University of Virginia Health System

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 for your information.

The U.S. Government Principles for the Utilization and Care of Vertebrate Testing, Research and Training states the following. "Proper use of animals, including the avoidance or 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 slight pain or distress should be performed with appropriate sedation, analgesia, or anesthesia. Surgical or other painful procedures should not be performed on un-anesthetized animals paralyzed by chemical agents."

The Guide for the Care and Use of Laboratory Animals, states the following: "The proper use of anesthetics, analgesics, and tranquilizers in laboratory animals is necessary for humane and scientific reasons. In accordance with the Animal Welfare Act, the choice and use of the most appropriate drugs are matters for the attending veterinarian's professional judgement. The veterinarian must provide research personnel with guidelines and advice concerning choice and use of these drugs."

"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 animal care and use committee and supervised directly by the responsible investigator."

"Muscle relaxants or paralytic drugs (e.g., succinylcholine or other curariform drugs) are not anesthetics. They must not be used alone for surgical restraint, although they can be used in conjunction with drugs known to produce adequate analgesia."

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 as follows:

1. In the case of a research facility, the program of adequate veterinary care shall include the appropriate use of anesthetic, analgesic, or tranquilizing drugs, when such would be proper in the opinion of the attending veterinarian at the research facility. The use of these three classes of drugs shall be in accordance with the currently accepted veterinary medical practice as cited in appropriate professional journals or reference guides which shall produce in the individual subject animal a high level of tranquilization, anesthesia, or analgesia consistent with the protocol or design of the experiment.

2. It shall be incumbent upon each research facility through its Animal Care Committee and/or attending veterinarian to provide guidelines and consultation to research personnel with respect to the type and amount of tranquilizers, anesthetics, or analgesics recommended for each species of animal used by that institution.

3. The use of those three classes of drugs shall effectively minimize the pain and discomfort of the animals while under experimentation.

1. Provides professional advice on the type of agents that are appropriate for use and establishes dose ranges for each.
2. Counsels the investigator on appropriate physical facilities and equipment to properly administer general anesthetics and recommends ways to monitor the physical condition of an animal while it is under treatment.
3. Provides professional expertise in response to medical emergencies if they occur.
4. Monitors surgical procedures to assess the degree of pain relief required and prescribes appropriate pain relieving drugs.

Dosage charts for anesthetic and analgesic agents usually state an amount that would be expected to produce a desired level of activity for the agent under average conditions. Consequently, these charts must be used with this principle in mind.

Another principle to remember when selecting an anesthetic or analgesic agent for use on a protocol is that there are many factors that can affect the activity of anesthetics and analgesics so they must be considered for their potential effects on activity and dose rate.

The species, strain, sex, age, physiologic status, relative body size, disposition/demeanor, presence of concurrent pain or distress, concurrent medication or other treatments are known to either increase or decrease the amount of a drug that is needed to produce a desired effect in an individual animal.

The duration of anesthesia produced by the agent should coincide with the expected duration of the experiment and the duration of analgesia produced by the analgesic should coincide with the expected level of pain generated by the experiment.

The time needed for post-surgical recovery from anesthesia and the frequency for administration of analgesics should coincide with the level of post-surgical care that is available. When personnel and resources for proper post-surgical monitoring of patients are limited, an anesthetic that has a short recovery time and an analgesic that has a long duration of activity should be selected.

Special facilities and equipment are required for the administration of volatile anesthetics and for scavenging excess gas to protect the operator. If these facilities and equipment are not available an injectable anesthetic would be the best choice.

The resins in cedar and other soft-wood bedding materials, or prior exposure to other drugs which stimulate subsets of cytochrome P450 hepatic enzymes, can alter the metabolism of anesthetics. Consequently, some other form of bedding be used to house rodents when they are to be anesthetized.

Personal knowledge, experience, preference, and skill with available agents and equipment can affect the outcome of the use of anesthetics and analgesics. These factors must be taken into consideration before the drugs are used.

Protect humans from vapors of volatile drugs such as anesthetics by connecting a gas scavenging system to anesthetic machines or by administering the agent inside a fume hood. Volatile anesthetics have been associated with spontaneous abortion, hepatic and renal toxicity, and headache in humans.

Monitor the use of chemical agents and assure that product safety recommendations are followed to protect the health and welfare of the humans and animals that are exposed to the agents

Many of the drugs described may have the potential for human abuse so they must be stored in a manner that minimizes that risk. Drugs that come under the control of the Drug Enforcement Agency (DEA) must be stored in a double locked cabinet in a secure area.

Public Law 91-513, Section 202:

There are five schedules of controlled substances, to be known as schedules I, II, III, IV, and V. Such schedules shall initially consist of the substances listed in this section.

The schedules are updated and republished on an annual basis. Oversight for compliance with the law resides with the Drug Enforcement Agency (DEA). Placement on Schedules, Findings Required: are under the purview of the DEA.

Schedule I: The drug or other substance has a high potential for abuse. The drug or other substance has no currently accepted medical use in treatment in the United States. There is a lack or accepted safety for use of the drug or other substance under medical supervision.

Schedule II: The drug or other substance has a high potential for abuse. The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. Abuse of the drug or other substances may lead to severe psychological or physical dependence.

Schedule III: The drug or other substance has a potential for abuse less than the drug or other substance in schedules I and II. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence.

Schedule IV: The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule I-III. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drug or other substance in schedule III.

Schedule V: The drug or other substance has a low potential for abuse relative to the drug or other substance in schedule IV. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drug or other substance in schedule IV.

A written record is required when barbiturates and other drugs that come under the control of the DEA 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 who is authorized to dispense the drug. Within the University of Virginia this authority rests with the principal investigator whose laboratory is using the drug.

An inventory list of anesthetics, analgesics, tranquilizers, sedatives, and other drugs should be kept.

Individual animal records for USDA regulated species (dog, cat, nonhuman primate, hamster, rabbit, guinea pig, etc.) which are anesthetized and allowed to recover should be annotated to reflect the use of the controlled agents described above, showing the date and amount used.

All records should be stored in such a way that they are readily available for review by members of the institutional animal care and use committee or by authorized inspectors from the OPRR, DEA, and USDA.

Drugs such as anti-cholinergics, tranquilizers, or sedatives can be given as pretreatment prior to the administration of anesthetics for a variety of reasons. The primary goal in every case is to diminish to the need for general anesthetics (tranquilizers and sedatives) and prevent bradycardia mediated through the barorecptor reflex and tracheal intubation (anti-cholinergics) or increased parasympathetic activity due to the pharmacology of other drugs which are used.

Anti-cholinergics (i.e. atropine sulfate, glycopyrrolate)

These agents block parasympathetic impulses to the cardiopulmonary system, glands and smooth muscle. Consequently, they prevent vaso-vagal reflexes with concurrent slowing of the heart and they reduce salivary gland and bronchial secretions.

Tranquilizers: (eg. acetylpromazine)

They may be used to calm the animal by reducing fear and apprehension which facilitates restraint without marked sedation. These animals can be readily aroused by painful stimulation because tranquilizers do not produce analgesia.

Reduce the amount of anesthetic required for induction and maintenance of general anesthesia which decreases the undesirable side-effects of the anesthetic agent.

Reduce involuntary reflex responses that may occur unless deep levels of anesthesia are maintained throughout a surgical procedure.

Provide greater skeletal muscle relaxation when the chemical nature of the anesthetic does not produce enough. This effect is seen in rabbits and cats with the administration of a combination of acetylpromazine and ketamine hydrochloride. This activity is not uniformly as strong, however, as the skeletal muscle relaxation that results from the administration of neuromuscular blocking agents like succinylcholine.

Sedatives: (e.g.diazepam)

They may be used to depress the CNS and produce drowsiness which also serves to reduce the amount of anesthetic agent that is needed for induction and maintenance of general anesthesia. There is wide species variation in the reaction to these drugs.

Some sedatives, such as xylazine, also possess analgesic properties.

Non-chemical Pretreatment:

Non-chemical pretreatment procedures such as withholding drinking water and food prior to surgery are advisable to prevent regurgitation of stomach contents and inspiration into the respiratory tract while the animal is anesthetized.

Water can be given ad libitum up to the time of surgery with some species but it should be withheld for several hours particularly ruminates.

Withhold food for: Dogs and cats 8-12 hours; Primates 8-12 hours; Ruminants: 24 hours.

Definition:

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 whereas sedatives at high dose levels cause a profound CNS depression similar to anesthesia.

Functional Use

Used primarily for chemical restraint or as pre-anesthetic medication.

Tranquilizers produce a state of behavioral change in which the animal is relaxed and unconcerned by its surroundings. The animal is often indifferent to minor painful stimuli but will react to higher levels of pain and that reaction may be violent.

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 by the stimulation from painful procedures.

Characteristics:

With the exception of the thiazine derivatives (e.g., xylazine), these compounds have no significant analgesic activity. Increased stimulation by loud noises usually reverses the calming effects of these drugs. When used as pre-anesthetics, ample time should be allowed for the drug to reach its maximum effect before anesthesia is induced. Recovery from general anesthesia is generally smoother when these drugs are used as pretreatments. All tranquilizers and sedatives share the characteristics listed above, but each drug or group of drugs its own diverse pharmacological properties and contraindications.

Classifications of Tranquilizers (ataratics or neuroleptics):

• Phenothiazine derivatives (e.g., acetylpromazine)
• Butyrophenones (e.g. azaperone, droperidol)
• Rauwolfia alkaloids (e.g. reserpine, metoserpate hydrochloride)

 

Classifications of Sedatives (hypnotics):

• Barbiturates (e.g. phenobarbital)
• Benzodiazepines (e.g. diazepam)
• Chloral derivatives (e.g. chloral hydrate)
• Thiazine derivatives (e.g. xylazine, detomidine)

Tranquilizer and Sedative Effects:

Phenothiazines:

Make animals more tractable; cause hypotension secondary to peripheral vasodilation mediated by a-adrenergic blockade; minimally reduce respiratory rate; may lower seizure threshold; cause CNS effects by depressing the brainstem and connections to the cerebral cortex; are metabolized in the liver. NOTE: These agents augment hypothermia through their hypotensive effects so they should be used with caution in small animals or very old animals. These compounds act through dopaminergic receptor blockade and cause blockade of peripheral a-adrenergic receptors leading to profound hypotension.

Acetylpromazine maleate:

Has antiemetic, hypotensive, and hypothermic properties; it is often used in combination with ketamine hydrochloride to increases muscle relaxation; it has been observed to precipitate seizures in gerbils and other individual seizure prone animals.

Chlorpromazine hydrochloride:

Potentiate barbiturate anesthetics; IM injections in rabbits have been associated with severe myositis at the site of injection; produces teratogenic effects in rats and mice.

Butyrophenones (droperidol, azaperone, haloperidol):

Cause animals to act indifferently to their surroundings and decreases their motor activity; cause hypotension, but less than the phenothiazines, and slightly increase the respiratory rate. Effects of the group are similar to the phenothiazines but more potent. Used in combination with narcotics to produce neuroleptanalgesic combinations. These compounds act through dopaminergic receptor blockade and to a lesser extent cause some a-adrenergic blockade.

Rauwolfia Alkaloids (reserpine and metoserpate):

None of these drugs are commonly used in laboratory animal medicine.

Benzodiazepines (diazepam, midazolam):

These drugs cause CNS depression through agonist activity at g-amino butyric acid (GABA) a-type receptors. They have mild cardiovascular depressant effects at low doses; have little effect on respiration. They may have significant species variations in that they cause minimal sedation in most animals but marked in rabbits and rodents. Since they cause minimal cardiopulmonary depression, they are excellent for old animals and those that are metabolically compromised for some other reason. Benzodiazepines bind very well to most plastics; therefore, do not store in plastic syringes. Diazepam (Valium) - Schedule IV drug with anticonvulsant properties; acts on thalamus and hypothalamus with no peripheral blocking actions; metabolizedin liver. Good skeletal muscle relaxation. Diazepam does not mix efficiently with most other drugs in the same syringe but it mixes efficiently with ketamine hydrochloride. Midazolam (Versed) is a water soluble benzodiazepine.

Alpha-2-adrenergic agonists (e.g., xylazine, detomidine):

These drugs produce dose-related CNS depression; cause reflex bradycardia (vagal mediated) via increased sympathetic tone, decreased cardiac output, and increases central venous pressure. They are potent sedatives and hypnotics with excellent analgesic activity. This class of drugs causes cardiovascular and respiratory depression. Bradycardia (slow heart rate) is associated with the reflex increase in parasympathetic tone and 2nd degree heart block may occur. Other electrical cardiac abnormalities have been associated with the overall increase in systemic adrenalin levels due to a2 stimulated adrenergic release from the presynaptic sympathetic in the adrenal glands. This can be prevented by administration of anti-cholinergics. The onset of activity is rapid metabolism in swine. These drugs cross the placental barrier, may cause vomiting due to increased vagal tone, and they alter GI transit time and GI sphincter tone.

Barbiturates (e.g., sodium pentothal):

High doses will produce general anesthesia whereas lower doses cause an excitement stage. This stage can alleviated by the administration of an additional anesthetic.

Sodium pentothal and sodium thiamylal, ultrashort acting barbiturates, can be used at lower doses as a sedative and premedication before anesthesia but the dose must be carefully controlled to avoid the excitement stage.

Chloral derivatives (e.g., chloral hydrate):

Chloral hydrate is a reliable sedative hypnotic but it has poor analgesic properties, even at anesthetic doses. Consequently, it has frequently been used in combination with some other drug such as magnesium sulfate when general anesthesia was the desired endpoint. Intraperitoneal administeration of chloral hydrate to rats is associated with paralytic ileus. a-Chloroalose is a hypnotic frequently used in neuroscience experiments. These drugs have no analgesic activity but can be combined with local or regional anesthesia (novocaine, marcaine, bupivicaine), to produce sufficient traquilization and anesthesia to allow skin incisions and minor surgical procedures.

Reversal of tranquilizing and sedative effects:

No agents are available for most tranquilizers and sedatives. Yohimbine can be used to reverse xylazine. Atipazole can be used to reverse detomidine.

General Anesthetics:

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Definition: Substances that produce, in a controllable manner, loss of consciousness and an absence of motor response to noxious stimuli.

Functional Use: To produce unconsciousness, analgesia, and muscle relaxation sufficient to perform painful procedures painlessly.

General Considerations:

• Administer routine general anesthesia only to healthy animals.
• Use the minimal degree of CNS depression (anesthesia) necessary for performing the procedure, compatible with the animal's welfare (degree of pain associated with the procedure).
•  Consider to what extent the anesthetic protocol will affect the validity of experimental results and how it will interact with other drugs being used. Often two different anesthetic regimens may be necessary to demonstrate the absence of anesthetic influence on the experimental outcome.
•  Even in the absence of sophisticated equipment, try to have some basic items available to insure adequate ventilation for the animal. This includes a method of intubating the animal (endotracheal tube) and method to ventilate the animal (ambu-bag or mechanical respirator). Anesthetic death is most often associated with respiratory depression (mediated centrally in the brain by the drug given) and the hypoxia and hypercarbia which occurs from this. Maintain a patent airway to ensure proper respiration of the animal. This is essential if an anesthetic crisis arises and treatment is administered so that the subject will survive. With small animals that are obligate nose breathers (rats, mice, hamsters, guinea pigs, rabbits), a patent airway is easily maintained if nostrils are not blocked.
•  Monitor and maintain body temperature to avoid hypothermia. Conservation of body heat is an integral part of anesthetic management. Core body temperature can fall precipitously during the course of prolonged general anesthesia, especially in small animals (rodents). Hypothermia added to other factors can produce an irreversible sequence of events leading to death. Hypothermia slows the metabolism of many drugs prolonging anesthesia such that warming the animal at the end of the anesthesia will lead to more rapid and successful recovery. Thermostatically controlled heating pads should always be used during animal surgery.
• In larger species administer warm balanced electrolyte solutions by continuous IV drip throughout the surgical procedure whenever possible to help maintain normal cardiovascular function. A substantial amount of evaporative water loss occurs during procedures which open body cavities and many anesthetics cause some depression of cardiac output and alteration in vascular tone (and hence blood pressure). Intra-peritoneal warmed fluids can be administered to rodents during surgical procedures as a method of maintaining hydration.
•  The anesthetist's responsibility for the welfare of the animal extends beyond the end of the surgical procedure to the time that the animal is able to maintain itself in sternal recumbency and breathing normally.
• Consider the safety of personnel who will be in the area during the use of an anesthetic gases and provide a gas scavenging system if volatile anesthetics are used (halothane, metofane, enflurane, isoflurane).

 Dosage principles for general anesthesia:

 Evaluate the physical condition of the animal to assure that there is no disease condition that may compromise the health of the animal during anesthesia.

Calculate dose by "lean" body weight and age.

Administer drugs to effect. Because of the wide variation within and among species, there is really no such thing as a predetermined anesthetic dose of a drug. General anesthesia must be given "to effect," as measured by physiologic parameters and response to external stimuli. It is important to realize that some drugs take time to take effect. Most anesthetic deaths can be attributed to not giving the anesthetic time to work. This is especially true of parenteral administered drugs (e.g., barbiturates) - once they are injected, there is little the anesthetist can do to control the outcome.

Allow for variations in response to agent between species and between individuals of the same species because the absorption and bio-transformation processes can be very different.

Pre-treat with tranquilizers or sedatives to decrease the amount of anesthetic needed to prevent pain and distress.

Stages of general anesthesia

Stage I

• Stage of analgesia or voluntary movement.
• Duration: From onset of administration to loss of consciousness.

Stage II

• Stage of delirium or involuntary movement.
• Duration: From loss of consciousness to onset of regular pattern of breathing.

Stage III

• Stage of surgical anesthesia.
• Characterized by unconsciousness, with progressive depression of reflexes; muscular relaxation; slow, regular respiration; and loss of vomiting and swallowing reflexes.
• Divided into planes I through 4, where plane I is light anesthesia, planes 2 and 3 are medium anesthesia, and plane 4 is deep anesthesia.

Stage IV

• Characterized by extreme CNS depression. Death ensues quickly unless resuscitative steps are taken.
• Evaluation of general anesthetic effects

Ocular reflexes are quite variable and should not be used as the sole criteria for the evaluation of the adequacy of anesthesia. In general, palpebral reflex associated with touching the eyelids is lost in light to medium planes of surgical anesthesia. Corneal reflexes are very inconsistent between species and should only be used with care. The corneal reflex is lost in the rabbit at very deep planes of surgical anesthesia. The palpebral reflex is blocked by ketamine anesthesia.

Test reflexes such as the pedal and palpebral reflexes, and the tone of jaw and anal sphincter muscles (reflexes are absent and muscle tone is relaxed during anesthesia). Rabbits, hamsters and guinea pigs may demonstrate spontaneous movements at all stages and planes of anesthesia. Surgical anesthesia in these species is normally accompanied by the disappearance of head shaking in response to pinching of the ear. The pattern of respiration, slow regular deep breaths, has been demonstrated to be a better sign of the level of surgical anesthesia in rabbits. Ketamine causes an abnormal respiratory pattern termed apneustic which is characterized by short inspirations and prolonged expirations.

 Monitor depth and rate of respiration (increase in depth and decrease in rate signifies anesthesia). Guinea pigs and rabbits may hold their breath when excited or when exposed to certain inhalation agents. Surgical anesthesia is accompanied by breathing at a slower and more regular rate. Violent alterations secondary to surgical stimulation may indicate inadequate anesthesia. If the animal is to deep the inspiratory effort is often labored and coupled with pronounced movement of the abdominal muscles without movement of the thoracic muscles. Because the airways of many laboratory animals are easy to obstruct, the animals neck should be extended during surgical manipulation.

Monitor heart rate (slowing indicates 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.

Monitor body temperature (temperature falls in anesthesia; warming causes faster metabolism of anesthetic) Maintain temperature at normal levels.

Indications of anesthetic overdose:

• Heart rate may be rapid or slow depending on the animal's state of physiological decompensation. A slow heart rate when blood pressure is low is an example of decompensation, a rapid heart rate which diminished pulse pressure is another example.
• Pulse may be weak to imperceptible.
• Blood pressure is reduced to shock level.
• Cardiac dysrhythmias may occur.
• Capillary refill time (the time for blood to flow into a vascular bed, gums, beneath the nails, after being blanched by digital pressure) progressively slows to 3 or more seconds.
• Respiration is slow, irregular, and becomes diaphragmatic (no rib component) or may cease.
• Mucous membrane and skin colors are pale to cyanotic. 
• Gastrointestinal, ocular, musculo-skeletal, and nervous system reflexes are greatly diminished or absent.

Intervention for anesthetic overdose:

• Mechanically ventilate with oxygen or at a minimum room air. At times respiration can be stimulated digitally by applying mild pressure to the chest wall. If total respiratory collapse is observed a tight fitting face mask or rubber tube, placed over the animals mouth and nose, can be used to ventilate the animal. Care must be utilized to maintain filling pressures at 10-15 cm H2O. Pressures reaching or exceeding 25-30 cm H20 will begin to rupture alveolar walls.
• Administer isotonic fluids intravenously or intra-peritoneally.
• Warm animal to increase body temperature.
• Administer reversal agent, if one exists, or a respiratory stimulant (Doxapram, bemegride).

General Anesthetic Agents:

Injectable (Barbiturates):

Once these agents are administered their effects cannot be reversed because the drug must be metabolized or counteracted upon by the action of another drug before the anesthetic action is terminated.

The use of many injectable anesthetic agents as controlled substances, i.e. barbiturates, must be documented in compliance with the Controlled Substances Act.

Many of these agents, will produce sedation associated with severe respiratory depression and general anesthesia as larger doses are administered. At high doses these agents are utilized for euthanasia.

Prolonged recovery from barbiturate anesthesia is associated with glucose, epinephrine, chloramphenicol, and hypothermia. Softwood beddings which induce hepatic microsomal enzymes in rodents, decrease barbiturate sleeping time.

Some barbiturates are caustic substances when injected into living tissue and so must be give intravenous or diluted and given intraperitoneal. Avoid subcutaneous or intra-muscular injections with these drugs. Intra-peritoneal injections are acceptable only with pentobarbital sodium (Nembutal).

All barbiturates are poor analgesics unless administered to unconsciousness.

Examples:

Pentobarbital sodium (Nembutal) - long acting; small safety margin, intravenous or intraperitoneal injection.

Thiamylal sodium (Surital) or sodium pentothal - short acting (15 to 30 minutes). Intravenous or intraperitoneal injection only. Avoid repeated doses due to cumulative effects. Calculate dose on lean body weight only.

Inhalation Agents

The duration of effect of these agents can be terminated quickly because expiration of the anesthetic gas begins immediately upon termination of the administration of the agent. Inhalant anesthetics have a rapid onset and high degree of controllability.

The reversal process can be hastened significantly by the administration of oxygen after the anesthetic gas is stopped. Oxygen therapy is recommended after inhalation anesthesia as the anesthetic agent floods lung alveolar spaces when the source is removed and may cause transient dilutional hypoxia in the immediate post-anesthetic period.

Examples:

Halothane (Fluothane) - highly volatile but relatively insoluble (halothane saturated atmosphere can reach a 30% concentration); requires the use of a precision vaporizer for precise concentrations; potent cardiovascular depressant which gives fair muscle relaxation and analgesia; nonexplosive.

Methoxyflurane (Metofane) - poorly volatile reaching a free gas concentration of approximately 4% in air, highly fat soluble; muscle relaxation and analgesia good; respiratory depressant; enhances myocardial contractility; nonexplosive; inhalation anesthetic of choice for rodents. Has a prolonged onset in larger species and prolonged recovery.

Isoflurane - Isomer of enflurane. Maintains cardiac output better than other volatile agents. Respiratory depression. Rapid recovery may cause possible emergence delirium. Less bio-transformation than other inhalation agents. Pungent smell may cause breath-holding during mask or chamber induction. Good muscle relaxation and analgesia.

Nitrous oxide - potent analgesic; useful in conjunction with halothane and methoxyflurane; nonirritating; very insoluble in blood and tissues resulting in rapid induction and recovery; nonexplosive.

Diethyl ether - highly volatile and soluble; provides good analgesia and muscle relaxation; vapors irritate respiratory mucosa; VERY DANGEROUS as is flammable and explosive; not approved for use as an anesthetic agent at the University of Virginia.

Dissociative Agents (Ketamine, Tiletamine (Telazol, Sernylan):

Dissociative anesthetics produce a state of chemical restraint and anesthesia characterized by a form of muscle rigidity and an apparent dissociation of the mind from the external environment (catalepsy); agents do not depress the central nervous system; reflexes remain intact; tracheal intubation possible; produce excessive salivation that is controllable with atropine. These agents cause blockade of N-methyl D aspartate (NMDA) receptors and has been demonstrated to be neuroprotective for some neurons during ischemia.

These agents are do not have strong analgesic properties so their use must be limited to minor surgery or other procedures that are not likely to cause deep levels of pain. They can also be used in conjunction with other agents to provide greater analgesia.

Larger doses may produce convulsions.

Many adverse effects can be minimized by the addition of tranquilizers, like the benzodiazepines.

• Ketamine hydrochloride (Vetalar or Ketaset) - preferred dissociative anesthetic due to a wide margin of safety; short duration and recovery time with few adverse side effects; it produces poor musclar relaxation which is often relieved by concurrent administration of benzodiazepines Ketamine is contraindicated for use in animal with renal or hepatic disease.

 Definition:

Substances that temporarily alleviate pain without loss of consciousness.

 Functional Uses:

• Control pain without the use of anesthetics.
• As a preanesthetic, it may reduce the amount of anesthetic that is required.
• Relieve postoperative pain.

 Narcotics (Opiates and Opioids):

 Narcotic agents and narcotic antagonists all must be handled in adherence to the Controlled Substances Act.

•  Narcotics produce their major effects on the central nervous system (CNS) and gastrointestinal system. These agents produce hypnotic and analgesic effects with resultant depression of the cardiovascular and thermoregulatory systems; attach to opiate sites in the CNS and block neurotransmitters, elevating the pain threshold. Opiates are associated with systemic histamine release from mast cells.
•  Effects of narcotics include analgesia, respiratory depression, decreased gastrointestinal motility, nausea, vomiting (mediated centrally), and alterations of the endocrine and autonomic nervous systems.
•  Narcotics decrease the amount of other agents needed for general anesthesia by 1/3 to 1/2; most are metabolized by the liver and excreted in the bile and urine.

 Actions and doses vary significantly among species. The actions of some analgesics have not been determined for some of laboratory animals.

 Morphine -

• used primarily in dogs and primates, and can cause excitement in cats, increased motor activity in horses and food animals; duration of action of 4-6 hours; stimulates vomiting and vagal CNS centers; causes increased intraocular and intracranial pressure; relatively inexpensive.

Meperidine (Demerol) -

• 1/10 as potent as morphine; preferred over morphine because of fewer side effects; used in dogs, cats, rodents, and primates; duration of action of 2-3 hours.

Fentanyl -

• potent, short acting, reversible narcotic used in Innovar-Vet; 100 times more potent than morphine; effects last 30-60 minutes.

 Sufentanil (Sufental) -

• 200 to 250 times more potent than morphine.

 Etorphine hydrochloride (M99) -

• synthetic derivative of the opium alkaloids; approximately 1000 times more potent than morphine; used for reversible immobilization of zoo animals and wild game.

 Mixed agonsts/antagonist cause blockade of some opiate receptor subtypes while stimulating others (nalbuphine, buprenorphine). These drugs can provide analgesia without euphoria (so are schedule IV) and produce minimal respiratory depression.

 Narcotic antagonists (e.g., naloxone, nalorphine) can prevent or promptly reverse the analgesic, gastrointestinal, depressant, and convulsant effects of opioids by displacing another compound at the receptor site; will not reverse the sedative or depressant effects of other drugs. Narcotic antagonists are Schedule III drugs.

 Non-narcotic analgesics:

 Xylazine (Rompun) and Medetomidine-

• are thiazine derivatives which causes sedation, muscle relaxation, and analgesia; wide margin of safety; may cause emesis via direct central stimulation or by indirect increase in parasympathetic activity; potentiates barbiturate anesthesia; may precipitate early parturition if given to animals in last month of pregnancy; yohimbine partially reverses the effects of xylazine.

 Non-steroidal antiinflammatory Drugs (NSAIDs) -

• analgesic, antipyretic, and anti-inflammatory effects; aspirin (salicylate) is the best known; most effective for the relief of muscular pain and has minimal effect for the relief of visceral pain. This class of compounds includes acetominophen, ibuprofen, carprofen, naprosin, etc.

Pentazocine (Talwin) -

• 1/2 as potent as morphine; duration of action of action averages 2 hours; produces little or no sedation; minimal effect on the cardiovascular and respiratory systems.

 Neuroleptanalgesics:

• Neuroleptanalgesics produce a state of sedation and analgesia produced by the combination of a tranquilizer (neuroleptic) and narcotic. The animal remains conscious and responds to certain stimuli.
• States of deep sedation and analgesia adequate for surgical intervention have been produced in dogs, rats, and nonhuman primates.
• A peculiar characteristic of this state in dogs and rats, but not nonhuman primates, is the capacity to respond to auditory stimuli (e.g., dropping an object, crumpling paper).
• Pedal reflex is absent.
• Maximum analgesia persists for 30-40 minutes, after which there may be a reaction to cutaneous stimulation even though generalized sedation and some analgesia are still evident.

 Innovar-Vet -

• narcotic analgesic fentanyl (0.4 mg/ml) plus tranquilizer droperidol (20 mg/ml); good analgesia and muscle relaxation; produces mild, atropine sensitive bradycardia; narcotic antagonists can reverse the effects of the fentanyl only.

Definition: 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 drugs can cause direct cholinergic polarization of electrically excitable membranes (succinyl choline) or be non-depolarizing (pancuronium)

Functional Use: Adjuvant in surgical anesthesia to obtain complete musclar relaxation for procedures such as bone fracture repair in heavily muscled animals or thoracic procedures to prevent respiratory excursions except during intentional ventilation of the patient.

Effects:

Depolarizing neuromuscular blocking drugs (e.g., succinylcholine) interact with and depolarize the receptor areas, causing a lack of responsiveness to acetylcholine. These agents can not be reversed.

Competitive neuromuscular blocking agents (e.g., d-tubocurarine, pancuronium) combine with the receptors and render them inaccessible to acetylcholine. The action of these agents can be reversed by using cholinesterase inhibitors (2-PAM).

These agents produce muscle paralysis only, and do not produce either sedation or analgesia. These agents should never be used as anesthetic or analgesic agents (9 CFR 2.3 1; NRC, 1985; PHS, 1986).

Classification:

• Depolarizing agents - decamethonium (Syncurine) and succinylcholine (Anectine).
• Nondepolarizing agents - tubocurarine USP, gallamine (Flaxadil), and pancuronium (Pavulon).

Monitoring of Anesthesia During the Use of Neuromuscular Blocking Agents

• Many signs of anesthesia are abrogated during the use of a neuromuscular blockade. The animal's inability to respond to stimuli are paralyzed so that many methods used to judge the depth of anesthesia become impaired or precluded. The following should be used as guidelines in monitoring the depth of anesthesia of a paralyzed surgical patient.
• The principal source of distress in paralyzed patients is respiratory, therefore careful monitoring of oxygenation and carbon dioxide levels is necessary. This can be done in the form of blood gas analysis or oximetry/capnography. Regular direct monitoring is required.
• Heart rate must be monitored for increases during the performance of noxious/distressing procedures. An increase may indicate conscious perception of pain in the paralyzed patient. Monitoring of blood pressure is also recommended as increases in blood pressure may similarly be associated with perception of noxious stimuli.
• Body temperature should be monitored and maintained within normal limits. Immobilization prevents the shivering response

The following pages provide tables of drugs commonly used for pre-anesthesia, anesthesia, analgesia, sedation, tranquilization, and restraint of laboratory animal species. Some physiological data and comments are added as well.

Mouse	Rat	Cat
Dog	Rabbit	Hamster
Guinea pig	Sheep and Goat	Swine
	Nonhuman Primates	Amphibians

The dosage recommendations and other data presented on the following pages are based upon current data in the literature and the professional judgement of veterinarians at the University of Virginia. Doses published in the literature are often variable.

Proper drug doses may vary greatly depending on species, strain, sex, age, physiologic status of the animal, and the level of anesthesia/analgesia desired.

Although these lists provide a ready source of information on drug doses, individuals should not use these drugs without prior experience.

Your institute or animal facility veterinarians are available for consultation and additional information.

Controlled drugs are identified by a "C." The Roman numeral classifies the drug into one of the five established schedules of controlled substances (e.g., sodium pentobarbital, C-II).

  MOUSE (Mus musculus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04 mg/kg	IM
Diazepam, C-IV (Valium)		0.5 mg/100 g	IP
Ketamine(10 mg/ml)		2.2-4.4 mg/100 g	IM
Ketamine/Acetylpromazine(10:1)		2.2-4.4 mg/100 g dosage based on Ketamine	IM
Sodium Pentobarbital,C-II		3-4 mg/100 g	IP
Carbon dioxide		To effect	IH

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		5-9 mg/100 g	IP
Ketamine (Ketaset or Vetalar)		5-20 mg/100 g	IP
Ketamine (Ketaset or Vetalar)		4-6 mg/100 g	IM
Avertin (Tribromoethanol) 2.5%		0.015-0.017 ml/g	IP
Ketamine/Xylazine: - Add 7 mg xylazine to 35 mg ketamine (dose based on ketamine)		7-8 mg/100 g	IM IP
Ketamine/Xylazine: - Add 1.0 ml xylazine (20 mg/ml) and 2.0 ml ketamine (100 mg/ml) and 7.0 ml sterile water.		0.1-0.15 ml/20-25 g	IM IP
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Carbon dioxide		To effect	IH
Telazol		10-16 mg/100 g	IP IM
Propofol		1 0 mg/kg	IV (short-acting; cont. IV possible)

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		0.5-1.0 mg/100 g q2-4h	SC IP
Meperidine, C-II (Demerol)		0.2-0.4 mg/100 g	IP
Pentazocine, C-IV (Talwin)		0.3-1.0 mg/100 g q3-4h	IM
Butorphanol tartrate (Torbugesic)		0.25-0.5 mg/100 g ql-2h	SC
Buprenorphine (Buprenex)		0.2 mg/kg ql2h	SC IP

Selected Physiological Parameters

Body temp - 36.5 - 38oC	Heart rate - 325 - 780 bpm
Respiratory rate - 60 - 220 bpm	Tidal volume - 0.1 ml/20 gm

* Mice actively renal excrete creatinine and taurine unlike other mammalian species.

Dog (Canis familaris)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04 mg/kg	IM SC IV
Acetylpromazine		0.055-0.11 mg/kg 0.55 -2.2 mg/kg	IM SC IV PO
Xylazine (Rompun)		1.1-2.2 mg/kg 1.1 mg.kg	IM SC IV
Diazepam, C-IV (Valium)		1-5 mg/kg	IV

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II x(3% solution given slowy to effect)		30 mg/kg	IV
Ketamine/Xylazine xxxxXXXKetamine XXxxxxx Xylazine		10 mg/kg 1 mg/kg	IM IM
Ketamine/Diazepam (2:1) xxxxxxxxxKetamine xxxxxxxxxDiazepam		5.0 mg/kg 0.3 mg/kg	IV IV
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Halothane/Nitrous Oxide (50% O2/50% N2O)		To effect	IH
Propofol		3-4 ml/kg/hr	IV

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		0.5-5 mg/kg q2-4h	SC
Acetylsalicylic Acid (Aspirin)		25 mg/kg q8h	PO
Phenylbutazone		22 mg/kg q8h	PO
Flunixin meglumine (Banamine)		1.1 mg/kg daily	IV
Butorphanol tartrate (Torbugesic)		0.055-0.11mg/kg q6-12h	SC
Butorphanol tartrate (Torbugesic)		0.55 mg/kg q6-12h	PO
Buprenorphine (Buprenex)		0.01-0.02 mg/kg q12h	SC IM

Reversal Agents

Drug		Dosage	Route of Administration
Yohimbine		0.1 mg/kg	IV
Naloxone (Narcan)		0.02-0.04 mg/kg	IV IM

Selected Physiological Parameters

Body temperature = 39oC	Heart rate =100-130/min
Respiratory rate = 22/min	Tidal volume = 7-10 ml/kg

1. Ketamine should not be used alone in dogs as it may cause seizures in some individuals.
2. Ketamine should be used in combination with a tranquilizer.

GUINEA PIG (Cavia porcellus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.05 mg/kg	SC
Diazepam, C-IV (Valium)		2.5-5.0 mg/kg	IP IM
Acetylpromazine		5-10 mg/kg	IM SC IV
Meperidine, C-II (Demerol)		1-2 mg/kg	IM IP
Ketamine		22-30 mg/kg	IM IP

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		15-40 mg/kg	IP
Sodium Thiopental, C-III		20 mg/kg	IV
Ketamine (Ketaset, Vetalar)		40-50 mg/kg	IM
Ketamine/Acetylpromazine (10:1) XXXXX(dose based on Ketamine)		40-50 mg/kg	IM
Ketamine/Xylazine xxxxKetamine XX Xylazine		44 mg/kg 5 mg/kg	IM IM
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		1 mg/100 g q2-4h	SC IM
Meperidine, C-II (Demerol)		2 mg/kg	IM SC
Pentazocine, C-IV (Talwin)		2-10 mg/kg	IM SC
Buprenorphine (Buprenex)		0.005 mg/100 g q8-12h	SC

Selected Physiological Parameters

Body temperature = 37.2-39.5oC	Heart rate = 230-380/min
Respiratory rate = 42-104/min	Tidal volume = 2.3-5.3 ml/kg

1. Large cecum can act as reservoir for anesthetics. Depending on drug solubility, the cecum can alter the pharmacologic effect.
2. Induction of anesthesia using volatile anesthetics (e.g., halothane and isoflurane) should be done with caution due to initial breath holding when animals are first exposed to irritating gas vapors.
3. Repeated exposure to halothane can cause hepatotoxicity. Methoxyflurane and isoflurane are safer inhalant anesthetics to use.
4. Inovar-Vet given IM can cause severe tissue necrosis in guinea pigs. Contraindicated for IM use in guinea pigs due -to severe necrotic myositis at injection site. Self mutilation may occur after recovery.
5. Self mutilation has been reported in guinea pigs after ketamine administration.

    

  RAT (Rattus norvegicus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04-0.1 mg/kg	SC
Diazepam, C-IV (Valium)		0.05-1.5 mg/100 g	IP
Ketamine(Ketaset, Velar)		2.5-5.0 mg/100 g	IM
Ketamine/Acetylpromazine(10:1)dosage based on Ketamine		2.5-5.0 mg/100 g	IM
Carbon dioxide		To effect	IH

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		2-4 mg/100 g	IV IP
Ketamine (10 mg/ml solution)		5-9 mg/100 g	IM IP
Ketamine/Xylazine xxxxKetamine XX Xylazine		8 mg/100 g 0.8 mg/100 g	IM IP IM IP
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Carbon dioxide		To effect	IH
Telazol		2-4 mg/ 100g	IP
Telazol		2 mg/ 100g	IM
Ketamine: Medetomidine Medetomidine reversable with atipamezole (1mg/kg SC)		75mg/kg + 1.0mg/kg	IP

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		0.15-0.6 mg/100 g q2-4h	SC
Meperidine, C-II (Demerol)		0.2 mg/100 g	IM
Pentazocine, C-IV (Talwin)		0.2-1.0 mg/100 g q4h	IM
Butorphanol tartrate (Torbugesic)		0.25-0.5 mg/100 g ql-2h	SC
Buprenorphine (Buprenex)		0.01-0.05 mg/100 g ql2h	SC

Reversal Agents

Drug		Dosage	Route of Administration
Yohimbine		1 -2 mg/kg	IM IP

Selected Physiological Parameters

Body temp - 35.9 - 37.5oC	Heart rate - 240 - 450 bpm
Respiratory rate - 70 - 115/bpm	Tidal volume - 0.5 ml/100 gm

1. Methoxyflurane use contraindicated for F344 rats as it produces a diabetes insipidus-like syndrome in this strain.
2. Male rats and animals receiving low calorie diets require higher doses of barbiturates.
3. Avertin and chloral hydrate cause paralytic ileus in rats
4. The therapeutic dose for carbon dioxide is close to the lethal dose; very short acting.

RABBIT (Oryctolagus cuniculus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Ketamine		15-50 mg/kg	IM
Acetylpromazine		1.0-10 mg/kg	IM
Ketamine/Acetylpromazine(10:1)		15-50 mg/kg	IM
Diazepam, C-IV (Valium)		5-10 mg/kg	IV IM
Glycopyrrolate		0.005-0.011 mg/kg	IM

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II x(3% solution given slowy to effect)		15-40 mg/kg	IV
Ketamine (Ketaset, Vetalar)		22-50 mg/kg	IM
Ketamine/Acetylpromazine(add 1cc Ace to a 10cc bottle of Ketamine) xxxxxxxAcetylpromazine xxxxxxxKetamine(dose given based XXXXXXXXXXon Ketamine)		5.0 mg/kg 50 mg/kg	IM IM
Ketamine/Xylazine xxxxKetamine XX Xylazine		40-60 mg/kg 5 mg/kg	IM IM
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		5 mg/kg q2-4h	SC
Meperidine, C-II (Demerol)		2-10 mg/kg	IM IV
Pentazocine, C-IV (Talwin)		10-20 mg/kg q4h	IM
Acetylsalicylic Acid (Aspirin)		500 mg/kg	PO
Buprenorphine (Buprenex)		0.02-0.1 mg/kg q8-12h	SC

Reversal Agents

Drug		Dosage	Route of Administration
Yohimbine		0.2 mg/kg	IV

Selected Physiological Parameters

Body temperature = 38-39.6oC	Heart rate = 130-325/min
Respiratory rate = 32-60/min	Tidal volume = 4-6 ml/kg

1. Many rabbits have serum cholinesterase which causes reduced response to atropine. Glycopyrrolate, another anti-cholinergic, can be used instead of atropine.
2. Unique hypnotism or immobilization reflex has been observed in rabbits in the absence of drug use.
3. Large cecum can act as reservoir for anesthetics. Depending on drug solubility, the cecum can alter the pharmacological effect.
4. Induction of anesthesia using volatile anesthetics (e.g., halothane and isoflurane) should be done with caution due to initial breath holding when animals are first exposed to irritating gas vapors.
5. Give IV injections via marginal ear veins.

 

SHEEP (Ovis aries) and GOAT (Capra hircus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine xxxxxxx repeat every 15-30 minutes		0.1-1.0 mg/kg 0.2 mg/kg	IM SC IV IV
Ketamine		2-7 mg/kg	IV
Acetylpromazine		0.05-1.0 mg/kg	IM SC IV
Diazepam, C-IV (Valium)		0.2-0.5 mg/kg	IV IM

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		30-40 mg/kg	IV
Sodium Thiopental, C-III (5%)		22 mg/kg	IV
Ketamine/Xylazine xxxxXXXKetamine Xx Xylazine(w/ atropine,wait 10min)		11-22mg/kg 0.2 mg/kg	IV IM
Halothane (Fluothane)		To effect	IH
Halothane/Nitrous Oxide (50% O2/50% N2O)		To effect	IH

Analgesia

Drug		Dosage	Route of Administration
Meperidine, C-II (Demerol)		3 mg/kg	IM
Phenylbutazone		4-8 mg/kg q24h 2-5 mg/kg q24h	PO IV
Xylazine (Rompun)		0.05 mg/kg	IV
Butorphanol tartrate (Torbugesic)		0.3 mg/kg	SC IV
Acetylsalicylic Acid (Aspirin)		10 mg/kg q4h	PO
Buprenorphine (Buprenex)		0.005 mg/kg q12h	SC

Reversal Agents

Drug		Dosage	Route of Administration
Yohimbine		0.2 mg/kg (ovine)	IV

Selected Physiological Parameters

Body temperature = 39.5oC	Heart rate =60-120/min (sheep) Heart rate=70-135/min (goat)
Respiratory rate = 20/min	Tidal volume = 7-8 ml/kg

1. Xylazine should be used in the 20 mg/ml concentration (small animals); allows better dosage control.
2. Anesthetic combination: Mix 1 ml xylazine (100 mg/ml), 1 ml butorphanol tartrate (Torbugesic), and 8 ml sterile water. Dose this combination at .05 mg/kg IV followed by 1 ml ketamine IM.
3. Aspirin should be used cautiously and not for extended periods to prevent gastric ulcer formation.
4. Sheep and goats should be fasted for 18-24 hours prior to induction of anesthesia to control regurgitation. Water should be withheld for about 6 hours.
5. Positioning of ruminants during anesthesia is an important consideration. Right lateral recumbency should be avoided, as this results in intra-abdominal pressure, pressure on the diaphragm, and the collection of gas in the rumen.
6. Saliva may continue to flow in considerable quantities during general anesthesia in ruminants.

CAT (Felis catus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04 mg/kg	IM SC IV
Ketamine		11mg/kg	IM
Ketamine/Acetylpromazine(10:1)dosage based on Ketamine		11mg/kg	IM
Acetylpromazine		0.055-0.11 mg/kg	IM SC
Xylazine (Rompun)		1.1-2.2 mg/kg 1.1 mg.kg	IM SC IV
Diazepam, C-IV (Valium)		1 mg/kg	IV

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		30 mg/kg	IV
Sodium Thiopental, C-III (2.5%)		15-25 mg/kg	IV
Ketamine (Ketaset, Vetalar)		22-33 mg/kg	IM
Ketamine/Acetylpromazine(10:1)dosage based on Ketamine		22-33 mg/kg	IM
Ketamine/Xylazine xxxxXXXKetamine XXxxxxx Xylazine		10 mg/kg 1 mg/kg	IM IM
Ketamine/Diazepam (2:1) xxxxxxxxxKetamine xxxxxxxxxDiazepam		5.0 mg/kg 0.3 mg/kg	IV IV
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Telazol		2-3 mg/kg	IM

Analgesia

Drug		Dosage	Route of Administration
Meperidine, C-II (Demerol)		3 mg/kg	IM
Xylazine (Rompun)		2 mg/kg	IM SC
Butorphanol tartrate (Torbugesic)		0.3 mg/kg	SC IV
Buprenorphine (Buprenex)		0.005-0.01 mg/kg q12h	SC

Reversal Agents

Drug		Dosage	Route of Administration
Yohimbine		0.1 mg/kg	IV
Naloxone (Narcan)		0.02-0.04 mg/kg	IV IM

Selected Physiological Parameters

Body temperature = 39.5oC	Heart rate =110-140/min
Respiratory rate = 26/min	Tidal volume = 7-10 ml/kg

Nonsteroidal anti-inflammatory drugs should generally not be used in cats. Acetaminophen, ibuprofen, flunixin meglumine, and phenylbutazone are contraindicated. Aspirin is toxic to cats and must be dosed very carefully. Aspirin can cause bone marrow depression, anemia, gastric lesions, and death.

HAMSTER (Mesocricetus auratus)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.01 m /100g	IP IM SC
Ketamine (10mg/ml)		2.2-4.4 mg/100 g	IM
Ketamine/Acetylpromazine (10:1) XXXXX(dose based on Ketamine)		2.2-4.4 mg/100 g	IM
Chlorpromazine		0.05 mg/100 g	IM

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		3-9 mg/100 g	IP
Ketamine or Ketamine/Acetylpromazine: 10:1 dose based on Ketamine		4-15 mg/100 g 10-20 mg/100 g	IM IP
Ketamine/Xylazine xxxxKetamine XX Xylazine		0.3-0.5 mg/100 g 4-6 mg/100 g	IM IP IM IP
Halothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Carbon dioxide		To effect	IH
Telazol		2-8 mg/ 100g	IP IM

Analgesia

Drug		Dosage	Route of Administration
Meperidine, C-II (Demerol)		0.2 mg/100 g	IM
Buprenorphine (Buprenex)		0.05-0.1mg/kg Q12H	SC
Pentazocine, C-IV (Talwin)		0.2-0.3 mg/100 g	IM

Selected Physiological Parameters

Body temperature = 37-38oC	Heart rate = 250-500/min
Respiratory rate = 35-135/min	Tidal volume = 0.5 ml/50 gm

1. Syrian or golden hamsters are very resistant to morphine - no sedative or hypnotic effects.
2. Syrian or golden hamster has an increased tolerance to pentobarbital

    

SWINE (Sus scrofa)

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04mg/kg	IM
Sodium Pentobarbital, C-II		8-11 mg/kg	IV
Acetylpromazine		0.11-0.22 mg/kg	IM
Xylazine (Rompun)		2 mg/kg	IV
Diazepam, C-IV (Valium)		0.55-8.5 mg/kg	IV

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		15-35 mg/kg	IV IP
Sodium Thiopental, C-III (5%)		5-10 mg/kg	IV
Ketamine (Ketaset, Vetalar)		15-20 mg/kg	IM
Ketamine/Xylazine xxxxXXXKetamine Xx xxxxx Xylazine		20 mg/kg 2 mg/kg	IM IV
Acetylpromazine/Ketamine xxxxXXXAcetylpromazine Xx xxxxx Ketamine		0.44 mg/kg 22 mg/kg	IM IM
Xylazine/Telazol xxxxXXXXylazine Xx xxxxx Telazol		2 mg/kg 6 mg/kg	IM IM
Halothane (Fluothane)		To effect	IH
Halothane/Nitrous Oxide (50% O2/50% N2O)		To effect	IH

Analgesia

Drug		Dosage	Route of Administration
Phenylbutazone		4-8 mg/kg q24h	PO
Acetylsalicylic Acid (Aspirin)		10-20 mg/kg q8h	PO
Morphine, C-II		0.2-0.9 mg/kg	IM
Meperidine, C-II (Demerol)		4 mg/kg	IM
Buprenorphine (Buprenex)		0.005-0.01mg/kg q8-12h	IM

Selected Physiological Parameters

Body temperature = 39oC	Heart rate =58-86/min
Respiratory rate =10-20/min	Tidal volume = 11 ml/kg

AMPHIBIANS

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Anesthesia

Amphibians must be kept moist over their entire bodies during anesthesia and recovery. Care must be taken that they do not become immersed, as this will result in drowning.

Tricaine (MS 222)-	ethyl M-amino benzoate methanesulfonate (tricaine methane sulfonate) immerse in water with agent added: 1:2000 to 1:1000 for adults (i.e., 0.5-1 ml of tricaine in 1000 ml water) 1:3000-5000 for larvae induction in 5-20 minutes; maintain by moist cloth contact with MS 222 solution. recovery- keep at 22-260C; takes 3-6 hours; keep moist
Halothane/Isoflurane-	5% in anesthetic chamber; maintain at 3%
Sodium Pentobarbital-	60 mg/kg; inject into dorsal lymph sac.

NONHUMAN PRIMATES

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Restraint/Pre-anesthetic

Drug		Dosage	Route of Administration
Atropine		0.04mg/kg	IM SC
Acetylpromazine		0.5-1.0 mg/kg	IM SC
Ketamine		see Ketamine for NHP
Diazepam, C-IV (Valium)		0.5 - 1.0 mg/kg	IM IV

Anesthesia

Drug		Dosage	Route of Administration
Sodium Pentobarbital, C-II		20-25 mg/kg	IV
Sodium Thiopental, C-III (2.5%)		25 mg/kg	IV
Ketamine (Ketaset, Vetalar)		see Ketamine for NHP
Ketamine/Xylazine xxxxXXXKetamine Xx xxxxx Xylazine		10-20 mg/kg 0.5 mg/kg	IM IM
Ketamine/Diazepam: xxxxXXXKetamine Xx xxxxxDiazepam		10-20 mg/kg 0.5 mg/kg	IM IM
Telazol		2-6 mg/kg	IM
Xx xxxxxHalothane (Fluothane)		To effect	IH
Isoflurane		To effect	IH
Halothane/Nitrous Oxide (50% O2/50% N2O)		To effect	IH

Analgesia

Drug		Dosage	Route of Administration
Morphine, C-II		0.5-2.0 mg/kg q4h	SC IM IV
Oxymorphone, C-II xxxxxxxxOld World Primates xxxxxxxxNew World Primates		0.15 mg/kg 0.075 mg/kg	SC IM IV SC IM IV
Meperidine, C-II (Demerol)		2-4 mg/kg	IM
Pentazocine, C-IV (Talwin) xxxnot to exceed total dose of 60mg		1.5-3 mg/kg q3-4h	IM SC
Buprenorphine (Buprenex)		0.01-0.03mg/kg q6-12h	IM
Acetylsalicytic Acid (Aspirin )		10-20 mg/kg q6h	PO
Acetaminophen		10 mg/kg q8h	PO
Butorphanol tartrate (Torbugesic)		0.025 mg/kg q3-6h	IM

Selected Phy