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INTRODUCTION
Anesthesia and Analgesia
GUIDELINES and REGULATIONS
Guidance on the use of anesthetics, analgesics, and other categories of drugs for the prevention
or relief of pain and distress in laboratory animals comes from several documents. Appropriate parts of
those documents are listed below.
The U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in
Testing, Research and Training states the following: "Proper use of animals, including the avoidance or
the minimization of discomfort, distress, and pain when consistent with sound scientific practices, is
imperative. Unless the contrary is established, investigators should consider that procedures that cause
pain or distress in human beings may cause pain or distress in other animals." Additionally,
"Procedures with animals that may cause more than momentary or light pain or distress should be
performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures
should not be performed on unanesthetized animals paralyzed by chemical agents."
The Guide for the Care and Use of Laboratory Animals (1996 ed.) states the following: “The
proper use of anesthetics and analgesics in research animals is an ethical and scientific imperative.” “In
general, unless the contrary is known or established, it should be assumed that procedures that cause
pain in humans also cause pain in animals.” If a painful procedure must be conducted without the use of
an anesthetic, analgesic, or tranquilizer, because such would defeat the purpose of an experiment, the
procedure must be approved by the Institutional Animal Care and Use Committee (IACUC).
Neuromuscular blocking agents (e.g., succinylcholine, pancuronium) are not anesthetics. They must not
be used alone for surgical restraint, although they can be used in “properly ventilated conscious animals
for specific types of nonpainful, well-controlled neurophysiologic studies.”
Last, but certainly not least, the Animal Welfare Act (Public Law 89-544) as amended, requires
that institutional veterinarians provide guidelines regarding the use of tranquilizers, anesthetics,
analgesics, and euthanasia agents. In the case of a research facility, the program of adequate veterinary
care shall include “the appropriate use of anesthetic, analgesic, or tranquilizing drugs...”
Anesthesia is the act of providing sensation-free relief from pain or pain-producing procedures.
Anesthesia must be performed by a person with knowledge of and familiarity with the drugs to be used in
the animal species under consideration. It is the responsibility of the Principal Investigator to ensure
adherence to proper procedures during the execution of the protocol. Investigators may arrange training
for their technicians by contacting the Division of Laboratory Animal Resources (DLAR) (323-5885) or
the Office of the University Veterinarian (257-2549).
Definitions:


Neuroleptic - produce central nervous depression, depression of excitability of the autonomic
nervous system, a dulling of consciousness and a reduction of spontaneous motor activity.
Analgesia - relief from pain

Preemptive analgesia – managing pain before it begins

Tranquilization - a state of behavioral change in which the patient is relaxed, unconcerned by its
surroundings, and often, indifferent to minor pain.

Sedation - a mild degree of central depression in which the patient is awake but calm; larger
doses of sedative may lead to narcosis.

Narcosis - a drug-induced state of sedation in which the patient is oblivious to pain.

Local anesthesia - loss of sensation in a limited body area.

Regional anesthesia - insensibility in a larger, though limited, body area.

Basal anesthesia - a light level of general anesthesia usually produced by preanesthetic agents. It
serves as a basis for deeper anesthesia on administration of other agents.

General anesthesia - complete unconsciousness surgery can be performed painlessly and without
struggle on the part of the patient.

Neuroleptanalgesia - a state of central nervous system depression and analgesia usually produced
by a combination of a neuroleptic and a narcotic analgesic.
Factors Affecting Choice of Anesthetic and Analgesic Regimens
Dosage charts for anesthetic and analgesic agents state only the average amount of drug that
would be expected to produce a desired level of anesthesia or analgesia under standard conditions.
Consequently, animals must be monitored carefully and the dosages tailored to meet each clinical and
research situation. The DLAR veterinarian(s) are available for consultation on the selection of the best
agent and dosage to meet specific research needs.
Many factors can affect the activity of anesthetics. The species, strain, sex, age, physiologic
status, relative body size, disposition/demeanor, presence of concurrent pain or distress, or medication
are known to cause a variation in the amount of drug needed to produce a desired effect in an individual
animal.
Numerous studies have shown that preemptive analgesia, managing pain before it begins, holds
significant benefits for the animal. If the selected analgesic does not interfere with the research
parameters, the quality of the data produced by use of the animal can be improved when the stress
secondary to pain is removed. Analgesia is more effective when given before a painful procedure is
introduced, and preemptive analgesia should be used whenever possible.
The duration of anesthesia produced by the anesthetic should coincide with the expected duration
of the operative procedure. The duration of analgesia produced by the analgesic should coincide with the
expected duration and intensity of post-operative pain generated by the procedure. The time required for
post-surgical recovery from anesthesia, as well as the frequency of administration of analgesics should
coincide with the level of post-surgical care that is available. Knowledge, experience and skill with
available agents and equipment can affect the outcome of the use of anesthetics and analgesics.
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Safety precautions would include the protection of humans from vapors of volatile anesthetics.
This is best accomplished by the use of an approved gas scavenging system, or by using the volatile
anesthetic agent inside an approved fume hood.
Many of the drugs described in this section have the potential for human abuse. Therefore, they
must be maintained in a manner that is in compliance with all federal laws and requirements for the
handling and storage of controlled substances. Drugs that are subject to control under the Drug
Enforcement Agency (DEA) must be stored in a locked cabinet.
Controlled Substance
Public Law 91-513, Section 202:
"There are five schedules of controlled substances, to be known as schedules I, II, III, IV, and V."
Oversight for compliance with the law resides with the Drug Enforcement Agency (DEA).
Schedule I - "The substances in this schedule are those that have no accepted medical use in the United
States and have a high abuse potential."
Schedule II - "The substances in this schedule have a high abuse potential with severe physic or physical
dependence liability. Schedule II controlled substances consist of certain narcotic, stimulant and
depressant drugs."
Schedule III -"The substances in this schedule have an abuse potential less than those in Schedules I and
II, and include compounds containing limited quantities of certain narcotic drugs and non-narcotic
drugs..."
Schedule IV- "The substances in this schedule have an abuse potential less than those listed in Schedule
III..."
Schedule V - "The substances in this schedule have an abuse potential less than those listed in Schedule
IV and consist primarily of preparations containing limited quantities of certain narcotic and stimulant
drugs..."
Record Keeping Requirements:
A written record is required when any DEA controlled substances are used. The record should
reflect the purchase/acquisition date of each drug, the volume received, the date and volume of each use
of the drug, and the volume of drug remaining in the inventory. Each entry in the record should be
signed by the person authorized to dispense the drug.
Individual animal clinical records should be annotated to reflect the use of the agents described
above, showing the date and dose. All records should be stored in such a way that they are readily
available for review by members of the IACUC, by authorized inspectors from the Office of Laboratory
Animal Welfare (OLAW), the DEA, and/or the U.S. Department of Agriculture.
Pretreatment of the Surgical Patient:
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Drugs such as anticholinergics, tranquilizers, or sedatives are given as anesthetic pretreatment for
a variety of reasons. The primary goal of pretreatment with the majority of these agents is to minimize
anxiety or excitement of the patient. Some drugs may be used to ease the transition to the first plane(s)
of anesthesia, to decrease the amount of anesthetic agent, to prevent vomiting, or to control secretions.
Anticholinergic: (e.g., atropine sulfate, glycopyrrolate)
These agents block parasympathetic impulses to the cardiopulmonary system, glands and smooth
muscle. Consequently, they prevent vasovagal reflexes, with concurrent slowing of the heart, and reduce
salivary gland and bronchial secretions. The effectiveness of atropine varies among species.
Tranquilizers/Sedatives:
(Tranquilizers = phenothiazines [e.g., acepromazine] and butyrophenones [e.g., droperidol and
azaperone]) (Sedatives = barbiturates, benzodiazepines [e.g., diazepam, zolazepam]).
The distinction between tranquilizers and sedatives is mainly semantic. One differentiating
characteristic, however, is that tranquilizers at high dose levels tend to produce side effects without a loss
of consciousness. Sedatives at high dose levels cause a profound CNS depression that resembles
anesthesia. Tranquilizers calm the animal, facilitate handling for anesthetic induction, and reduce the
amount of anesthetic required for induction and maintenance of general anesthesia, thereby decreasing
the undesirable side-effects of the anesthetic agent. Tranquilizers also may enhance smooth anesthetic
recoveries (usually in conjunction with analgesics). Tranquilized animals can be readily aroused by
painful stimulation because tranquilizers do not produce analgesia.
Tranquilizers can, in some settings, provide skeletal muscle relaxation when the relaxation
produced by the anesthetic agent is insufficient. This effect may be observed in rabbits and cats with the
administration of a combination of acetylpromazine and ketamine hydrochloride. This activity is not as
pronounced, however, as the skeletal muscle relaxation which results from the administration of
neuromuscular blocking agents (e.g. succinylcholine).
Sedatives produce a mild degree of central nervous system (CNS) depression in which the animal
is conscious but calm and not nervous. These agents will produce a psychological calming of an animal
but do not exert hypnotic or analgesic effects. Animals can become aroused and can react to painful
procedures.
Loud noise stimulation can reverse the calming effects of these drugs. When used as
preanesthetics, ample time should be allowed for the drug to reach its maximum effect, before attempting
to induce anesthesia. All tranquilizers and sedatives share many of the described characteristics, but each
drug has its own diverse pharmacologic properties, along with contraindications.
Alpha2-Adrenergic Agonists: ( e.g., xylazine, detomidine, medetomidine)
This class of drugs mediates analgesia, anxiolysis, sedation, sympatholysis, and control of
hypertension. These drugs are usually classified as sedative-analgesics and skeletal muscle relaxants.
There is wide species variation in the reaction to these drugs. Xylazine sedation may be reversed using
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yohimbine, tolazoline, or idazoxan. Atipamezole is a highly selective and potent 2-antagonist that
rapidly reverses sedation as well as other behavioral and physiologic effects of medetomidine.
Nonchemical pretreatment:
Nonchemical pretreatment procedures, such as withholding food prior to surgery, are advisable
to prevent regurgitation of stomach contents and aspiration into the respiratory tract while the animal is
anesthetized.
General Anesthetics:
Anesthetics produce, in a controllable manner, both loss of consciousness and an absence of
motor response to noxious stimuli. This unconsciousness, analgesia, and muscle relaxation should be
sufficient to allow the performance of painful procedures without the subject experiencing pain.
Animals should be in good health before the administration an anesthetic agent. The animal's
physical condition should be evaluated to assure that there are no disease conditions that may
compromise the well being of the animal during anesthesia.
The level of anesthesia should be limited to the induction of the minimal degree of CNS
depression necessary for performing the procedure. When an injectable anesthetic agent is used, drug
dose calculation should be based on body weight and age. Because of the wide variation within and
among species, there is really no such thing as a predetermined anesthetic dose. General anesthesia must
be given "to effect," as noted in physiologic responses and in response to noxious stimuli. It is important
to realize that some drugs take time to take effect. Many anesthetic deaths can be attributed to giving the
anesthetic insufficient time to work. This is especially true of parenterally administered drugs (e.g.,
barbiturates) - once they are injected, there is little the anesthetist can do to control the outcome.
To avoid hypothermia, body temperature should be monitored and maintained throughout the
anesthetic process. Conservation of body heat is an integral part of anesthetic management. Especially
in small animals, core body temperature can fall precipitously during general anesthesia. Hypothermia,
when added to other factors, can produce an irreversible sequence of events leading to death. To avoid
thermal burns, water heating pads rather than electrical pads, should be used.
During lengthy procedures, anesthetized animals may become dehydrated. To help maintain
normal hemodynamics, warm, balanced electrolyte solutions should be administered, by continuous
intravenous drip, throughout the surgical procedure. Rodents may be administered fluids via the
subcutaneous route.
The anesthetist's responsibility for the animal’s welfare extends beyond the completion of the
surgical procedure. Continuous monitoring by a trained person should be provided until the animal is
able to maintain itself in sternal recumbency and is breathing normally. Some anesthetics and analgesics
affect animals for days after administration. Therefore, it is important to check animals daily for signs of
anorexia, fever, vomiting, or abnormal respiration or heart rate.
Stages of General Anesthesia
Stage I
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Stage of Analgesia; loss of pain without loss of consciousness or sense of touch. This stage
exists from the moment of induction to the loss of consciousness. Respiration is unchanged, and
the pupils may not change or exhibit moderate reflex dilation. Analgesia is present.
Stage II
Excitement Stage: loss of consciousness to the onset of regular respiration. In this stage, the
higher cerebral centers are depressed with loss or inhibition of the secondary centers.
Excitement and struggling may occur. This is one of the danger periods of anesthesia during
which vomiting and physical injury may take place. Therefore, the anesthetist should strive to
cause the patient to pass through this stage as quickly as possible. In order to obtain a smooth
and rapid induction, careful attention must be paid to proper and adequate premedication, proper
restraint of the animal, and minimal sensory stimuli. Respiration is irregular; there may be
periods of breath-holding. The pupils show reflex dilation. Muscular tone is increased, while
analgesia is present.
Stage III
Surgical Anesthesia: from the onset of regular respiration to the cessation of spontaneous
respiration due to central respiratory paralysis from the action of the anesthetic agent.
Plane 1 - Respiration is regular with an increase in tidal volume. There is nystagmus and
the pupils are constricted. There is a loss of the vomiting, eyelid, and pharyngeal reflexes. Small
muscle tone is lost. Although swallowing is retained in upper first plane, it is of value primarily
in recovery from anesthesia.
Plane 2 - Respiration is regular but shallower. The eyeballs are fixed (central) and the
pupil is in mid-dilation. There is a loss of the corneal, visceral, laryngeal, and cough reflexes.
The large muscles are beginning to relax in this plane.
Plane 3 - This plane is entered when there is the beginning of progressive intercostal
muscle lag, in which diaphragmatic movement precedes the action of the intercostals. It ends
with the cessation of intercostal movement. The pupil is moderately dilated and all muscle tone
(except diaphragmatic) is lost.
Plane 4 - Respiration shows complete intercostal paralysis and breathing is
diaphragmatic. Inspiration is short and gasping, with retraction of the intercostal spaces. The
pupils show paralytic dilatation.
Stage IV - begins with respiratory paralysis and progresses quickly to circulatory failure.
Pertinent notes on the signs of anesthesia
The eyelash reflex is related to the eyelid reflex. If the eyelash is stroked or the eyelid is opened,
the patient will actively attempt to close its eye in the second stage. In the third stage, the eyelid will
close passively, or will remain open, and stroking the eyelash will elicit no response.
Since swallowing will occur before vomiting when the patient is becoming “light,” the
continuous presence of the anesthetist’s hand on the patient’s chin may aid in detecting signs of
swallowing, and permit an increase in the depth of anesthesia before vomiting occurs.
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Pupillary size may be influenced by pre-anesthetic drugs, and may not be a reliable sign of
anesthetic depth. However, a widely dilated pupil, with little or no iris visible, should always cause
concern, since it may be the result of excessively deep anesthesia or hypoxia.
Evaluation of anesthetic effects:
Test pedal (toe pinch) and palpebral reflexes, and the tone of jaw and anal sphincter muscles. Reflexes
are absent and muscle tone is relaxed during surgical anesthesia.
Monitor depth and rate of respiration - increase in depth and decrease in rate signifies surgical
anesthesia.
Monitor heart rate - slowing indicates surgical anesthesia. An increase in rate during the performance
of a surgical procedure often indicates that the depth of anesthesia is not adequate and the animal is
feeling pain. A decrease of rate during surgery may signify an overdose of anesthetic.
Monitor body temperature - temperature falls during anesthesia; warming causes faster metabolism of
anesthetic agent. Maintain body temperature at normal levels, usually 37ºC, if possible
Indications of anesthetic overdose:
Heart rate - may be rapid or slow, depending on the animal's state of physiological decompensation.
Pulses - may be weak, or even imperceptible.
Blood pressure - reduced to shock level.
Cardiac dysrhythmias - may be noted.
Capillary refill time - progressively slows to 3 or more seconds.
Respiration - slow and irregular; often becomes diaphragmatic; may eventually cease.
Mucous membrane/skin colors - pale to cyanotic.
Gastrointestinal, ocular, musculoskeletal, and nervous system reflexes - greatly diminished or cease.
Interventions for anesthetic overdose:
Turn off gas anesthetics. If reversible anesthetics are on board, administer reversal agent.
Mechanically ventilate with oxygen.
Administer isotonic fluids, intravenously or intraperitoneally. Warm animal to increase body
temperature. If available, administer antidote/reversal agent.
Neuromuscular Blocking Agents (Immobilizing Drugs or Paralytics):
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Neuromuscular blocking agents inhibit the transmission of nerve impulses at the neuromuscular
junction (e.g., succinylcholine) or at spinal synapses (e.g., mephenesin, guaifenesin) resulting in skeletal
muscle paralysis and profound muscular relaxation without loss of consciousness. These agents are used
as an adjuvant in surgical anesthesia to obtain more complete muscle relaxation for specific procedures;
i.e. bone fracture repair in heavily muscled animals (horses).
Depolarizing neuromuscular blocking drugs (e.g., succinylcholine) cannot be reversed.
Competitive neuromuscular blocking agents (e.g., d-tubocurarie, pancuronium) can be reversed. These
agents produce muscle paralysis only. They do not produce sedation or analgesia. These agents should
never be used as anesthetic or analgesic agents (9 CFR 2.31: NRC. 1996: PHS. 1996).
Anesthesia is the act of providing sensation-free relief from pain or pain-producing procedures.
Anesthesia must be performed by a person with knowledge of and familiarity with the drugs to be used in
the animal species under consideration. It is the responsibility of the Principal Investigator to ensure
adherence to proper procedures during the execution of the protocol. Investigators may arrange training
for their technicians by contacting the Division of Laboratory Animal Resources (DLAR) (323-5885) or
the Office of the University Veterinarian (257-2549).
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REFERENCES
Code of Federal Regulations, Title 9 (Animals and Animal Products), Subchapter A (Animal Welfare),
Parts 1-3.
Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources,
Commission of Life Sciences, National Research Council. Washington, D.C., National Academy Press,
1996.
Public Health Service Policy on Humane Care and Use of Laboratory Animals, Office for Protection
from Research Risks, National Institutes of Health, U.S. Department of Health and Human Services.
Washington, D.C, 1996.
Principles and Practices of Veterinary Anesthesia, Short, Charles E. (ed.) Baltimore: Williams &
Wilkins, 1987
Lumb & Jones’ Veterinary Anesthesia, Thurmon, John C., Tranquilli, W.J., & Benson, G.J. (eds.) Third
Edition, Philadelphia: Lea & Febiger, 1996.
Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Hardman, Joel, G., Limbird, L.E.,
Onlinoff, O.B., et. al., (eds.) Ninth Edition, New York: McGraw-Hill, 1996.
Veterinary Pharmacology and Therapeutics, 7th ed., Adams, H. Richard (ed.), Iowa State University
Press, Ames, 1995
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ANESTHETIC NOTES
Several commonly-used anesthetics and analgesic medications are described briefly below. However,
numerous additional agents are available for use in a variety of species. Please contact a DLAR
veterinarian for additional information on drugs that are not listed. A veterinary drug formulary and a
number of anesthesia textbooks are available in the DLAR office.
Acepromazine Maleate: Acepromazine maleate (formerly acetylpromazine), a phenothiazine derivative,
is a potent neuroleptic agent with relatively low toxicity. Acepromazine induces tranquilization, muscle
relaxation, and a decrease in spontaneous activity. At high doses, sedation occurs. Preanesthetic
administration decreases the amount of general anesthetic required. Acepromazine possesses antiemetic,
anticonvulsant, antispasmodic, hypotensive, and hypothermic properties. Acepromazine will prevent or
decrease severity of the malignant hyperthermia syndrome in susceptible swine exposed to halothane.
Acepromazine potentiates opiates such as butorphanol, buprenorphine which if used in combination as a
pre-anesthetic, will provide sedation as well as preemptive analgesia.
Chloral hydrate: Chloral hydrate should not be used in species other than rodents. The IP dosage for a
surgical plane of anesthesia in rodents is 300-400 mg/kg body weight. Unfortunately, because this dosage
approaches the LD50 for this agent, dosages sufficient to provide surgical anesthesia and analgesia
approach lethality. Much lower dosages (30-35 mg/kg body wt) that are reported in the literature are
hypnotic doses and are inadequate for surgical procedures. Chloral hydrate has been reported to cause
adynamic ileus in the rat. This condition involves an accumulation of fluid and gas in the intestine and
can be avoided by using a low concentration of drug (3-4% solution, rather than a 7-8% solution).
Adverse effects include severe respiratory depression and cardiovascular and thermoregulatory
depression.
Equi-Thesin: No longer commercially available, but can be prepared in the following manner. Dissolve
8.5 mg of chloral hydrate in 20 ml 95-100% ethanol. Then add 1.96 g pentobarbital (Nembutal = 50
mg/ml) and 4.25 g MgS04. After everything else is in solution, add 60 ml propylene glycol. Bring up to
total volume of 200 ml with water (water can be added at any stage). Dose for rats is 1 ml/300 g IP.
Ether: Because of the serious hazard created by the highly flammable and explosive properties of ether,
together with the fact that satisfactory alternative inhalatant anesthetics are available (e.g., isoflurane or
halothane), use of ether as an anesthetic agent is discouraged. Because animal rooms are not equipped
with appropriate ventilation hoods, the use of ether in animal rooms, or in any DLAR space, is
prohibited. In addition, the use of ether as a euthanasia agent is restricted because of the requirement for
degassing of carcasses by storage in appropriate explosion-proof refrigerators, since ether-saturated
carcasses create an extremely serious hazard when they are incinerated.
Fentanyl Patch: Fentanyl citrate is a very potent opiate agonist. The patch is a transdermal delivery
system for the fentanyl, and it is used primarily in dogs and cats for postoperative pain, and in the control
of severe pain associated with chronic pain, dull pain, and non-specific pain (e.g., associated with
cancer). Therapeutic levels are achieved within 6-8 hours of application in the cat, while it takes at least
12 hours to reach therapeutic levels in the dog, so patch application should be performed prior to the
painful procedure, keeping these times in mind. Small dogs and cats may be dosed with ½ patch, but the
patch should NOT be cut in half. Cover ½ of the gel membrane with tape. The patch is generally placed
on the dorsal cervical area, or over the shoulders. The hair at the site should be closely clipped with at
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least a 1 cm margin around the patch. Do not shave, as cuts, abrasions or wounds can alter the absorption
of fentanyl. After clipping, wipe the skin with a damp cloth to remove small hairs and skin debris; do not
scrub or surgically prepare the site. Allow to completely dry. Place patch over the clipped area and hold
it in place for 2-3 minutes to maximize adherence. Use a slightly padded bandage or transparent dressing
used with medical adhesive spray to assure adherence and to keep it dry. Increased temperatures can
stimulate an excessive release of fentanyl from the patch, so avoid placing the patch on a heating pad.
Local anesthetic: A variety of local anesthetic agents are available and may be valuable in several types
of experimental procedures. For example, local infusion of an incision site with lidocaine may reduce
the amount of general anesthetic that is required. Application of lidocaine gel to a suture line or a cranial
implant or the use of bupivicaine to block intercostal nerves following thoracotomy, may provide
considerable pain relief.
Pentobarbital: Pentobarbital can induce severe cardiovascular and respiratory depression at doses close
to those needed to obtain a surgical level of anesthesia, often resulting in death. To reduce the likelihood
of this occurrence, pentobarbital can be administered intravenously in the following manner: calculate
the required drug volume based on a mg/kg dose and draw this volume into a syringe; administer
approximately half of the volume by rapid IV injection to achieve basal narcosis, and then slowly inject
additional incremental volumes until surgical anesthesia is achieved. The IP route of administration
should be used in rodents only.
Telazol®: Telazol® is a commercially available preparation of tiletamine (50 mg/ml) and zolezapam (50
mg/ml).
Urethane: Urethane is mutagenic and carcinogenic in rodents. Due to its numerous adverse effects, the
use of urethane is strongly discouraged unless strict precautions are taken (e.g., gloves, face masks,
mixing under a fume hood) to protect personnel. The use of urethane should be limited to nonsurvival
procedures.
Volatile anesthetics: Such agents include halothane, enflurane, isoflurane, sevoflurane, and desflurane.
These agents should be used only with adequate ventilation or scavenging systems. Precision vaporizers
must be used for these anesthetic agents because lethal concentrations can easily be reached using the
open drop method or using a bell jar as an anesthetic chamber.
Xylazine: Xylazine (Rompun®) is a centrally-acting alpha-2 adrenergic receptor agonist with analgesic
and sedative effects. Xylazine can induce profound bradycardia, decreased cardiac output, emesis and
depressed thermoregulation. Ruminants are extremely sensitive to xylazine. Yohimbine or 4aminopyridine can be used to reverse the effects of xylazine.
The following pages provide tables of drugs commonly used for preanesthesia, anesthesia,
analgesia, sedation, tranquilization, and restraint of laboratory animal species. The dosage
recommendations and other data presented on the following pages are based upon current data in the
literature, and the professional judgement of the University of Kentucky attending veterinarian(s). Doses
published in the literature are often variable. Drugs are listed for their intended use according to species.
Information on agents other than those listed may be obtained from the Division of Laboratory Animal
Resources veterinarians.
Variations in dose and duration of action will probably be observed due to factors such as animal
strain, route of administration, weight, temperament, presence of other drugs, and state of health.
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Because of these considerations, animal users must be able to judge depth of anesthesia in the individual
animal to avoid administration of a lethal dose or a dose that inadequately controls pain. Depth of
anesthesia should be monitored frequently. Response to tissue incision indicates inadequate depth.
Withdrawal response to ear pinch is a good indicator of depth in rodents and rabbits. Toe pinch and
corneal reflexes are good in carnivores.
Several additional factors should also be considered when performing surgery on animals. Food
should be withheld for 12 hours prior to anesthesia to reduce the likelihood of aspiration of gastric
material. A patent airway should be maintained during surgery, preferably by use of an endotracheal
tube. Salivation and bradycardia can be controlled by use of atropine or glycopyrrolate. Glycopyrrolate
is longer acting and should be used as a pre-anesthetic agent when known vagal stimulation will occur
during a procedure to aid in preventing, or minimizing the cardiac effects of the stimulation. Atropine
can be used to help correct bradycardia that develops during a procedure. It is faster acting then
glycopyrrolate, but it is also of shorter duration. Anesthetized animals are very prone to hypothermia.
They should be insulated from cold table surfaces and preferably should receive supplemental heat.
Temperature should be monitored every 15 minutes during anesthesia to prevent hypo-and/or
hyperthermia. Use care to avoid thermal injury from uncontrolled heat sources. If excessive blood loss
occurs during surgery, replacement fluids should be given to avoid shock.
Neuromuscular blocking agents, when used in surgical procedures, will be restricted to
anesthetized animals.
Use of any anesthetic agent must be approved by the Institutional Animal Care and Use
Committee.
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MICE
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, adequate ventilation
or scavenging system essential
Pentobarbital
35 IV
Variable response; administer to
effect
Up to 20 min. sleep time
40-70 IP
Thiopental
Tribromoethanol (Avertin)
Ketamine+Xylazine
Ketamine + Medetomidine
Chloral hydrate
Hypothermia
(neonate only)
50 IP
25 IV
125-250 IP
100 + 10 IP
75 + 1.0 IP, SC
400 IP
3-4 min
Store at 4ºC; dark conditions
Use a 5% solution
Submerge pup (to cervical area) in
water + ice; 10 min. anesthesia
ANALGESIA
Morphine
Oxymorphone
Meperidine
Imipramine
Butorphanol
(Torbutrol® 0.5mg/ml)
Buprenorphine (Buprenex®)
1-10 SC
0.05 SC
10-20 SC
2-3 SC
0.5-5 SC
3 hr
3 hr
3 hr
12 hr
6-12 hr
0.05-0.1- SC
Pentazocine
10 SC
6-12 hr; do not use with
tribromoethanol
4 hr
SEDATION
Medetomidine
30-100 g/kg SC
Ketamine
Chlorpromazine
44 SC
5-10 SC
Reverse w/atipamezole; 1 g/kg
SC, IP, or IV
NOTES
Small muscle mass: Mice have a relatively small total muscle mass and are prone to develop muscular atrophy or
nerve damage following IM injections. This route should therefore be avoided in mice. If drugs must be
administered via the IM route, minimal injection volumes (0.05 ml) should be used. Use 27-30 gauge needle.
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RATS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, adequate ventilation
or scavenging system essential
Pentobarbital
30-40 IV
40-60 IP
20-40 IV
40 IP
40-60 min. duration
60-90 + 6-9 IP
30-45 min duration; supplement
with 1/3 of ketamine dose only
Thiopental
Ketamine+Xylazine
5-10 min. duration
Ketamine + Medetomidine 75 + 0.5 IP, SC
Urethane
1000-1500 IP
Prolonged (12 hr +) anesthesia;
terminal procedure only;
carcinogenic + mutagenic
Use 5% solution; anesthetic dose
approaches LD50
Chloral Hydrate
300-400 IP
Inactin
Tiletamine-Zolazepam
(Telazol ®)
80-100 IP
20-40 IP
Methohexital
Equithesin
40 IP
3 ml/kg
1% solution; 20 min. duration
40 min. duration; fresh mixture req.
10 SC
20 SC
10 SC
10-12 SC
3 hr
3 hr
12 hr
3 hr
0.02-0.05 SC
5 SC
6-12 hr
12-24 hr
Concentration of reconstituted
mixture is 100 mg/ml
ANALGESIA
Morphine
Meperidine
Imipramine
Butorphanol
(Torbutrol® 0.5mg/ml)
Buprenorphine (Buprenex®)
Carprofen
SEDATION
Medetomidine
30-100 g/kg SC
Ketamine
50-100 IM, IP
g/kg
Reverse w/atipamezole; 1
SC, IP, or IV
NOTES
Small muscle mass: Rats have a relatively small total muscle mass and are prone to develop muscular atrophy or
nerve damage following IM injections. This route should be minimized in rats. If drugs must be administered via the
IM route, minimal injection volumes (0.3 ml) should be used. Use a 25 gauge needle (or smaller).
14
HAMSTERS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, adequate ventilation
or scavenging system essential
Pentobarbital
70-90 IP
60-75 min. duration
Ketamine + Xylazine
80-100 + 7-10 IP
Ketamine + Medetomidine
100 + 0.25 IP
Tiletamine + Zolazepam
(Telazol®) + Xylazine
20-30 IP
+ 10 IP
10-30 min. duration
Urethane
1500 IP
6 hr.
Urethane (50%) +
-Chloralose (10%) +
Pentobarbital
380 IP
38 IP
26 IP
Extend anesthesia (every 2 hr)
w/Urethane (135 mg) +
Chloralose (14 mg) IP
Carcinogenic + mutagenic
10 SC
20 SC
0.05-0.5 SC
3 hr.
3 hr.
8-12 hr.
ANALGESIA
Morphine
Meperidine
Buprenorphine (Buprenex®)
SEDATION
Chlorpromazine
Ketamine
0.5 IM
40-80 IP
15
GUINEA PIGS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, adequate ventilation
or scavenging system essential
Pentobarbital
15-40 IP
60 min. duration
Ketamine + Xylazine
40-100 + 4-5 IM
60 min. duration
Ketamine + Medetomidine
40 + 0.5 IP
Moderate anesthesia
-Chloralose (1%) +
Urethane (40%), in a 7:1
mixture
8.0 ml/kg IP
>2hr. duration
10 SC
20 IM, SC
0.05 SC
4 hr
2-3 hr
8-12 hr
ANALGESIA
Morphine
Meperidine
Buprenorphine
SEDATION
Ketamine
Chlorpromazine
Diazepam
Xylazine
40 IM
0.2 SC
2.5-5.0 IP
5-40 IP
16
RABBITS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, scavenging system
essential. Less anesthetic is
necessary, and a more even
plane of anesthesia can be
achieved if a pre-anesthetic
such as butorphanol/acepromazine
is used.
Pentobarbital
30 IV
Very narrow margin between
effective and lethal dose
Ketamine + Xylazine
35-50 + 5-10 IM
45 min., minor procedures
Supplement with 1/3 the original
dose of Ketamine+Xylazine
Ketamine + Medetomidine
25 + 0.5 IM
-Chloralose
Urethane
80-120 IV
1000 IV, IP
Equithesin
1-3 ml/kg
Carcinogenic, acute procedures
only
Fresh solutions only
2-5 SC
10 SC
0.01-0.05 SC
0.1-0.5 SC, IM, IV
1.5 SC
1 SC, IM
3 hr
2-3 hr
6-12 hr
4 hr
12-24 hr
24 hr
ANALGESIA
Morphine
Meperidine
Buprenorphine
Butorphanol
Carprofen
Ketoprofen
SEDATION
Butorphanol + Acepromazine
1 + 1 IM
Chlorpromazine
25-100 IM
Acepromazine
.75-1.0 IM
Diazepam
5-10 IM
Ketamine
30 IM
Xylazine
3-5 IM, SC
NOTES:
Anesthetic depth: Adequate anesthesia for surgery can be very difficult to obtain in rabbits, especially when
barbiturates are used. Rabbits are prone to develop respiratory depression and edema when anesthetized.
Atropinase: Atropine is frequently administered to anesthetized animals to reduce oral and respiratory secretions and
to support heart rate. Many rabbits (up to 50%) have circulating atropinase and thus may demonstrate a reduced
duration of effectiveness of this drug.
Normal values: temperature 38.5-39.0oC (101.3-102.2oF); heart rate 130-300/min; respiration rate 30-60/min.
DOGS
17
ANESTHESIA
DOSE (mg/kg) & Route
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, scavenging system
essential. Less anesthetic is
necessary, and a more even
plane of anesthesia can be
achieved if a pre-anesthetic
such as butorphanol/acepromazine
or buprenorphine/acepromazine is
used.
Pentobarbital
20- 30 IV
Give ½ as a bolus; the rest
to effect; 30-45 min. duration
Thiopental
8-12 IV
Short acting; <15 min
Chloralose
80-110 IV
6-10 hr; premedicate w/morphine
5mg/kg; terminal procedures
Ketamine + Diazepam
10 + 0.5 IV
Minor procedures; premedicate
with anticholinergic??
5.5 + 0.3 IV
Good for induction of anesthesia
after a pre-anesthetic is given, and
then maintenance of anesthesia
with a gas anesthetic such as
isoflurane.
Ketamine + Midazolam
10 + 0.5 IV
Minor procedures; premedicate
with anticholinergic ??
Tiletamine + Zolazepam
(Telazol®) + Xylazine
+ Butorphanol
6-8 IM
0.5 IM
0.2 IM
1 hr. surgical anesthesia
2-10 SC, IM
0.25-5 IM, SC
0.2-0.4 IM, SC
2-3 hr
4-6 hr
2-5 hr
0.01-0.02 SC
2.2 PO, 5 SC
2 SC, IM
See table
8-12 hr
12 hr
24 hr
Place 12 hours prior to painful
procedure. Do not apply heat to
patch area as this will stimulate a
large release of the fentanyl (watch
heating pads).
ANALGESIA
Meperidine
Morphine
Butorphanol
( Torbutrol® 0.5mg/ml)
Buprenorphine
Carprofen
Ketoprofen
Fentanyl patch
?? See above: discuss these items with a DLAR veterinarian.
Weight of Dog
Fentanyl patch size
18
Duration
< 5 kg
5-10 kg
10-20 kg
20-30
> 30 kg
½ of a 25 mcg/hr
25 mcg/hr
50 mcg/hr
75 mcg/hr
100 mcg/hr
72 hrs
72 hrs
72 hrs
72 hrs
72 hrs
SEDATION
Butorphanol + Acepromazine
0.2-0.4 SC, IM, IV +
0.02-0.05 SC, IM, IV
Buprenorphine + Acepromazine
0.07 SC, IM + 0.009 SC, IM
Xylazine
0.5-1.0 IM
Chlorpromazine
1-6 IM, SC
Acepromazine
0.05-0.1 IM, SC
Maximum of 3 mg total
NOTES:
Food: Prior to elective surgery, food should be withheld for 12 hrs.
Normal values: temperature 37.5-39oC (99.5-102.2oF); heart rate 70-120/min, respiratory rate 15-25/min.
Anticholinergic medication is recommended in anesthetized dogs to support the heart rate and reduce bronchial
secretions. Recommended agents include atropine (0.02-0.04 mg/kg SC, IM) or glycopyrrolate (0.02 mg/kg IM,
SC).
Note that the above treatment has become controversial in the field of veterinary medicine, and unless a documented
bradycardia is present, anticholinergics are not necessary and can cause a profound tachycardia. Anticholinergic
premedication is not currently recommended by veterinary anesthesiologists. Atropine is good for quick IV use if
bradycardia is present, but it doesn’t last long. If a known vagal stimulation is expected during a surgical procedure,
then glycopyrrolate is a good/better anticholinergic premedication than atropine. It will not produce as profound a
tachycardia as with atropine, and it will last longer. It does however need to be given at least 30 minutes prior to
vagal stimulation. Discuss the need for this treatment with a DLAR veterinarian.
19
CATS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Isoflurane (Forane®)
Halothane (Fluothane®)
Enflurane (Ethrane®)
To effect
Inhalation; precision vaporizer
required, scavenging system
essential. Less anesthetic is
necessary, and a more even
plane of anesthesia can be
achieved if a pre-anesthetic
such as butorphanol/acepromazine
is used.
Pentobarbital
20- 30 IV
Give ½ as a bolus; the rest
to effect; 30-45 min. duration
Ketamine + Diazepam
10 + 0.5 IV
Minor procedures; premedicate
with anticholinergic ??
5.5 + 0.3 IV
Good for induction of anesthesia
after a pre-anesthetic is given, and
then maintenance of anesthesia
with a gas anesthetic such as
isoflurane.
7 + 0.08 IM
Minor procedures; 45 min.
duration
Morphine
0.1 IM, SC
4 hr.; mania and excitation
with overdose
Meperidine
Buprenorphine
Oxymorphone
2-10 IM, SC
0. 005-0.01 SC, IM
0.05-0.15 IM, SC, or IV
Carprofen
Ketoprofen
Fentanyl patch
4 SC,d IV
1 SC, IM, IV
See table
Ketamine + Medetomidine
ANALGESIA
Weight of Cat
< 2.5 kg
> 2.5 kg
Fentanyl patch size
½ of a 25 mcg/hr
25 mcg/hr
?? See above: discuss these items with a DLAR veterinarian
20
12 hr.
3-5 hr. Minimal respiratory
depression
24 hr
24 hr
Place 8 hours prior to painful
procedure. Do not apply heat to
patch area as this will stimulate a
large release of the fentanyl (watch
heating pads.)
Duration
5 days
5 days
SEDATION
Butorphanol + Acepromazine
Ketamine
Acepromazine
Chlorpromazine
Midazolam
Diazepam
Xylazine
0.1-0.4 SC, IM, IV +
0.02-0.05 SC, IM, IV
10-20 IM
0.05-0.1 IM, SC
1-2 IM
0.2-0.4 IM
0.2-0.4 IV, IM
0.4-0.9 SC, IM
NOTES:
Acetaminophen (Tylenol) is extremely toxic in cats and should not be used in this species. Cats are also very
sensitive to the toxic effects of aspirin, and fatalities are frequently reported. Although aspirin can be used in cats,
other agents should be used if possible.
Food: Prior to elective surgery, food should be withheld for 12 hrs.
Normal values: temperature 38.0-39.5oC (100.4-103.1oF); heart rate 110-140/min; respiration rate, 20-30/min.
Anticholinergic medication is recommended in anesthetized cats to support the heart rate and reduce bronchial
secretions. Recommended agents include atropine (0.02-0.04 mg/kg SC, IM) or glycopyrrolate (0.02 mg/kg IM or
SC).
Note that the above treatment has become controversial in the field of veterinary medicine, and unless a documented
bradycardia is present, anticholinergics are not necessary and can cause a profound tachycardia. Anticholinergic
premedication is not currently recommended by veterinary anesthesiologists. Atropine is good for quick IV use if
bradycardia is present, but it doesn’t last long. If a known vagal stimulation is expected during a surgical procedure,
then glycopyrrolate is a good/better anticholinergic premedication than atropine. It will not produce as profound a
tachycardia as with atropine, and it will last longer. It does however need to be given at least 30 minutes prior to
vagal stimulation. Discuss the need for this treatment with a DLAR veterinarian.
21
NON-HUMAN PRIMATES
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Enflurane (Ethrane®)
Halothane (Fluothane®)
Isoflurane (Forane®)
To effect
Inhalation; precision
vaporizer required;
scavenging system essential
Ketamine + Medetomidine
Ketamine + Xylazine
Ketamine + Diazepam
Telazol®
2-6 + 0.03-0.06 IM
10 + 0.25 IM
10 + 0.2-0.35 IM
4-6 IM
60 min. duration
45 min. duration
Restraint + muscle relaxation
1-2 SC
2-4 IM
0. 01 IM
4 hr
3-4 hr
6-8 hr
ANALGESIA
Morphine
Meperidine
Buprenorphine
SEDATION
Ketamine
Acepromazine
Chlorpromazine
5-20 IM
1-5 IM, SC
5-10 SC, IM
ANTICHOLINERGIC
Atropine
0.02-.05 IM, SC
NOTES:
Normal values (Rhesus monkey): temperature 37.0-39.1oC (99.0-102.5oF); heart rate (sedated) 120-180/min;
respiration rate (sedated) 32-50/min.
22
PIGS
ANESTHESIA
DOSE (mg/kg) & ROUTE
COMMENTS
Enflurane (Ethrane®)
Halothane (Fluothane®)
Isoflurane (Forane®)
To effect
Inhalation; precision
vaporizer required;
scavenging system essential
Ketamine + Xylazine
Ketamine + Acepromazine
Pentobarbital
Ketamine + Telazol®
Telazol® + Xylazine
20 + 2 IM
33 + 1.1 IM
5-15 IV
2.2 + 4.4 IM
2.0-8.8 + 2.2 IM
20 min.; minor procedures
Ketamine + Medetomidine
10 + 0.08 IM
Administer to effect
20-30 min. duration
20 min. duration; may produce
cardiopulmonary depression
Immobilization; light anesthesia
10 PO
4-10 IM
10-20 PO
0.005-0.01 IM
4-6 hr.; use enteric-coated tablet
4 hr.
12 hr. For musculoskeletal pain
12 hr
ANALGESIA
Aspirin
Meperidine
Phenylbutazone
Buprenorphine
SEDATION
Acetylpromazine
Chlorpromazine
Diazepam
Azaperone (Stresnil®)
0.11-1.1 SC, IM
0.5-4 IM, SC
0.5-10 IM
2-8
Usually combined w/other agents
NOTES:
Malignant hyperthermia: Malignant hyperthermia (MH) is commonly reported in swine. The first cardinal clinical
sign of MH is an elevation in end-tidal CO2. MH characterized by the sudden onset of muscle rigidity, tachypnea,
tachycardia and hyperthermia (rectal temperatures up to 108 oF), followed by dyspnea, cardiac arrhythmias, apnea
and death. Anesthesia (particularly with halothane isoflurane, or ethrane), restraint, stress and excitement have all
been reported to trigger this condition. Anesthetized swine should be monitored closely for the development of
hyperthermia. Emergency measures include cessation of the anesthetic, cooling the body with ice water, and the IV
administration of sodium bicarbonate and the muscle relaxant dantrolene (2-10 mg/kg).
Food: Prior to elective surgery, withhold food for 12 hrs.
Normal values: temperature 38.0-40.0oC (100.4-104.0oF); heart rate 60-120/min; respiration rate 10-12/min.
Anticholinergic: Glycopyrrolate (0.004-0.01 mg/kg IM) or atropine (0.05 mg/kg IM ).
23