Key Principles

Animals are anesthetized to provide analgesia and lack of awareness so that painful procedures can be undertaken humanely (e.g., surgery). Anesthesia can also provide a means of restraining an animal so that it is not distressed by prolonged immobilisation, for example, as required for Magnetic Resonance Imaging (MRI). The use of safe and effective anesthesia is an important refinement of research procedures, but anesthetic methods must be selected carefully and regularly reviewed.

Anesthetic management includes all the processes and events during a period of anesthesia that will result in freedom from pain during an invasive procedure and a return to a normal physiological state after recovery. Choosing the best anesthetic for a particular research project is not straightforward. Non-veterinary users should always consult with a veterinary anesthesiologist or laboratory animal veterinarian prior to using such drugs.

In general, an anesthetic agent should:

  • achieve the required depth and duration of anesthesia
  • be simple to administer, without causing significant distress to the animal
  • be free from undesirable side effects and allow a smooth and uncomplicated recovery
  • cause minimal interference with the purpose of the research procedure

The veterinarian will consider a number of animal-related factors when choosing the type of anesthetic agent. For example:

  • Species - Different species require different doses of anesthetic agents. Familiarity with the effects of an anesthetic agent in one species should not be assumed in another species.
  • Strain - Strain differences have been noted, even within the same species (e.g., some strains of pigs are more susceptible to malignant hyperthermia during halothane anesthesia than others).
  • Age - Young animals and old animals may have an increased risk for anesthetic complications.
  • Weight - During anesthesia, very fat animals may not breathe as effectively as thinner animals, leading to problems associated with hypoventilation. If the amount of the agent is based on the weight of the animal (i.e. mg/kg), there may be a relative overdose because fat has poorer blood circulation than muscle.  Animals with very little fat may experience longer than usual recovery from anesthesia.
  • Sex - There is evidence for a difference between the sexes for some anesthetics.
  • Health - Pre-existing disease or pathology may complicate anesthesia (e.g., lung disease may compromise respiration during anesthesia, and liver disease may interfere with the metabolism of anesthetic agents).
  • Demeanor - An exited animal with high levels of circulating adrenalin and elevated heart rate and blood pressure is at an increased risk when undergoing anesthesia.
  • Previous anesthesia - Some injectable anesthetics are not completely cleared from the body for several days (e.g., pentobarbital), and care must be taken if a second anesthetic is administered soon after the first. For those anesthetics that are extensively metabolized as part of the excretory process, a second anesthetic may be more rapidly metabolized than the first, with a shorter period of anesthesia.
  • Drug interactions - Some non-anesthetic drugs have effects on anesthetic agents.

Animal Welfare Considerations

Prior to anesthesia, particular care should be taken to handle the animal gently and calmly in order to minimize struggling and fright. Prolonged excitement will disturb the circulatory and metabolic state of the animal and induce a degree of shock. Furthermore, attempting to anesthetize a struggling animal is physically difficult, and distress during handling can increase the likelihood of an abnormal response to the anesthetic agents. Therefore, the use of pre-anesthetic agents (e.g., sedatives and tranquillizers) should be considered to:

  • reduce apprehension in the animal
  • allow a reduction in the dose of anesthetic required
  • reduce some of the side effects of the anesthetic agent
  • provide some analgesia after the anesthetic has worn off

Use of Neuromuscular Blocking Drugs

Historically, neuromuscular blocking drugs (paralyzing agents) were used as an adjunct to anesthetics to provide greater muscle relaxation during a surgical procedure, or when control of respiration was necessary. These agents provide no sedation or analgesia. The paralysis created by neuromuscular blocking agents abolishes some of the signs used to judge the depth of anesthesia. Thus, an animal may appear to be anesthetized (i.e. unresponsive to any painful stimuli) while in reality, it is unable to respond because of the muscle paralysis. This scenario represents an unacceptable compromise to animal welfare. To decrease this risk to animal welfare and to further refine experimental protocols, researchers using neuromuscular blocking drugs should work with their institution's veterinarian to find alternative anesthetic regimes.

Side Effects

Anesthetic agents frequently affect the cardiovascular, respiratory and thermoregulatory mechanisms, in addition to the central nervous system (CNS), and have side effects that may not be desirable. Every effort should therefore be made to maintain the circulation, respiratory function and body temperature of the anesthetized animal within normal physiological limits. Side effects can include:

  • Central Nervous System (CNS) depression - The commonly used anesthetics provide CNS depression to the point of loss of consciousness, and many of the reflexes that are used to assess anesthetic depth are retained after unconsciousness. However, if anesthetic depth increases, these are gradually lost and even automatic functions like respiration may be lost.
  • Cardiovascular depression - Anesthetics usually cause a decrease in cardiac output and a fall in blood pressure.
  • Respiratory depression - One of the effects of anesthetic agents is to cause a loss of muscle tone and a decrease in contractility. The overall effect is to reduce the respiratory capability of the animal.
  • Loss of temperature control - Anesthetic agents inhibit the mechanisms responsible for maintaining a steady body temperature, including the temperature regulating centres in the brain and processes like shivering. Hypothermia is a major consideration in anesthesia, especially for small animals such as rodents, and controlled supplemental heat must be provided to maintain body temperature.
  • Hormone release depression - Generally, the release of hormones is depressed. Prolactin release may be increased by some general anesthetics.
  • Depression of other functions - Gastro-intestinal motility is depressed by general anesthetics, as is liver function. Urinary excretion is decreased.

This section was adapted from material on the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) website and CCAC guidance documents.

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