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http://www.mc.uky.edu/dlar/resources/sop/anes-uk.htm#Rats
Anesthesia and Analgesia
For specific topics, click on the appropriate selection:
Guidelines and
Regulations
Definitions
Controlled Substance
Record Keeping
Tranquilizers & Sedatives
General
Anesthetics
Stages of General
Anesthesia
Indications of
Overdose
Neuromuscular Blocking
Agents
References
Anesthetic Notes
Mice
Rats
Hamsters
Guinea pigs
Rabbits
Dogs
Cats
Nonhuman Primates
Pigs
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
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can be used in "properly ventilated conscious animals for specific types of nonpainful, wellcontrolled 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
Surgical anesthesia - unconsciousness, accompanied by muscular relaxation to such a degree that
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
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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.
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 nonnarcotic drugs..."
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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:
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
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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 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.
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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
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.
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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.
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.
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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):
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).
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.
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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
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
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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 1/2 patch, but the patch should NOT be cut in half. Cover 1/2 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 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 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
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output, emesis and depressed thermoregulation. Ruminants are extremely sensitive to xylazine.
Yohimbine or 4-aminopyridine can be used to reverse the effects of xylazine. However, xylazine
used is associated with a high anesthetic complication rate.
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. 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 than 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.
MICE
ANESTHESIA
Isoflurane
(Forane®)
Halothane
(Fluothane®)
DOSE (mg/kg)
& ROUTE
To effect
COMMENTS
Inhalation; precision vaporizer required;
adequate ventilation or scavenging system
essential
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Enflurane
(Ethrane®)
Pentobarbital
Thiopental
35 IV
Variable response; administer to effect
40-70 IP
Up to 20 min. sleep time
50 IP
25 IV
Tribromoethanol
(Avertin)
125-250 IP
Store at 4ºC; dark conditions
Ketamine +
Xylazine
100 + 10 IP
Ketamine +
Medetomidine
75 + 1.0 IP, SC
Chloral hydrate
400 IP
Use a 5% solution
Hypothermia
(neonate only)
3-4 min
Submerge pup (to cervical area) in water + ice;
10 min. anesthesia
Morphine
1-10 SC
3 hr
Oxymorphone
0.05 SC
3 hr
Meperidine
10-20 SC
3 hr
Imipramine
2-3 SC
12 hr
Butorphanol
(Torbutrol®
0.5mg/ml
0.5-5 SC
6-12 hr
Buprenorphine
(Buprenex®
0.05-0.1 SC
6-12 hr; do not use with tribromoethanol
Pentazocine
10 SC
4 hr
Medetomidine
30-100µg/kg
SC
Reverse w/atipamezole; 1µg/kg SC, IP, or IV
Ketamine
44 SC
Chlorpromazine
5-10 SC
ANALGESIA
SEDATION
13
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.
RATS
ANESTHESIA
DOSE (mg/kg)
& ROUTE
Isoflurane (Forane®)
To effect
Inhalation; precision vaporizer required;
adequate ventilation or scavenging system
essential
30-40 IV
40-60 min. duration
Halothane (Fluothane®)
COMMENTS
Enflurane (Ethrane®)
Pentobarbital
40-60 IP
Thiopental
20-40 IV
5-10 min. duration
40 IP
Ketamine + Xylazine
60-90 + 6-9 IP
30-45 min duration; supplement with 1/3 of
ketamine dose only
Ketamine +
Medetomidine
75 + 0.5 IP, SC
Urethane
1000-1500 IP
Prolonged (12 hr +) anesthesia; terminal
procedure only; carcinogenic + mutagenic
Chloral Hydrate
300-400 IP
Use 5% solution; anesthetic dose
approaches LD50
Inactin
80-100 IP
Tiletamine-Zolazepam
(Telazol®)
20-40 IP
Concentration of reconstituted mixture is
100 mg/ml
Methohexital
40 IP
1% solution; 20 min. duration
Equithesin
3 ml/kg
40 min. duration; fresh mixture req.
10 SC
3 hr
ANALGESIA
Morphine
14
Meperidine
20 SC
3 hr
Imipramine
10 SC
12 hr
Butorphanol
(Torbutrol® 0.5mg/ml)
10-12 SC
3 hr
Buprenorphine
(Buprenex®)
0.02-0.05 SC
6-12 hr
Carprofen
5 SC
12-24 hr
Medetomidine
30-100 µg/kg
SC
Reverse w/atipamezole; 1 µg/kg SC, IP, or
IV
Ketamine
50-100 IM, IP
SEDATION
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).
HAMSTERS
ANESTHESIA
Isoflurane (Forane®)
DOSE
(mg/kg) &
ROUTE
COMMENTS
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
20-30 IP
(Telazol®) + Xylazine
+10 IP
Urethane
1500 IP
Halothane (Fluothane®)
Enflurane (Ethrane®)
10-30 min. duration
6 hr
15
Urethane (50%) + aChloralose (10%) +
Pentobarbital
380 IP
38 IP
26 IP
Extend anesthesia (every 2 hr)
w/Urethane (135 mg) + Chlorase (14
mg) IP
Carcinogenic + mutagenic
ANALGESIA
Morphine
10 SC
3 hr
Meperidine
20 SC
3 hr
Buprenorphine (Buprenex®)
0.05-0.5 SC
8-12 hr
SEDATION
Chlorpromazine
0.5 IM
Ketamine
40-80 IP
GUINEA PIGS
DOSE
(mg/kg) &
ROUTE
ANESTHESIA
Isoflurane (Forane®)
COMMENTS
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
a-Chloralose (1%) +
Urethane (40%), in a
mixture
8.0 ml/kg IP
>2 hr duration
Morphine
10 SC
4 hr
Meperidine
20 IM, SC
2-3 hr
Buprenorphine
0.05 SC
8-12 hr
Halothane (Fluothane®)
Enflurane (Ethrane®)
7:1
ANALGESIA
16
SEDATION
Ketamine
40 IM
Chlorpromazine
0.2 SC
Diazepam
2.5-5.0 IP
Xylazine
5-40 IP
RABBITS
ANESTHESIA
Isoflurane
(Forane®)
DOSE
(mg/kg) &
ROUTE
COMMENTS
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 preanesthetic such as butorphanol/acepromazine is used.
Pentobarbital
30 IV
Very narrow margin between effective and lethal dose
Ketamine +
Xylazine
35-50 + 510 IM
45 min., minor procedures
Ketamine +
Medetomidine
25 + 0.5
IM
a-Chloralose
80-120 IV
Urethane
1000 IV, IP Carcinogenic, acute procedures only
Equithesin
1-3 ml/kg
Fresh solutions only
Morphine
2-5 SC
3 hr
Meperidine
10 SC
2-3 hr
Buprenorphine
0.01-0.05
SC
6-12 hr
Halothane
(Fluothane®)
Enflurane
(Ethrane®)
Supplement with 1/3 the
original dose of Ketamine + Xylazine
ANALGESIA
17
Butorphanol
0.1-0.5 SC,
IM, IV
4 hr
Carprofen
1.5 SC
12-24 hr
Ketoprofen
1 SC, IM
24 hr
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 3060/min.
DOGS
ANESTHESIA
Isoflurane
(Forane®)
DOSE
(mg/kg) &
ROUTE
COMMENTS
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 preanesthetic such as butorphanol/acepromazine or
buprenorphine/acepromazine is used.
20-30 IV
Give ½ as a bolus; the rest to effect; 30-45 min.
duration
Halothane
(Fluothane®)
Enflurane
(Ethrane®)
Pentobarbital
18
Thiopental
8-12 IV
Short acting; <15 min
Chloralose
80-110 IV
6-10 hr; premedicate w/morphine
procedures
Ketamine +
Diazepam
10 + 0.5
IV
5.5 + 0.3
IV
5 mg/kg; terminal
Minor procedures; premedicate with anticholinergic ??
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
6-8 IM
1 hr. surgical anesthesia
0.5 IM
(Telazol®) +
Xylazine
0.2 IM
+Butorphanol
ANALGESIA
Meperidine
2-10 SC,
IM
2-3 hr
Morphine
0.25-5 IM,
SC
4-6 hr
Butorphanol
(Torbutrol® 0.5
mg/ml)
0.2-0.4
IM, SC
2-5 hr
Buprenorphine
0.01-0.02
SC
8-12 hr
Carprofen
2.2 PO, 5
SC
12 hr
Ketoprofen
2 SC, IIM
24 hr
Fentanyl patch
See table
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).
19
Weight of Dog
< 5 kg
5-10 kg
10-20 kg
20-30 kg
> 30 kg
Fentanyl patch size
1/2 of a 25 mcg/hr
25 mcg/hr
50 mcg/hr
75 mcg/hr
100 mcg/hr
Duration
72 hrs
72 hr
72 hrs
72 hrs
72 hrs
?? See above: discuss these items with a DLAR veterinarian.
SEDATION
0.2-0.4 SC, IM, IV +
Butorphanol + Acepromazine
0.02-0.05 SC, IM, IV
Buprenorphine + Acepromazine 0.07 SC, IM + 0.0009 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.
CATS
ANESTHESIA
Isoflurane
(Forane®)
DOSE
(mg/kg) &
ROUTE
To effect
COMMENTS
Inhalation; precision vaporizer required; scavenging
system essential. Less anesthetic is necessary, and a
more even plane of anesthesia can be achieved if a pre-
20
anesthetic such as butorphanol/acepromazine is used.
Halothane
(Fluothane®)
Enflurane
(Ethrane®)
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
Ketamine +
Medetomidine
7 + 0.08 IM
Minor procedures; 45 min. duration
ANALGESIA
Morphine
0.1 IM, SC
Meperidine
2-10 IM,
SC
4 hr.; mania and excitation with overdose
Buprenorphine
0.005-0.01
SC, IM
12 hr.
Oxymorphone
0.05-0.15
IM, SC, or
IV
3-5 hr. Minimal respiratory depression
Carprofen
4 SC, IV
24 hr
Ketoprofen
1 SC, IM,
IV
24 hr
Fentanyl patch
See table
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).
Weight of Cat Fentanyl patch size Duration
< 2.5 kg
1/2 of a 25 mcg/hr 5 days
> 2.5 kg
25 mcg/hr
5 days
?? See above: discuss these items with a DLAR veterinarian.
21
SEDATION
0.1-0.4 SC, IM, IV +
Butorphanol + Acepromazine
Ketamine
Acepromazine
Chlorpromazine
Midazolam
Diazepam
Xylazine
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, 2030/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.
NON-HUMAN PRIMATES
ANESTHESIA
Enflurane (Ethrane®)
DOSE (mg/kg) &
ROUTE
COMMENTS
To effect
Inhalation; precision vaporizer required;
scavenging system essential
2-6 + 0.03-0.06
60 min. duration
Halothane (Fluothane®)
Isoflurane (Forane®)
Ketamine +
22
Medetomidine
IM
Ketamine + Xylazine
10 + 0.25 IM
45 min. duration
Ketamine + Diazepam
10 + 0.2-0.35 IM
Restraint + muscle relaxation
Telazol®
4-6 IM
ANALGESIA
Morphine
1-2 SC
4 hr
Meperidine
2-4 IM
3-4 hr
Buprenorphine
0.01 IM
6-8 hr
SEDATION
Ketamine
5-20 IM
Acepromazine
1-5 IM, SC
Chlorpromazine
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.
PIGS
ANESTHESIA
Enflurane (Ethrane®)
DOSE (mg/kg) &
ROUTE
COMMENTS
To effect
Inhalation; precision vaporizer required;
scavenging system essential
Ketamine + Xylazine
20 + 2 IM
20 min.; minor procedures
Ketamine +
Acepromazine
33 + 1.1 IM
Pentobarbital
5-15 IV
Halothane
(Fluothane®)
Isoflurane (Forane®)
Administer to effect
23
Ketamine + Telazol®
2.2 + 4.4 IM
20-30 min. duration
Telazol® + Xylazine
2.0-8.8 + 2.2 IM
20 min. duration; may produce
cardiopulmonary depression
Ketamine +
Medetomidine
10 + 0.08 IM
Immobilization; light anesthesia
ANALGESIA
Aspirin
10 PO
4-6 hr.; use enteric-coated tablet
Meperidine
4-10 IM
4 hr.
Phenylbutazone
10-20 PO
12 hr. For musculoskeletal pain
Buprenorphine
0.005-0.01 IM
12 hr.
SEDATION
Acetylpromazine
0.11-1.1 SC, IM
Chlorpromazine
0.5-4 IM, SC
Diazepam
0.5-10 IM
Azaperone
(Stresnil®)
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
108oF), 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 ).