Isoflurane: the need for new volatile agents

Clinical trials of isoflurane are about to start in the United Kingdom, and its product licence is imminent. Anaesthetists may well question the advisability of introducing a new and expensive volatile agent into clinical practice--especially a t a time of economic uncertainty in the NHS. Isoflurane, as yet unpriced in the UK, is certainly going to be more expensive than enflurane, mainly because it is a difficult compound to synthesise, but additionally because toxicity studies are becoming very expensive. In the case of isoflurane these have been protracted. Should anaesthetists recently equipped with expensive vaporizers for enflurane think twice about repeating the process for isoflurane? There are on the other hand several good reasons why isoflurane should become widely available in this country. One important argument in its favour is that an alternative to halothane is essential in everyday practice, because of the risk, albeit rare, of hepatic damage. An alternative should preferably produce anaesthetic conditions as smoothly as the older drug. In this role enflurane has not lived up to early expectations. Intravenous alternatives to halothane are available, but these are not necessarily the easiest techniques to use in casualty or outpatient departments. The discovery of the reductive metabolic pathway for h a l ~ t h a n e , ' ~ and the results of subsequent studies using hypoxic rat liver models, looked as though they were going to provide an explanation for halothane-associated hepatitis4. The issue does not now, however, appear to be quite so ~traightforward.~, ' Whether such liver damage is caused by a combined metabolic-immunological phenomenon or notl a drug of which only some 0.2% is metabolised, such as isoflurane, must have a very low potential for causing organ toxicity. (Some 20% halothane and 2% enflurane are metabolised). The physical properties of isoflurane are such that faster induction and recovery times than are currently possible should be attainable. However, isoflurane is an ether, so i t has a pungent smell, and slows gaseous induction to a time similar to, or longer than, that achieved with halothane. Recovery, though, is fast which could be an attractive feature in UK practice where large numbers of day-case and outpatient anaesthetics are administered. The dysrhythmogenic thresholds for isoflurane in the presence of exogeneous catecholamines have been predictably established-this was not possible with enflurane.8 It may well, therefore, become the agent of choice for oral surgery or where infiltration of tissues with solutions containing adrenaline is commonplace. lsoflurane produces a dose-dependent depression of the cardiovascular system, as d o halothane and enflurane, but unlike the isomer' studies a t multiples of minimum alveolar concentration were possible in volunteers. However, the tachycardia often seen with isoflurane may limit its use in hypotensive techniques, as its predominsnt effect on systemic vascular resistance may potentially increase blood loss from capillary beds. Whether these are purely theoretical points with little clinical significance, has yet to be established. Dr Eger, an initial investigator and then staunch champion of the drug when work by Corbett seemed to indicate that isoflurane was carcinogenicl0V1 has written a compendium on isoflurane.' * This is a readable, authoritative and excellent guide to the isoflurane literature. What place will isoflurane find in U K anaesthetic practice, where techniques which involve spontaneous breathing are extensively used? The factors already mentioned and the differences between isoflurane and other currently available volatile agents mean that isoflurane is well worthy of serious consideration. The initial cost of the new drug ought not to be a major factor if it is to fail to displace its isomer as the acceptable alternative to halothane. The use of low flow systems can markedly reduce the consumption of volatile agents and the latter have the additional benefit of reducing pollution in our working environment. I. M. CORALL