)
Miraculorium