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

I. OVERVIEW: STANDARD OF CARE IN ANIMAL PAIN MANAGEMENT

Animal anesthesia, analgesia and pain management are crucial components of the animal use protocol. The standard of care at UCSF is to prevent animal pain whenever possible and to treat animal pain whenever diagnosed. Exceptions to these principles are permitted only in the minority of protocols approved by the Institutional Animal Care and Use Committee as USDA Category E (currently UCSF IACUC Category C).

Multi-modal anesthetic and analgesic regimens combine drugs from a variety of classes. They are designed to maximize the desired effects while minimizing those unhealthy side effects that occur with over-reliance on a single agent.

The ideal anesthetic/analgesic regimen

The ideal anesthetic/analgesic regimen must balance several goals:

1. It should provide pre-emptive analgesia so that animal pain is already being treated as the general anesthetic is wearing off, to prevent sensitization (“ramp-up”) of pain sensory mechanisms, and to lower the overall amount of general anesthetic required for the procedure.
2. It should be precisely titratable to assure that animals receive adequate anesthesia to block pain sensation, to produce unconsciousness, and to produce immobility without experiencing hemodynamic instability or life-threatening anesthetic overdoses.
3. It should not interfere with the study that the animals are on.
4. It should not result in unhealthy post-operative side-effects.
5. It should not cause pain or distress on induction or recovery
6. It should be compatible with available equipment and available medications

To meet the first goal, LARC and IACUC advocate pre-emptive analgesia, using some combination of four drug classes 30 minutes or more prior to the start of surgery. The four classes of injectable drugs are:

• opioid analgesics (such as buprenorphine);
• non-steroidal anti-inflammatory drugs (such as carprofen, meloxicam, ibuprofen);
• dissociative anesthetic/sedatives (ketamine, tiletamine)
• local/regional anesthetics (lidocaine, bupivicaine, proparacaine)

The disadvantages of this approach are that they add pre-anesthetic injection that may be distressful to the animals, that some drugs may slow anesthesia recovery, and that some are Controlled Substances requiring special storage and records keeping.

Volatile anesthetics (isoflurane, halothane, sevoflurane) delivered via a precision vaporizer best meet the second goal. Adjusting the inhaled percentage of anesthetic gas to deepen anesthesia is far safer than repeated redosing of injected drugs. Volatile anesthetics are easier to decrease as well, even compared to drugs for which there is an injectable antagonist or reversal agent. A major shortcoming of the inhalant anesthetic agents is the lack of residual analgesia once the vaporizer has been turned off.

The very best anesthetic plans are only as good as the skill and care with which they are applied. Training is available from the IACUC training and compliance staff [link to Training info]. Veterinary consultation is encouraged when planning any potentially painful study (and is required by law for USDA-covered species).

Drug dosages and frequencies of administration

Drugs should be listed in the protocol with approximate dose ranges. These are starting points which must be titrated up or down for the individual animal, or for the particular application (procedures conducted, animal age and strain differences). When laboratory experience finds that recommended dose ranges are consistently too high or too low for the particular application, the veterinarian should be informed, and a protocol modification submitted to the Institutional Animal Care and Use Committee.

Anesthetics are always titrated to effect. It is not acceptable to conduct surgical procedures unless the animal is fully anesthetized.

Analgesic doses and frequencies are more difficult to gauge. Caution is required for overnight pain management. Most analgesics administered at 5 pm will not still be effective at 8 am the next morning. Newer, longer-lasting non-steroidal anti-inflammatory analgesics may have longer durations of action than available opioids; they are frequently co-administered with an opioid to combine potency of effect with duration of action.

Safe and effective animal anesthesia

General guidelines on use of anesthetics and analgesics are posted. Plans for intra- and post-operative monitoring must be included in the IACUC protocol application, and then practiced as written.

Animals should be acclimated to their surroundings for several days prior to major procedures. Supplemental administration of warmed fluids (lactated ringers solution or isotonic saline) and maintenance of body temperature will improve anesthetic safety for the animals.