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THE INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC)

ANESTHESIA AND ANALGESIA IN LABORATORY ANIMALS AT UCSF

I. Overview
II. Species-specific considerations
III. Commonly used anesthetics and analgesics
IV. Species-specific anesthesia-analgesia formularies:

Cat
Dog
• Frog
• Fish

• Guinea Pig
• Hamster
Mouse
Nonhuman primates

Rabbit
Rat
Swine

II. SPECIES-SPECIFIC CONSIDERATIONS

In general, smaller animals have higher metabolic rates and frequently require higher doses at more frequent intervals to achieve the desired effect. Species, strain and age differences often overshadow this general principle however. It is always best to start with a drug regimen developed in the species, age and strain with which the Principal Investigator is working, rather than extrapolate from one species to another.

Mice

Isoflurane is encouraged as the first choice anesthetic in mice. It should be delivered as a known percentage (1-3% for maintenance; up to 5% for induction) in oxygen from a precision vaporizer. See: Inhalant Anesthetics

Anesthetic monitoring of small rodents includes testing of rear foot reflexes before any incision is made, and continual observation of respiratory pattern, mucous membrane color and responsiveness to manipulations throughout the procedure. Rectal temperature and heart rate are monitored electronically during long or involved procedures.

Injectable anesthetics are typically administered by intraperitoneal route. Injectable analgesics and reversal agents are often administered by the subcutaneous or the intraperitoneal route. Intramuscular injections must generally be avoided because of the small muscle mass. Diluting drugs in sterile saline solution will make it easier to accurately measure volume for injection. It may also make some drugs less irritating when injected. Dilution may decrease shelf-life; the LARC standard is to discard drugs within one month of dilution. Vials containing sterle, diluted drugs must be labeled with the contents and the expiration date.

Ketamine-xylazine and ketamine-medetomidine combinations produce short-duration surgical anesthesia in larger species, but are frequently insufficient for major surgical procedures in many strains of mice. An excellent approach is to use a ketamine combination, but then titrate to effect with isoflurane from a precision vaporizer. Safety and efficacy should be demonstrated in a pilot group of animals before a large-scale study is initiated. Partial reversal of the xylazine or medetomidine using yohimbine or atipamezole is possible, and will restore cardiovascular staus more quickly. See: Dissociative Anesthetics

Mice are nocturnal animals, and are frequently housed in groups of nearly identical animals. These two factors make diagnosis of mild to moderate pain challenging. Weight loss is frequently monitored in animals at risk for ongoing pain. Pre-emptive treatment of pain before signs of pain are obvious is recommended.

Isoflurane provides no post-operative pain relief. If used for surgery, concurrent and follow-up use of ketamine and/or buprenorphine and/or a non-steroidal anti-inflammatory will be necessary. LARC veterinary staff recommend injecting the analgesic 30 minutes prior to the start of surgery.
See: Mouse Formulary

Rats

Rat anesthesia and analgesia considerations are similar to mouse anesthesia considerations, though some doses vary. In rats, ketamine combinations are more likely to provide adequate surgical anesthesia than in mice, and so may not require supplemental isoflurane. See: Dissociative Anesthetics, Inhalant Anesthetics, and, Rat Formulary

Hamsters

Hamster anesthesia is similar to rat and mouse anesthesia, though some anesthetic doses differ. Peripheral veins are extremely difficult to access in hamsters, limiting some of the anesthetic options.

Rabbits

UCSF works only with Pasteurella-negative rabbits, greatly reducing the risk of respiratory disease under anesthesia. Long procedures are best performed using inhalant anesthesia with an endotracheal tube in place. IACUC staff are available to train researchers in this technique. See: Rabbit Formulary

Guinea Pigs

Guinea pigs can be difficult to anesthetize, especially on a survival basis. Intravenous injection is difficult. Intramuscular injection is acceptable for non-survival procedures, though animals may self-mutilate at injection sites if they have recovered from anesthesia. Intraperitoneal (IP) administration works well, if the large cecum can be avoided. Guinea pigs may be anesthetized by face mask with volatile anesthetics; endotracheal intubation requires specialized training.

Cats

Cats are readily anesthetized using a variety of injectable or inhalant methods.

Initial restraint of a fractious or frightened cat can be a challenge for the researcher’s safety and for the animal’s welfare; choice of technique will depend on the skill level of the researchers as well as the individual cat’s temperament. Intravenous injection of a fractious cat requires a very high level of skill. Chamber induction with isoflurane can be stressful to the cat, and poses occupational exposure risk to the workers. Intramuscular or subcutaneous injection of sedatives requires a moderate level of skill, and carries some risk of cat bites and scratches. Training is available through the IACUC staff, and LARC veterinarians and veterinary technicians can provide direct assistance when necessary.

Non-steroidal anti-inflammatory drugs are useful, but must be used with caution in cats. Do not exceed recommended doses or frequencies of administration. Acetaminophen is never used with cats. See: Cat Formulary

Dogs

Dogs are easily anesthetized with a variety of techniques. Intramuscular injection of ketamine or ketamine combinations are to be avoided, because of the incidence of behavioral disturbances. See: Dog Formulary

Nonhuman Primates

Nonhuman primates require specialized handling and restraint to deliver anesthetics without compromising human safety. Ketamine or ketamine-midazolam are typically used by intramuscular injection for initial sedation. Once sedated, primates are easily anesthetized with a variety of techniques. Use of palatable oral medications decreases the need for restraint for medication. See: Nonhuman Primates Formulary

Swine

Swine are easily anesthetized with a variety of techniques. Ketamine-xylazine is a common intramuscular sedative, but requires a large volume of injection. Use of Telazol® or Telazol® combinations can significantly reduce the volume of injection for larger animals. See: Swine Formulary

Frogs

Immersion anesthetic (tricaine methanesulfonate, or MS-222) is common, especially for fully aquatic species like Xenopus. Once a surgical plane of anesthesia has been reached, anesthesia may be supplemented, but not eliminated, by maintaining the animal at 4o C. Post-operative pain management can include local infiltration of bupivicaine or with systemic xylazine. See: Local anesthetics

Sheep

Sheep anesthesia is challenging because of the animals’ large size and the unusual ruminant digestive physiology and anatomy. Adult sheep should have food withheld for 24-48 hours prior to general anesthesia, though they should be allowed access to water. Assessing anesthetic depth during constant-infusion ketamine anesthesia requires specialized training and, at UCSF, specialized certification by LARC veterinarians.

Fish

Immersion anesthetic (Tricaine methanesulfonate, or MS-222) is the most common anesthetic in use with fish

Birds

Small birds may be anesthetized by inhalation anesthetics (such as isoflurane) or injectable. Fasting is not generally required in advance. It is vital to maintain adequate warmth during the anesthetic period.