Sevoflurane and isoflurane are both from the halogenated ether group of inhalational anaesthetic agents and both agents are indicated for the induction and maintenance of general anaesthesia. Isoflurane is currently licensed in the UK for use in dogs, cats, horses, ornamental birds, reptiles and small mammals including rabbits, whilst sevoflurane is still currently only licensed for use in dogs.
Both isoflurane and sevoflurane cause similar side effects including dose-dependent depression of the central nervous system, respiratory depression, depression of body temperature regulating centers, hypotension, vasodilation, myocardial depression and muscle relaxation. Both agents can cause a reduction in cerebral metabolic rate whilst also causing vasodilation and therefore a potential increase in cerebral pressure. This should be closely monitored in patients with head trauma and/or cerebral disease, and it may be necessary to ventilate them to ensure carbon dioxide levels are kept at an appropriate level to prevent a further rise in cerebral pressure. One study has demonstrated that a group of dogs had less respiratory depression with sevoflurane when given equipotent doses of sevoflurane and isoflurane. No studies have demonstrated one agent to be superior to the other in terms of overall side effects.
As a guide the minimum alveolar concentration (MAC) for isoflurane is approximately 1.3% in the dog and 1.6% in the cat. This is considerably lower than the MAC of sevoflurane at approximately 2.4% in both species. When you consider that surgical anaesthesia is normally achieved at 1.5 times MAC it becomes clear that a considerably higher vaporiser setting will be required when using sevoflurane compared to if the same patient were anaesthetised using isoflurane. This means that proportionally more sevoflurane will be used to ensure the patient remains at an adequate depth for surgery. In real terms if using the same fresh gas flow rate more sevoflurane will be used, making it a less economical option.
The blood-gas solubility of sevoflurane is lower than that of isoflurane. This difference is not as great as the difference between isoflurane and halothane. However, the lower the blood-gas solubility, the more rapidly the agent achieves an effect in the brain and in turn the quicker the drug is released from the brain. This means that induction and recovery should be more rapid with sevoflurane as compared to isoflurane and that changes in vaporiser setting should provide a more rapid change in anaesthetic depth. This rapid change in depth in response to a change in the inspired anaesthetic concentration could indeed be an advantage of sevoflurane, especially in critical patients whose vital statistics and anaesthetic depth can be closely monitored by a competent anaesthetist. However, if the patient cannot be monitored closely or a trained anaesthetist is not at hand to respond to changes in anaesthetic depth then this drug should be used with respect. Unfamiliarity with this agent and monitoring that is not thorough enough can often lead to the patient becoming 'too deep' very quickly and to a tendency to have the animal anaesthetised slightly 'deeper' than is ideal. This can give rise to problems as there are few margins for error when patients become overdosed especially when they are critically ill. Remember 'there are no such things as safe anaesthetic drugs only safe anaesthetists!' It is worth noting that the onset of, and indeed recovery from, side effects will also be seen more quickly with the use of sevoflurane compared with isoflurane.
Other factors will also contribute to the recovery from anaesthesia and changes in anaesthetic depth. These include the other drugs used concurrently in the anaesthesia protocol, the patient's body fat ratio, the patient's disease state and the overall metabolism of the patient. For example a patient with a very high metabolism will quickly recover from either inhalant agent and the blood-gas solubility becomes less of an influencing factor. In the author's opinion the recovery from sevoflurane compared to isoflurane in a clinical situation is generally only a few minutes faster and often does not make a dramatic difference to recovery, especially in healthy patients.
Both sevoflurane and isoflurane are mainly eliminated from the body through respiration following the cessation of anaesthesia and in both cases there is only a small percentage of the drug metabolised by the liver and then excreted by the kidneys.
The lower blood-gas solubility makes sevoflurane an ideal choice for masked induction as the onset of anaesthesia will be faster than that seen with isoflurane. In addition isoflurane has a marked and pungent smell and can be an airway irritant when used for induction of anaesthesia using chambers and masks. For this reason it is generally less well tolerated than the odourless inhalant agent sevoflurane. Sevoflurane does not appear to cause airway irritation.
Sevoflurane is relatively expensive compared to isoflurane currently; although, as the demand from the veterinary market rises, especially following the gradual withdrawal of halothane, the cost could potentially fall making it more affordable and comparable in cost to the cheaper agent isoflurane. It should be noted that sevoflurane can be made more cost effective by using a low-flow anaesthetic technique; although this requires careful monitoring and more monitoring equipment. This is also true of isoflurane, so if used on a like-for-like basis sevoflurane is still considerably more expensive. It should be noted that using low-flow anaesthesia reduces the rate at which the vaporiser setting affects the inhaled levels of anaesthetic gas, thus negating some of sevofluranes advantages over isoflurane.
Sevoflurane has been demonstrated to produce 1,1,3,3,3-pentafluoro-2-(fluoromethoxy)propene, also known as compound A when it interacts with soda lime. Compound A has been shown to cause nephrotoxicity in rats; however, the mechanism of this is unknown and this finding has not been demonstrated in dogs. The concentration of compound A increases in a circle system, with increasing sevoflurane levels and decreasing fresh gas flow rates, and for this reason the manufacturer's data sheet advises avoiding long-duration, low-flow anaesthesia with sevoflurane.
Conclusion
Whilst the development and licensing of sevoflurane for the veterinary market obviously may have some benefits in the anaesthesia of critical patients, due to the more rapid change in anaesthetic depth, isoflurane is still the licensed drug for many species and should be considered under the VMD regulations and under the prescribing cascade. As sevoflurane becomes more affordable and potentially may be licensed for a greater variety of species it could be a valuable addition to veterinary anaesthesia. Currently in dogs it provides the option of masked induction of anaesthesia, providing rapid onset of anaesthesia.
There is also no doubt that sevoflurane will give a small percentage increase in recovery times and faster changes in anaesthetic depth than isoflurane but the actual clinical relevance of this is not clear. Rapid recovery may certainly be of benefit but rapid does not necessarily equal smooth, which in many cases is just as important; there are other factors besides the inhalant agent that will affect this, notably sedative premedicants and analgesia. It should at this point be noted that a balanced anaesthetic isn't just about the inhalant and induction agents.
Despite the given advantages of sevoflurane isoflurane should not be discounted as a valuable resource in small animal anaesthesia; despite the pungent smell and irritability to airways if used for masked induction, it causes no problems in this area when used for maintenance of anaesthesia. The difference in blood-gas solubility is not so vastly great that it will make a huge difference in healthy patients undergoing routine surgery. However, the author accepts that for critical canine cases sevoflurane may be advantageous providing the anaesthetist is experienced in its use.
References
1. Flecknall P, Waterman-Pearson A. Pain management in animals. London: WB Saunders, 2000.
2. Lumb W, Jones E, et al. Lumb & Jones' veterinary anesthesia (third edition). Philadelphia: Lippincott Williams & Wilkins, 1996.
3. McKelvey D, Hollingshead KW. Veterinary anesthesia and analgesia (third edition). St Louis: Mosby, 2003.
4. Muir W, Hubbell J, et al. Handbook of veterinary anesthesia (fourth edition). St Louis: Mosby, 2007.
5. Welsh E. Anaesthesia for veterinary nurses. Oxford: Blackwell Publishing, 2003.