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LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
LABORATORY ANIMALS:Rodent Anesthesia & Analgesia
V-9054
Kathleen A. Murray, DVM, MS
Director, Technical Operations
Charles River Laboratories, Inc.Wilmington, Massachusetts
Cinthia Pekow, DVM
Chief, Veterinary Medical Unit, Research
Veterans Affairs Puget Sound Health Care System
Seattle, Washington
Gary L. Borkowski, DVM, DACLAM
Attending Veterinarian & Associate Director
Pharmacia Corporation
St. Louis, Missouri
The Laboratory Animal Medicine and Science - Series II has been developed by the AutotutorialCommittee of the American College of Laboratory Animal Medicine (ACLAM): C.W. McPherson,
DVM, Chair; J.E. Harkness, DVM; J.F. Harwell, Jr., DVM; J.M. Linn, DVM; A.F. Moreland, DVM,
G.L. Van Hoosier, Jr., DVM; L. Dahm, M.S.
Laboratory Animal Medicine and Science Series II
is produced by the
Health Sciences Center for Educational Resources
University of Washington
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2 LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
University of Washington
Health Sciences Center for Educational Resources
Box 357161, Seattle, WA 98195 -7161 206/685-1157
Copyright 2000
by the University of Washington Health Sciences Center forEducational Resources and the American College of Laboratory
Animal Medicine
All rights reserved.
Printed in the United States of America.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 3
PRIMARY AUDIENCE Veterinarians, investigators, and research technicians.
SECONDARY AUDIENCE Veterinary students, laboratory animal care technicians.
GOAL To provide guidelines for a comprehensive rodent anesthesia
and analgesia program.
OBJECTIVES When you complete this program, you should be able to:
1. Explain the unique challenges in rodent anesthesia.
2. List the criteria used to select an appropriate anesthetic.
3. List characteristics of individual animals that affect anesthetic
choice.
4. Describe the advantages and disadvantages of injectableadministration of anesthesia.
5. Describe the advantages and disadvantages of inhalant
administration of anesthesia.
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4 LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
1. Series Laboratory Animal Medicine and Science Series II
2. Title Rodent Anesthesia & Analgesia
3. Objectives When you complete this program, you should be able to:
1. Explain the unique challenges in rodent anesthesia.
2. List the criteria used to select an appropriate anesthetic.
3. List characteristics of individual animals that affect anesthetic
choice.
4. Describe the advantages and disadvantages of injectable
administration of anesthesia.
5. Describe the advantages and disadvantages of inhalant
administration of anesthesia.
4. Introduction Rodent anesthesia offers unique challenges that are infrequently
encountered in any other veterinary setting. Among the unique
challenges in rodent anesthesia is that often surgery is done on morethan one animal at a time in an "assembly-line" or "herd" fashion. To
accommodate the simultaneous anesthesia of multiple animals, it is
useful to have an anesthetic solution available that can be
administered based on body weight and that is fairly tolerant of 5, 10,
or 20 g weight differences among the patients. This allows parenteral
administration of anesthesia on a milliliter per kilogram basis with
premixed dilutions or combinations of drugs.
5. Unique Factors There are many anesthetic drugs that have been developed for use in
humans or in other animals. Extrapolation of dosages for rodents is
sometimes difficult. On the other hand, some anesthetic agents are
used only in rodents, but there is very little physiologic, toxicologic, or
pathologic information in the literature about their efficacy. In addition,
the various species and strains of rodents may show differing
sensitivity, efficacy, and duration with various anesthetics. Monitoring
physiologic parameters during anesthesia in rodents is infrequent or
minimal at best, and because of their small size, it is difficult to use
criteria like muscle relaxation and jaw tone to determine the depth of
anesthesia, as one does in other species.
6. Criteria for selecting anesthesia
When trying to determine the most appropriate anesthetic for use on rodents, several
criteria should be considered:First, what is the purpose of the anesthesia?
The purpose will directly influence the duration of anesthesia--whether for short termrestraint in order to perform a physical exam or radiograph or for long-term generalanesthesia for a complicated protocol.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 5
Second, what is the type of experiment or procedure?
Is this a survival procedure or a non-survival procedure? With a survival procedure, it isimportant that the anesthesia has minimal adverse effects, thereby minimizing its influenceon the data being collected. For example, for a respiratory study, opioids which are known to
cause respiratory depression should be avoided.
Third, is a postoperative analgesia required?
Some anesthetics provide better postoperative analgesia than others. Consider also if theappropriate equipment is available. For example, inhalation anesthetics require equipment toadminister and an adequate method of scavenging the waste gas so personnel are protectedfrom exposure. In addition, consider both the skill and experience of the anesthetist, becausethe margin of safety varies among different types of anesthetics. In general, more technicalskill is required to administer inhalants compared with injectables. Regulation of the agentshould be taken into account since some anesthetics are controlled substances and require aDEA license for purchase.
The final criteria to consider are the costs of the agent and the delivery equipment.
7. Patient characteristics
Characteristics of the individual patient that need to be considered when selecting anesthetics
include:
Species and strain
Age, size, and sex
Physical condition
Temperament
Health (preexisting diseases)
Previous administration of other drugs
Be aware of the health status and physical condition of the patient. Of special importance is any
history of previous administration of other drugs or other disease state, which may influence the
enzyme systems that metabolize the anesthetic.
8. Physical restraint
Anesthetic induction requires some form of physical
restraint. The duration of restraint will vary with the
type of anesthetic agent being administered as well as
the route of administration. While there are a variety of
restraint devices available, it generally requires more
time to place the animal into the restraint device than
to gently hold the animal during the initial inductionphase. The important point to remember is that manual
restraint should be brief, in order to minimize stress to
the animal. When using inhalant anesthetics, the use of
an induction chamber may decrease stress, depending
on the species.
Also take a look at handling and restraint in V-9042 Rats
& Mice: Care and Management, V- 9029 Hamsters: Care
and Management, and other rodent programs.
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6 LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
METHODS OF DELIVERY
9. Methods of Delivery
This section discusses methods of anesthetic delivery and applicable
equipment. In general, anesthesia is administered to rodents by either
the parenteral route or the inhalation route.
Parenteral route Inhalation route
intraperitoneal (IP)
intramuscular (IM)
intravenous (IV)
subcutaneous (SC)
open drop delivery
precision vaporizer
10. Disadvantages of Injectables
The disadvantages to using injectable anesthetics:
Once a given dose is administered, the anesthetic cannot be
changed. The duration of anesthetic effect is patient-dependent.
There is individual variability for a given dose.
Some injectable agents are irritating and measures need to be
taken to minimize this effect
11. Dilutions Prior to administering injectable anesthetics, consider the drugvolume, the site, and any irritant properties of the drug. Becauseconcentrated agents are delivered to very small animals, the actualdrug volume may be quite small. Many agents can be diluted withphysiologic saline to at least a one to one solution (1:1) and, in somecases, one to ten (1:10).
Dilutions
decrease the chance of overdosing,
facilitate drug absorption,
minimize irritation, and
increase the accuracy of volume measurement by making sure
that a significant percentage of the compound is not left within the
"dead space" of needle and syringe.
If a very large volume of drug needs to be administered, divide the
dosage among sites or use more than one route if appropriate.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 7
12. IM Route
IM injections should be administered in a large
muscle mass, and the two most common sites used
in rodents are the thigh muscles and the epaxial
muscles located along the spine. Small gaugeneedles, 26 to 30 gauge, are generally
recommended. Large volume doses can be
administered in several IM sites and dilutions are
recommended if a compound may have irritating
properties.
IM injections in rodents may be problematic,
particularly given the small muscle mass of these
animals. Muscle damage may occur from the needle
if the animal struggles during the injection, or the
injected substance itself may cause damage due to
the volume or tissue reaction.
13. IP Route
The intraperitoneal route is probably the most
common for administering injectable agents in
rodents. The technique is relatively easy to master,
and many anesthetics which create irritation when
given IM or subcutaneously (SC) do not cause
lesions or clinical evidence of pain when given IP. In
addition, many of the published drug dosages in the
literature are formulated for IP delivery. This photo
shows the proper site for IP injections in the lower
left abdominal quadrant with the animal's head in a
down position which allows gravity to move
abdominal viscera away from the injection site (drug
volumes in needles are for demonstration purposes
only). Depending on the size of the animal, a 20 to
23 gauge needle is recommended. It is also
important that the needle is long enough to span the
thickness of the abdominal wall and actually
penetrate into the abdominal space.
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14. IV Route
Intravenous administration of anesthetics is not
commonly used in rodents, because access to
peripheral vessels is limited, and the techniques are
difficult. In rats, mice, and gerbils, the lateral tailvein is the peripheral vessel most easily accessed.
To facilitate access, the vein can be vasodilated by
heating, for example, in warm water. In guinea pigs
and hamsters, the ear vein, dorsal metatarsal vein,
and the pubic or penile vein are the only accessible
peripheral vessels. In general though, these require
marked restraint and are not practical for induction
of anesthesia. However, they could be used to
administer compounds in a previously anesthetized
animal.
15. Recommendations for IV administration
There are some general recommendation for IV administration of
anesthetic agents in rodents because the vessels involved are very
small.
These include:
using small gauge needles and small gauge catheters (26 to 30
gauge),
injecting materials slowly and
stabilizing the needle or catheter once it is in place.
After an injection is completed, digital pressure is used to aid in
hemostasis. These recommendations are vital to decrease potentially
painful sequelae and to preserve vessels if the animal is part of a
chronic study.
16. Inhalant anesthetics- advantages
Inhalation anesthesia involves delivery of a volatile anesthetic agent to
the patient via the respiratory tract.
Advantages of using inhalants:
Increased control over depth as well as duration of anesthesia.
Increased safety and survivability.
Minimal metabolism, biotransformation and excretion compared with
injectables, which is desirable in a toxicology studies. Animals generally wake up faster from inhalant administration requiring
less patient support during the postoperative recovery phase.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 9
17. Inhalant anesthetics- disadvantages
Most of the disadvantages associated with inhalants
involve the required technical skills and the expense of
specialty equipment. In addition, an appropriate
scavenging system is needed to protect personnel and
to comply with OSHA regulations and requirements.
18. Open Drop-bell jar
There are two methods of inhalation anesthesia: open drop and
precision vaporizer. A transparent bell jar is used in an open drop
delivery system with the anesthetic gas placed on cotton balls or
sterile gauze at the bottom of the jar and covered with a wire screen
mesh. The mesh separates animals from contact with the anestheticand prevents irritation, and the transparency allows easy
observation of the animals. The open drop system does not permit
control over the concentration of anesthetic within the jar, therefore
only gases with low vapor pressure such as methoxyflurane should
be used. The jar must be placed in a well ventilated fume hood
whenever it is opened to protect personnel from exposure to the
anesthetic gas.
19. Vaporizer
If gases with high vapor pressure are used, for
example halothane or isoflurane, a calibrated vaporizer
must be used to control the concentration of
anesthetic. A rodent is placed in an induction chamber
connected to the vaporizer. Once the animal is
anesthetized, it can be removed from the chamber and
maintained on anesthetic gas for the remainder of the
procedure. Maintenance is most commonly done by
means of a face mask. Face or head masks are
commercially available, but are also easily made froma funnel or the proximal end of a 20, 50, or 60 cc
syringe barrel depending on the size of the rodent.
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20. Endotracheal intubation
Use of a facemask is probably the most common
means of delivering anesthetic gas to rodents;
however, it is possible to use endotracheal intubation.
In rodents, endotracheal intubation is most easily
accomplished by direct visualization of pharyngealand laryngeal structures. This can be accomplished
by using a pediatric laryngoscope with a Wisconsin
size 0 blade, filed down to make it narrower, and a
fiberoptic light or penlight for a light source. Another
option is to use a functioning otoscope which serves
as both a light source and a speculum and has the
added advantage of magnification. Endotracheal
tubes can be fabricated using intravenous over-the-
needle catheters. Catheter sizes range from 14 to 20
gauge depending on the size of the rodent being
intubated, and the tip should be blunted to prevent
trauma.
Respirators specifically designed for ventilation of
rodents are available.
21. Inhalation setup with scavenging system
An appropriate scavenging system is a crucial
part of administering inhalation anesthetics to
rodents.
A calibrated vaporizer feeds anesthetic gas into
an inhalation chamber. Attached to the opposite
side of the inhalation chamber is a facemask, and
beside the facemask is a vacuum-scavenge unit.
Another option is a carbon-filter gas scavenge
canister.
22. Parallel tube scavenging
An alternative scavenging system is to tape two
parallel tubes on either side of a funnel facemask. Thetubes are connected to a vacuum system and a
rodent's nose is placed in the cone. Any escaping
gases would be suctioned away by the parallel tubes
and protect the surgeon and other personnel in the
area from exposure to the anesthetic.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 11
INJECTABLE ANESTHETIC AGENTS
23. Scavenging options
In summary, it is necessary to provide adequate
scavenging of the volatile gases when using
inhalation anesthesia. The options addressed inthis program include use of a fume hood,
anesthesia machine scavenging, counter sweeps,
and parallel face mask suction.
24. Hypothermia
Hypothermia has been described as an adequate anesthetic for short procedures in neonatal
rodents. The neonate is encased in a latex sleeve and immersed up to the shoulders in an ice-water slurry for 3 to 4 minutes. After the procedure, the neonate is rewarmed in an incubator at
about 33 degrees. (Dannemann and Mandrell)
25. Injectable anesthetic agents
There are numerous injectable anesthetics available for use in rodents. Some of the more
popular agents include:
pentobarbital
ketamine
tribromoethanol
26. Pentobarbital
Pentobarbital is a barbiturate and, historically, the most commonly used anesthetic in rodents. An
advantage of pentobarbital is that, at recommended doses, it causes minimal cardiovascular
depression. It is also relatively long acting and can provide approximately 45 minutes of surgical
anesthesia.
There are, however, disadvantages to the use of pentobarbital. Pentobarbital
is a potent inducer of the hepatic microsomal enzyme system.
causes pronounced respiratory depression as well as hypothermia, particularly when
repeated doses are given.
has prolonged anesthetic recovery which may be accompanied by excitement.
is a controlled substance, which requires a DEA license for purchase and appropriate
record keeping and storage. is a poor analgesic in many species and can cause high mortality in hamsters and gerbils
because the margin of safety is narrow in these species.
Even thought the list of disadvantages appears long, by being aware of them, one can
successfully use this drug in rodent anesthesia
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27. Tribromoethanol
In most rodents, tribromoethanol produces good surgical anesthesia, with good skeletal muscle
relaxation and only a moderate degree of respiratory depression. It is relatively inexpensive and
not a controlled agent.
The major disadvantage of tribromoethanol is a potential for causing peritonitis. When exposed to
either light or temperatures >40C, tribromoethanol degrades into two byproducts: hydrobromicacid and dibromoacetaldehyde. Both of these compounds are highly irritating when administered
IP and result in peritonitis and visceral adhesions which may be fatal.
If prepared correctly, stored at appropriate temperatures, and kept in light-resistant bottles,
tribromoethanol can be used successfully (Kohn).
28. Urethane
Urethane produces long lasting anesthesia with rapid onset following IP administration. It has
minimal effects on the cardiovascular and respiratory systems. Urethane provides good analgesia
as well as excellent muscle relaxation.
Disadvantages to using urethane:
At high doses, hypotension, hypothermia, bradycardia, and metabolic acidosis are seen.
It is absorbed through the skin and, following topical administration to rodents, can
produce sedation and ataxia.
It is a proven carcinogen and mutagen in rodents.
If urethane is selected as an anesthetic, personnel must take precautions to adequately protect
themselves while mixing a urethane solution. Proper protection should include a double set of
gloves, face mask, and mixing under chemical fume hood. Urethane is not recommended for
survival procedures.
29. Chloral hydrate
Chloral hydrate is a hypnotic and a sedative that, at a
high dose (in the range of 450 ml/kg), gives excellent
analgesia.
Unfortunately, along with this excellent analgesia at
high dose, there is uncompensated metabolic acidosis,
hypotension, and bradycardia, as well as severe
hypothermia. In order to get good analgesia, the dose
is such that there is a very narrow margin of safety with
a dangerously deep plane of anesthesia and a
potential for significant mortality. The abdominal
viscera of this rat demonstrates the distension of
adynamic ileus, a sequela to a high concentration
injection of chloral hydrate administered IP. Chloral
hydrate also has the potential for causing peritonitis,
however, with dilute concentrations, this complication
can be avoided.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 13
30. Alpha chloralose Alpha chloralose is another agent that is a hypnotic and a sedative.
Historically it has been popularized for its lack of baroreceptor
depression which produces a stable, physiologically awake animal that
is immobilized and appears anesthetized.
A disadvantage of alpha chloralose is that it produces a slow onset ofsedation rather than a surgical plane of anesthesia. This sedation is
characterized by myoclonia, hyperacusia, persistent muscle tone,
convulsion, mild hypothermia, and acidosis. Thus, this drug is probably
a hypnotic rather than a true anesthetic and has unproved analgesic
potency in rodents.
Commonly this agent is used in the second phase of a two-phase
procedure. In the first phase, an initial surgery is performed with a
potent short-acting anesthetic. In the second phase, alpha chloralose
is used to maintain long term immobilization for nonstimulating or
nonpainful procedures.
31. Ketamine hydrochloride
Ketamine hydrochloride, a dissociative anesthetic, disrupts pain
transmission and suppresses spinal cord activity with some action at
opioid receptors. Visceral pain is not abolished with dissociative
anesthetics, and there is poor muscle relaxation and analgesia.
Ketamine is a poor anesthetic when used alone, but is more often
combined with other agents. When combined with other drugs, it is
usually administered IP.
Ketamine is acidic, can be irritating, and cause muscle necrosis when
administrated IM. Ketamine-induced nerve damage can cause self-
mutilation in rodents.Ketamine is a controlled substance. Store in a locked cabinet and
maintain a log of its use.
32. Ketamine + xylazine
Drugs often used in combination with ketamine are xylazine,
acepromazine, and diazepam. The ketamine/xylazine combination
offers superior analgesic activity and is the combination most
frequently used. Advantages of ketamine/xylazine include rapid
induction with a relatively long duration (60 to 90 min.) of anesthesia
plus good analgesia. Upon initial administration, there is transient
respiratory and cardiovascular depression. There is also excellent
muscle relaxation, and both the induction and recovery phase aresmooth. In general, ketamine/xylazine is administered IP in most
rodents.
The ketamine/xylazine combination, particularly at high doses, can
cause significant hypothermia and appropriate measures should be
taken to minimize this disadvantage. This combination can also
increase intraocular pressure,
result in hyperglycemia due to an increase in hepatic glucose
production and a decrease in insulin,
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14 LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
and also decrease gastrointestinal motility.
33. Yohimbine
Yohimbine is a central alpha-2 adrenergic receptor antagonist that can
be used to reverse central nervous system (CNS) depression,
sedation, bradycardia, and respiratory depression caused by xylazine.
It works within 1-3 minutes when administered IV and within 10minutes when administered IP. Adverse effects of yohimbine are
excitement and seizures. Yohimbine is used to allow animals to
recover more quickly from the anesthetic combination of
ketamine/xylazine. However, in some cases this may not be desirable,
and it may be better to let the animals have a slow, gentle recovery.
34. Ketamine + diazepam
Ketamine/diazepam has rapid onset with about 45 to 60 minutes
duration of anesthesia. Ketamine/diazepam causes the least
respiratory and cardiovascular depression of all ketamine tranquilizer
combinations.The disadvantages of using ketamine/diazepam are
some muscle rigidity and hyperacusia at low dosages,
poor analgesia compared to ketamine/xylazine, and
a chance for significant hypothermia.
Ketamine/diazepam is selected for studies that require the least
respiratory and cardiovascular depression.
35. Tiletamine + zolazepam
A drug combination consisting of tiletamine, a dissociative anesthetic,
and zolazepam provides anesthesia suitable for restraint, blood
sampling, or minor manipulative procedures; however, it provides very
poor analgesia. At high enough doses to provide sufficient surgicalanesthesia, there are problems with prolonged recovery, severe
hypothermia, and hyperacusia. Tiletamine/zolazepam is generally not
recommended for use in rodents for surgical anesthesia.
36. Fentanyl + fluanisone
The combination of fentanyl and fluanisone is a neuroleptanalgesic.
This combination provides reliable surgical anesthesia and analgesia
with good muscle relaxation. Non-purposeful limb movements are
inhibited.
Disadvantages of the fentanyl/fluanisone combination are:
mild to moderate respiratory and cardiovascular depression,
hypothermia, and
difficult to obtain in the United States, though this combination drug
is a very popular general rodent anesthesia in Europe.
Midazolam, which is often combined with fentanyl/fluanisone, is water
soluble, non-irritating, and short acting, and provides additional
analgesia.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 15
37. Propofol
Propofol is an hypnotic agent administered IV. Typically rodents are
initially anesthetized with another agent, and long term anesthesia is
maintained by IV propofol infusion. It is considered a poor analgesic, but
offers the advantage of rapid recovery.
A disadvantage of propofol is that it requires IV infusion, limiting its use inguinea pigs, hamsters, and gerbils.
38. Local anesthetics
Local acting anesthetics, such as lidocaine, or longer-acting bupivicaine,
may be infiltrated into tissues as an adjunct to general anesthesia. Long
acting local anesthetics may reduce postoperative pain perception,
reducing need for general analgesics. Typically, a small volume of local
anesthetic is infiltrated into a tissue in the area where an incision will be
made (preemptive) or has been made.
INHALATION ANESTHETIC AGENTS
39. Inhalant agents
The following discussion covers inhalant anesthetic agents which include:
halothane
isoflurane
methoxyflurane
carbon dioxide
40. Halothane
Halothane is readily available, a potent anesthetic, and not flammable or
explosive. It has more rapid induction and recovery compared to ether
(generally discouraged as an explosive hazard) and methoxyflurane.
Some disadvantages are that halothane:
reduces cardiac output.
causes peripheral vasodilation leading to hypotension or low blood
pressure.
is a dose-dependent respiratory depressant.
Halothane requires some hepatic metabolism in order to be excreted and
has been shown to be hepatotoxic to guinea pigs with repeated use.
Halothane must be scavenged as it can cause epinephrine-related
cardiac arrhythmias.
41. Isoflurane Isoflurane is nonflammable and nonexplosive. Comparedto halothane, isoflurane causes
less depression of cardiopulmonary function.
less sensitization of the heart to catecholamine (beta-adrenoceptor
agonist) release.
less profound respiratory depressant effect.
Note that isoflurane reduces renal blood flow, glomerular filtration rate
and urinary flow. It is not a significant hepatotoxin. Isoflurane's
metabolism to organic and inorganic flourides is less than any other
halogenated agent available, so if a minimally metabolized anesthetic is
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needed, isoflurane is the choice. Both induction and recovery from
isoflurane are rapid.
42. Methoxyflurane Methoxyflurane has recently become unavailable in the United States,
but is covered here since it is still available elsewhere. Methoxyflurane is
nonflammable, nonexplosive, and a potent analgesic. Low vaporpressuremakes it the only agent suitable for the open drop method. A
disadvantage of methoxyflurane, compared to other inhalents, is a
relatively slow induction phase that can result in a modest respiratory
and cardiovascular depression. Perhaps the biggest disadvantage is that
metabolization leads to flouride ion release which is nephrotoxic. An
appropriate scavaging system must be in place to protect personnel.
43. Carbon dioxide The utility and humane acceptability of CO2 and O2 combination as an
anesthetic is an area of contention. This combination is used for
extremely short term procedures.
Some studies have found that low concentrations (50% CO2) lead to
prolonged induction and severe and frequent adverse effects that includenasal bleeding, excessive salivation, seizures, and even death. Humans,
when asked to voluntarily breath 50% CO2, rated the experience as
unpleasant.
High CO2 concentrations (100%) produce rapid anesthesia with few
adverse effects, but when humans were asked to breathe 100% CO2,
they reported that this experience was extremely painful. A
recommendation is to provide CO2 in the ratio of 70% CO2 to 30% O2 for
anesthesia, as a compromise of humane acceptability and practicality
(Kohn).
MONITORING
44. Anesthetic depth
Throughout the course of anesthesia, animals should be observed for
pink mucous membrane color, a general indication of aqequate
oxygenation. Respiratory rate should remain even. Movement or change
in respiratory rate or depth in response to manipulation may indicate
insufficient depth of anesthesia. Confirm the animal's lack of response to
stimulation, such as withdrawal from a paw pinch, every 15 minutes or so
throughout a surgical procedure.
Pulse oximetry can be used as an objective measure of oxygen
saturation and pulse rate. Several units are available that can be used
with rodents such as rats. However, small size and lack of a tail in some
species limit sites for sensor application.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 17
ANALGESIA
45. Assessment of pain
Pain in rodents is most commonly assessed on the basis of subjective
measures and observations combined with professional judgment.
Clinical assessments of pain include behavioral changes such asimmobility, unkempt appearance, lack of appetite, abnormal vocalization,
and abnormal posture.
Animals experiencing pain may appear
unresponsive
lethargic
anxious
apprehensive
hypersensitive
aggressive
Any single measure is not pathognomonic for pain. Porphyrin tear
staining may be noted in rats. Animals may chew on themselves or pullhair.
Physiologic signs such as pupil dilatation, fluctuations in blood pressure,
increased heart rate, respiratory rate, and body temperature may be
more difficult to routinely assess. Implanted telemetry devices are used
in some situations to provide objective data on some of these
parameters. Changes in weight can be readily measured.
When pain or distress is suspected, humane considerations dictate that
relief be provided to an animal.
46. Herd analgesia
Rather than assessing individual animals for signs of discomfort,
investigators mayprospectively design an analgesic protocolwhich will
make postoperative analgesic therapy available to each study
participant. The strategies involve recognizing and eliminating pain in
groups of rodents, rather like a herd approach to analgesia. In this
approach, the pain intensity of a given research procedure, based upon
known discomfort levels in larger companion animal species or humans,
should be considered. The prediction of pain intensity is often based on
the type of procedure and the location of the lesion. (Kohn)
47. Salicylates Acetylsalicylic acid (aspirin) and sodium salicylate are
used to relieve only mild to moderate pain; they do not relieve deep-seated visceral pain or sharp intense pain. Aspirin is not routinely
administered to rodents because of the difficulty in dissolving the drug in
water or other oral solutions.
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48. Morphine-sulfate
Morphine-sulfate is a potent narcotic analgesic. It is a controlled
drug and must be stored in a locked cabinet and a log of use
maintained. Investigators need to be aware that animals will
develop tolerance to morphine with chronic administration.
Morphine has a short duration of action and must be re-
administered at frequent intervals usually of less than 4 hours.Morphine can induce respiratory depression and sedation.
49. Meperidine
Meperidine is a narcotic sedative and analgesic that is less
potent than morphine. It can be used as a postoperative
analgesic and its respiratory depressant effects are similar to
morphine. An advantage is the effects can be reversed by an
antagonist. Effects of meperidine are short lived, usually about 4
hours.
Like morphine, meperidine is a controlled drug. Since it is not as
potent as morphine, there is no particular advantage to using itinstead of morphine when a potent, short-acting analgesic is
indicated.
50. Buprenorphine
Buprenorphine is an opioid with prolonged duration of
action, ranging from 6 to 12 hours. High dosages can
negate the analgesic effect, and complications from
repeat high dosage include hematuria and GI bleeding.
(This photo shows hemorrhage in the bladder of a rat
given repeat high dose buprenorphine.) At lower doses
buprenorphine is an effective analgesic in rodents.
(Liles, Flecknell, Roughan, and Cruz-Madorran)
51. Other analgesics
Use of other analgesics has been described. Analgesics with less utility
in rodents include pentazocine, butorphanol, flunixin meglumine, and
nalbuphine.
Pentazocine lactate is a nonnarcotic analgesic used in postsurgicalcare. The respiratory depressant effects of pentazocine areconsidered less than those of meperidine, but unfortunately, it doesnot work well in rats.
Butorphanol tartrate is a synthetic analgesic with narcoticagonist/antagonist properties. In humans, it is three to five timesmore potent than morphine. Unfortunately, it lacks potency inrodents.
Flunixin meglumine is an agent that is used commonly in humansand dogs. It is a potent non-narcotic, nonsteroidal analgesic agentwith anti-inflammatory and antipyretic activity. Again, it is not usefulin rodents-often resulting in a hyperexcitable animal.
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 19
Nalbuphine is a mixed synthetic narcotic agonist/antagonistanalgesic related to oxymorphone and naloxone. However, its veryshort duration time of minutes in rodents makes it useless in rodentanalgesia.
52. Analgesics -preemptive
Preemptive analgesia is the administration of analgesic agents prior to or
at the time of anesthesia, before any tissue-damaging procedures, such
as incisions, have been started. Preempting pain signals in this way have
been shown, in humans, to decrease levels of postoperative pain and
need for analgesia. Preemptive administration of analgesics such as
buprenorphine has also been shown to decrease the amount of
isoflurane gas anesthetic needed to maintain a surgical plane of
anesthesia in rats (Criado).
53. Analgesics -oral
There is no assurance that oral formulations of analgesics, regardless of
flavor or formulation chosen, will be voluntarily ingested by a given
rodent in sufficient quantity to provide effective analgesia. However,
administration of oral buprenorphine mixed with flavored gelatin has
been described as an effective analgesic in rats. The rats are
preconditioned to take flavored gelatin as a treat. (Flecknell, Roughan and
Stewart)
For doses, refer to the Formulary for laboratory animals (Hawk and Leary),
Anesthesia and analgesia in laboratory animals (Kohn, Wixson, White and
Benson), orResearch animal anesthesia, analgesia and surgery(Smith
and Swindle).
54. Supportive care
Intra- and post-surgical supportive care includes
ocular lubrication, topical antibiotics, nutritional
considerations, and minimizing heat loss.
Rodents typically are not fasted or water restricted
prior to anesthesia, as is done with larger species.
Typical postoperative nutritional support can
include supplemental fluids to maintain fluid
volume.
One may also provide
warmed 5% dextrose, given SC
gelatin or agar diets, as well as fruit or
vegetables or peanut butter.
Use of fresh fruit or vegetables may be restricted in some facilities.
Ocular lubrication during the entire anesthetic episode, as well as into
the postoperative phase is recommended Antibiotics should be used
when appropriate, including the use of topical antibiotics along implant
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20 LABORATORY ANIMAL MEDICINE AND SCIENCE - SERIES II
exit sites. Antibiotic use should not be a routine antidote for poor intra-
operative sterile technique.
Care should be taken to minimize heat loss to the environment. This can
be done by using a heated OR table, heat blankets, heat lamps, drapes,
and minimizing organ exposure from body cavities. While animals are
recovering from anesthesia, rodents may huddle with cage-mates forwarmth. However, anesthetized rodents should not be caged with awake
animals. Return each animal to group housing only when confidant the
animal is able to move about and defend itself.
The V-9055 Rodent Surgery program contains a thorough discussion of
supportive care.
54. ACLAM Credits
The Laboratory Animal Medicine and Science _ Series II
has been developed under the following committee for the
American College of Laboratory Animal Medicine
C. W. McPherson, DVM, ChairJ. E. Harkness, DVM
J. F. Harwell, Jr., DVM
J. M. Linn, DVM
A. F. Moreland, DVM
G. L. Van Hoosier, Jr., DVM
L. Dahm, MS.
59. HSCER Credits
Produced by the
Health Sciences Center for Educational Resources,
University of Washington,
Seattle WA 98195
2000
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V-9054 Lab Animal Medicine: Rodent Anesthesia & Analgesia 21
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