Inhalational agents can be used to provide safe and effective anaesthesia in virtually all laboratory species. A number of different anaesthetic agents are available – isoflurane, desflurane, sevoflurane and nitrous oxide. Modern volatile anaesthetic agents are very potent. All are liquids at room temperature and vaporise readily, so they must be delivered using a purpose-made vaporiser.
The concentration of anaesthetic needed to induce and maintain anaesthesia varies between the different agents.
Table: Induction and Maintenance Concentrations of Inhalation Anaesthetic Agents| Anaesthetic | Concentration for induction of anaesthesia (%) | Concentration for maintenance (%) | Minimum alveolar concentration (indicates relative potency of different agents) (in rat) |
|---|---|---|---|
| Desflurane | 18 | 11 | 6.5 – 8 |
| Enflurane | 3 – 5 | 3 | 2.2 |
| Ether | 10 – 20 | 4 – 5 | 3.2 |
| Halothane | 4 | 1–2 | 0.95 |
| Isoflurane | 5 | 1.5 – 3 | 1.38 |
| Methoxyflurane | 3 | 0.4 – 1 | 0.22 |
| Nitrous oxide | – | – | 250 |
| Sevoflurane | 8 | 3.5 – 4.0 | 2.7 |
| Data shown for rat; some species variation occurs; data from Mazze et al. (1985), Steffey et al. (1974), Kashimoto et al. (1997), Gong et al. (1998) and Brosnan et al. (2007). | |||
Advantages of volatile anaesthetics
Provided that appropriate equipment is available, volatile anaesthetics offer many advantages when anaesthetising animals:
- They are simple to administer
- Induction (onset) of anaesthesia is usually smooth and rapid.
- It is easy to change the depth of anaesthesia
- Recovery is usually rapid (within 10-15 minutes) and uneventful
Disadvantages of volatile anaesthetics
Disadvantages include:
- The equipment needed for their safe use is relatively expensive
- It is usually possible to anaesthetise only one animal at a time
- Waste anaesthetic gases must be removed for health and safety reasons
Properties of specific agents
The most widely used agents are Isoflurane and Sevoflurane.
- Ether is no longer available as an anaesthetic agent in Europe or North America and since it is unpleasant for animals to inhale and also poses a safety risk (as it forms explosive mixtures with air or oxygen) it should not be used.
- Halothane was a suitable anaesthetic (see below) but it is no longer available commercially in many countries.
- Similarly, Methoxyflurane is now unavailable in most countries.
- Desflurane can be used for anaesthesia of laboratory animals, but it is significantly more expensive than the other agents that are available. It provides even more rapid onset and recovery from anaesthesia than do Sevoflurane and Isoflurane.
Isoflurane
Isoflurane produces very rapid induction and recovery from anaesthesia, and the depth of anaesthesia can be altered easily and rapidly. It is non-irritant, non-explosive and non-flammable. However its pungent odour has been reported to cause breath holding during induction in children, but this does not seem a significant problem in most species, with the exception of the rabbit and the guinea pig.
Isoflurane produces moderate respiratory and cardiovascular system depression.
The main advantage of using isoflurane in experimental animals is that it undergoes very little biotransformation and is almost completely eliminated in exhaled air. This suggests that there will be little effect on liver microsomal enzymes and, hence, minimal interference in drug metabolism or toxicology studies. This characteristic, together with the rapid induction and recovery from anaesthesia, has lead to the widespread adoption of isoflurane in many research establishments.
Sevoflurane
Sevoflurane produces even more rapid induction and recovery from anaesthesia than does isoflurane, and the depth of anaesthesia can be altered very easily and rapidly. It is non-explosive and non-flammable. Sevoflurane is much less pungent than other agents, and mask induction is well tolerated in many species (with the exception of rabbits and guinea pigs).
Sevoflurane is relatively expensive, and is unstable in the presence of soda lime, the carbon dioxide absorber used most commonly in closed-breathing system anaesthesia. The breakdown products can cause renal injury, but the concentrations produced are very low in normal circumstances. It is highly unlikely that significant toxicity will be encountered during use in laboratory animals.
The main advantage of sevoflurane is the even greater ease of matching the depth of anaesthesia to the degree of surgical stimulation, coupled with very rapid and smooth recovery. If undisturbed, many animals recover from sevoflurane without a period of involuntary excitement. In the author’s institute, it has been used with great success for very prolonged procedures, and also for very brief procedures when rapid induction and recovery are needed.
Desflurane
Desflurane produces more rapid onset and recovery from anaesthesia than any of the other volatiles anaesthetics. It also undergoes the least degree of metabolism. And is relatively non-irritant to inhale.
Desflurane is relatively expensive and requires a pressurized, temperature- controlled vaporizer because of its very low boiling point. This anaesthetic has not been widely used in either veterinary clinical practice or laboratory species.
Halothane
Halothane is easy to vaporise, and induction and recovery are rapid (1–3 minutes). It is a potent anaesthetic, is non-irritant and is neither flammable nor explosive. Some hepatic metabolism of halothane occurs, and marked liver microsomal enzyme induction may follow anaesthesia.
Halothane has a depressant effect on the cardiovascular system. Moderate hypotension is produced at surgical levels of anaesthesia because of a reduction in cardiac output and peripheral vasodilatation. A dose-dependent depression of respiration also occurs.
Halothane has been a popular agent for maintaining anaesthesia in most species. However, it is now rarely used in medical anaesthetic practice in Europe and North America, because of the introduction of newer agents, and as a result the manufacture of this agent has been discontinued. However, it will still be available from specialist sources and will continue to have an important role, particularly as an anaesthetic for neurophysiological studies.
Nitrous Oxide
Nitrous oxide causes minimal cardiovascular and respiratory system depression but has very low anaesthetic potency and cannot be used alone to produce anaesthesia, or even unconsciousness, in most species. It reacts with vitamin B12, producing vitamin depletion after prolonged (>6
Nitrous oxide is extensively used for anaesthesia in animals and humans, although the mechanisms of its anaesthetic and analgesic effects are still not fully characterised. Since nitrous oxide has minimal effects on the respiratory and cardiovascular systems, it can be used to reduce the required concentration of other agents and so to reduce the overall degree of depression of blood pressure or respiration at a particular depth of anaesthesia. It is usually administered as a 50:50 or a 60:40 mixture with oxygen. Using 60% nitrous oxide reduces the concentration of isoflurane needed for surgical anaesthesia in rodents from around 1.5-2% to 1.1-1.5%. Because of its low anaesthetic potency, nitrous oxide must never be used as the sole anaesthetic agent in association with neuromuscular blocking (NMB) agents such as pancuronium.
Its main value lies in reducing the required concentration of other more potent agents which have more marked side-effects. It is important to note that nitrous oxide is not absorbed by the activated charcoal used in some gas-scavenging systems. If nitrous oxide is used, then an active scavenging system that ducts expired gases directly to the room ventilation extract must be used.
A common misconception is that it is necessary to administer nitrous oxide in order to administer other inhalation anaesthetics. This is not the case, and all of the other agents mentioned above can safely be administered in 100% oxygen. It is only necessary to avoid this if prolonged periods of anaesthesia are planned (>12–24 hours), when the inspired oxygen concentration should be reduced (to approximately 40%) to avoid the possible development of oxygen toxicity. This can be achieved without the use of nitrous oxide by using an air/oxygen or nitrogen/oxygen mixture, the other gas being supplied from an appropriate compressed gas cylinder. If the gases are mixed at the outlet from the anaesthetic machine, then the delivered concentration of anaesthetic vapour will be reduced, and the vaporizer setting should be increased accordingly. This approach can also be used when the inspired concentration of oxygen needs to be reduced because of the requirements of a specific research protocol (e.g. models of stroke).