What is anaesthesia?
Anaesthesia is defined as “Loss of sensation” (Oxford English Dictionary). Anaesthesia can be produced either by blocking sensation to a particular region of the body (local or regional anaesthesia) or by the administration of drugs that produce a loss of consciousness (general anaesthetics). Most laboratory animals are anaesthetised using general anaesthetics, but local anaesthesia can also be useful. For example, local anaesthetic cream (EMLA, Astra) can be applied to the skin to prevent pain or discomfort associated with venepuncture.
Why anaesthetise an animal?
Laboratory animals may be anaesthetised for one or more different reasons, for example:
- To provide immobility, so the animal does not displace catheters or move during imaging procedures.
- To prevent pain during experimental procedures.
- To prevent distress during physical restraint
The depth of anaesthesia and the choice and dose of anaesthetic agent may vary depending upon which of these aims is to be achieved.
Why is it important to get it right?
Controlling unwanted variability is crucial to producing high-quality research data. An increased variation in your data caused by the use of an inappropriate anaesthetic technique, or by using a technique incorrectly may lead to an increased number of animals being required for the study. Increased mortality from poor anaesthetic technique will also increase the numbers of animals required for the study. Carefully planned anaesthesia and pain management can help you refine your study and reduce the number of animals you use.
Refinement and reduction are two key principles of the 3Rs ethical framework.
What are the 3Rs?
The 3Rs are a widely accepted ethical framework for conducting humane and high-quality animal experiments.
- Replacement – Methods which avoid or replace the use of animals.
- Reduction – Methods which reduce the number of animals used.
- Refinement – Methods which reduce to a minimum the pain and distress experienced by those animals which it is still necessary to use (after first reducing and replacing animals in your research).
Carefully planned anaesthesia is a crucial part of applying the principles of refinement and reduction to your research project.
When drafting project licences you will be asked to explain how you will address the 3Rs in your work. You will also be asked to explain why you will not be using analgesia if pain and distress is expected.
Is anaesthesia safe for the animal?
When we produce general anaesthesia, we depress activity in the brain and spinal cord, and this causes the animal to lose consciousness. At deeper levels of anaesthesia, the animal becomes insensible to painful stimuli.
We need to remember that other body systems, such as the heart and lungs may also be affected. Often, blood pressure falls and respiratory functions are impaired. If anaesthesia is too deep, the depression of these different body systems can be life-threatening.
To recognise when body systems are being depressed during anaesthesia, we can monitor the animal, and take measures to minimise these effects. For example we can give oxygen, or infuse fluids to support the circulation.
When may anaesthesia affect the outcomes of your study?
It is important to consider when anaesthesia may affect the outcome of your research work.
Before choosing an anaesthetic remember that most anaesthetics cause cardiovascular and respiratory depression and hypothermia. We can minimise these effects by careful selection of the anaesthetic regimen, using methods to reduce the dose of agent, and by providing support and monitoring.
Anaesthetics may also have specific, less obvious effects that can interact with particular research projects.
Alterations in immune function, metastatic rates of tumours, changes in organ blood flow distribution, competition for enzyme pathways, interaction with receptors and changes in gastrointestinal motility are examples of the types of interactions that can occur.
Minimising the likelihood of these issues occurring requires a careful review of the literature. It is important to appreciate that relying on previously published use of a particular anaesthetic with a particular animal model may not be appropriate, since the research workers conducting the earlier study may not have reviewed the literature critically.