Animal anaesthesia: public sins and possible solutions
Paul Flecknell
Medical School, Comparative Biology Centre, Framlington Place, Newcastle, U.K.
Research workers normally aim to use an anaesthetic regimen that provides effective anaesthesia and analgesia, and which is appropriate for the purposes of their study. Given the wide range of species used in research and the different requirements of particular research projects, it is clear that there can be no single 'best' anaesthetic regimen. However, in all situations the aim should be to select an anaesthetic regimen that is effective. Although the vast majority of scientific papers report the use of appropriate anesthetic regimens in their materials and methods section, a minority of papers appear to use inappropriate techniques. Examples include:
Use of anaesthetic agents that are unlikely to provide an appropriate depth of anaesthesia in the species concerned - for example ketamine used as the sole anaesthetic in rodents.
Use of anaesthetic techniques that are highly unlikely to provide either loss of consciousness or analgesia - for example nitrous oxide combined with a neuromuscular blocking agent to immobilize the animal
Often, these problems seem to arise because of direct extrapolation of anaesthetic regimens between man and animals. In some circumstances this can be done effectively, but often species variation in drug responses are ignored. For example, midazolam and other benzodiazepines can produce loss of consciousness in man after intravenous administration. In dogs, even at high doses, they do not produce loss of consciousness and may cause agitation and excitement. High doses of potent opioids such as fentanyl and sufentanil produce loss of consciousness, as well as analgesia, in man, but in many animal species only analgesia is produced.
Other problems are less immediately apparent, but arise as a result of the small body size and high metabolic rate of laboratory rodents and rabbits. Several of these species require relatively high dose rates of anaesthetic combinations such as ketamine and medetomidine. These drugs are produced as fixed concentration formulations, and the agents may be given intramuscularly. This can result in relatively high volumes of anaesthetic agent being administered, for example 0.1ml to a 100g hamster - would a person tolerate 70ml given intramuscularly? This problem can be addressed by using the subcutaneous or intraperitoneal routes, although care must still be taken that the anaesthetic agents are not irritant.
Many of the problems mentioned above arise because of a failure to consult the appropriate scientific literature, or to seek expert advice. This is an issue that should be addressed both by national and institutional ethics committees and by those reviewing and editing scientific publications. Resolving these problems requires that research workers become more aware of the potential difficulties that may be encountered when anaesthetizing laboratory animals. Although training of new investigators is now widespread in Europe, many scientists have not attended any formal training courses. In any event, the level of training is very basic, and is unlikely to provide sufficient information to deal with these complex problems. Providing additional specialist advice, by developing the role of laboratory animal specialists, may prove much more effective. Anaesthesia should, by its very nature, represent an effective refinement of research procedures. It is essential, however, that the most appropriate techniques are used, both to ensure the welfare of the animals used, and to provide reliable and reproducible scientific data.
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