Guidelines for the Use of Analgesics and Tranquilizers in Laboratory Animal
What is Anesthesia?
Anesthesia is a state of unconsciousness induced in an animal. The three components of anesthesia are analgesia (pain relief), amnesia (loss of memory) and immobilization. The drugs used to achieve anesthesia usually have varying effects in each of these areas. Some drugs may be used individually to achieve all three. Others have only analgesic or sedative properties and may be used individually for these purposes or in combination with other drugs to achieve full anesthesia.
Curariform skeletal muscle relaxants or neuromuscular blockers (e.g. succinylcholine, decamethonium, curare, gallamine, pancuronium) are not anesthetics and have no analgesic effects. They may only be used in conjunction with general anesthetics. Normally, artificial respiration must be provided. Physiologic monitoring methods must also be used to assess anesthetic depth, as normal reflex methods will not be reliable.
It is important to realize that anesthesia is not a simple thing. It has profound effects on an animal's physiology because of the generalized central nervous system effects as well as specific effects on all other body systems. Thus, while anesthesia is necessary to prevent pain or distress in research animals, it must not be ventured into lightly. It is important to learn about the drugs you will be using and about the physiology of the animal you will be monitoring. Specific anesthetic drugs and their use are detailed below. All drug dosages are listed in RAR's formulary.
Intra-operative and Anesthesia Records
The Guide for the Care and Use of Laboratory Animals and the Institutional Animal Care and Use Committee Guidebook require that animals under anesthesia be carefully monitored to insure adequate depth of anesthesia, animal homeostasis, timely attention to problems, and support during anesthetic recovery. Monitoring includes, but is not limited to, checking anesthetic depth and physiological parameters (minimum: heart rate and respiratory rate) on a regular basis (minimum every 10 minutes).
Record keeping is an essential component of peri-operative care. For major surgical procedures on non-rodent mammals, an intra-operative anesthetic record must be kept and included with the surgeon抯 report as part of the animal抯 records. In addition to the above requirements, the record should include all drugs administered to the animal, noting the dose, time, and route of administration. These records should be available to RAR and any other personnel providing post-operative care. Although it is not required, RAR strongly encourages the use of an intra-operative rodent anesthetic record during surgical procedures.
The required monitoring will vary according to the species and the complexity of the procedure, but should include:
A pre-surgical assessment;
Adequate monitoring of anesthetic depth and homeostasis
Support such as fluid supplementation, external heat, or ventilation
Monitoring and support during anesthetic recovery
Post-operative monitoring (provided by RAR for all large animals)
The following are suggestions from the American College of Veterinary Anesthesiology for monitoring anesthetized animals:
Circulation: to ensure that blood flow to the tissues is adequate.
Methods: Heart rate, Palpation of peripheral pulses, ECG, auscultation of heartbeat, non-invasive or invasive blood pressure monitoring.
Oxygenation: to ensure adequate oxygen concentration in the animal抯 arterial blood.
Methods: observation of mucous membranes color and CRT, pulse oximetry, blood gas analysis
Ventilation: to ensure that the animal抯 ventilation is adequately maintained.
Methods: respiratory rate, observation of thoracic wall movement or breathing bag movement if animal is spontaneously breathing, ascultation of breath sounds, respiratory monitor, capnography, blood gas monitoring.
What is Analgesia?
Analgesia is the relief of pain. Pain is normally defined as an unpleasant sensory and emotional experience associated with potential or actual tissue damage. Pain is difficult to assess in animlas because of the inability to communicate directly about what the animal is experiencing. Instead, indirect signs of pain are often used. Because of the difficulty of determining when an animal is in pain, animal welfare regulations require that analgesia be provided whenever a procedure is being performed or a condition is present that is likely to cause pain. In the absence of evidence to the contrary, it is assumed that something that is painful in a human will also be painful in an animal. It is best if analgesia can be provided to animals preemptively, or prior to the painful procedure, rather than waiting until after clinical signs of pain are observed. Analgesia is normally provided using one of several types of pharmaceutical preparations.
GeneralInhalation anesthesia is superior to most injectable forms of anesthesia in safety and efficacy. It is easy to adjust the anesthetic depth. Because the anesthetics are eliminated from the blood by exhalation, with less reliance on drug metabolism to remove the drug from the body, there is less chance for drug-induced toxicity. Inhalation anesthetics are always administered to effect, because the dosage can vary greatly among individual animals and different animal species. The disadvantages to inhalant anesthesia are the complexity and cost of the equipment needed to administer the anesthesia, and potential hazards to personnel. All inhalant drugs are volatile liquids. They should not be stored in animal rooms because the vapors are either flammable or toxic to inhale over extended periods of time. In particular, ether must be stored in a proper hood or cabinet for flammable materials.
Inhalant Agents
Drug MAC Response Toxicity Comments Ether 3.2 slow liver Pre-medication with an anticholinergic may be necessary to reduce excessive respiratory secretions. Induction and recovery can be rough. Flammable and can become explosive with prolonged storage. Ether must be used according to appropriate safety guidelines. Chloroform A hazardous agent (carcinogenic) and cannot be used at U of M. Methoxyflurane 0.2 slow nephrotoxicity- is potentiated by tetracyclines It has good analgesic activity, but there is significant metabolism, ++ respiratory depression and + cardiac depression. This drug is not currently being manufactured. For a replacement, consider ether or diluted isoflurane. Halothane 0.9 moderate hepato- and nephrotoxicity if the animal is hypotensive ++ cardiopulmonary depresssion, and a risk of malignant hyperthermia in some breeds/strains Isoflurane 1.5 fast none ++ respiratory depression and + cardiovascular depression Enflurane 2.0 fast none ++ cardiopulmonary depression and minimal respiratory depression Nitrous Oxide 180 very fast hepatotoxic Cannot be used as a sole anesthetic agent. Do not exceed a 50% mix w/ oxygen and other inhalant agent to prevent hypoxia. Moderate analgesia is provided by nitrous. In general, use of nitrous oxide in animals is discouraged. Carbon Dioxide (CO2) 50-70 very fast cerebral anoxia Can be used as an anesthetic for brief procedures and as a euthanasia agent. It has antinociceptive activity and causes unconsciousness prior to hypoxia. It is necessary to monitor carefully and work quickly, as animals die quickly (1-2 min) after losing consciousness, and likewise they wake up quickly when exposed to room air. Appropriate for quick procedures such as tail snipping, ear marking and orbital bleeding. Poses minimal hazard to personnel and can be used in laboratories or animal room MAC: This is the % concentration of the drug needed to anesthetize 50% of animals. It does vary somewhat by species and by individual. 1.2X MAC is an approximate vaporizer setting for maintenance of anesthesia. Induction generally requires 2-3X MAC. MAC listed here is for rats (ether), mice (CO2), goat (enflurane) and dogs (all others).
Response. This refers to how rapidly concentrations in the blood change when the lung alveolar concentration is changed. Slow anesthetics have slow induction and recovery times.
Toxicity: Drugs that are metabolized by the body can cause toxicity, especially if a pre-existing organ dysfunction exists.
Injectable Anesthetics, Analgesics and Sedatives
Phenothiazine and Buterophenone Sedatives (Acepromazine)
Benzodiazapines (Diazepam, midazolam)
Thiazines (Xylazine and medetomidine)
Dissociative Anesthetics (Ketamine and Telazol)
Other Anesthetics (Alpha Chloralose, Tribromoethanol, Urethane)
