Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia.

Sevoflurane is an ether inhalation general anaesthetic agent with lower solubility in blood than isoflurane or halothane but not desflurane. The low solubility and the absence of pungency facilitate rapid mask induction; the low blood solubility also expedites "wash-out' and therefore recovery from anaesthesia. Sevoflurane produces dose-dependent CNS, cardiovascular and respiratory depressant effects that generally parallel those of isoflurane. Sevoflurane is degraded by carbon dioxide absorbents to nephrontoxic (in rats) haloalkenes, although renal toxicity has not been observed in humans. Compared with other inhalation anaesthetics, negligible quantities of carbon monoxide are generated from degradation of sevoflurane by carbon dioxide absorbents. Sevoflurane has negligible airway irritant effects, which facilitates a "smooth' induction, even in comparison with halothane in paediatric patients, and makes sevoflurane especially amenable to rapid induction of anaesthesia in adults and children. Emergence, orientation an postoperative cognitive and psychomotor function recovery of paediatric outpatients is singnificantly more rapid from sevoflurane than from halothane anaesthesia. In adult inpatients and outpatients, emergence and orientation are significantly faster after sevoflurane than after isoflurane but not desflurane anaesthesia. Other recovery parameters (e.g. times to sitting, ambulation) occur at similar times after either sevoflurane or desflurane anaesthesia. Recovery of psychomotor function occurs at generally similar times after sevoflurane, isoflurane or desflurane. Compared with propofol, sevoflurane facilitates more predictable extubation times and significantly better postoperative modified Aldrete scores in outpatients, although cognitive and psychomotor recovery occurs at similar times for both agents. As a supplement to opioid anaesthesia during coronary bypass graft surgery or in those at risk for myocardial ischaemia, sevoflurane is comparable to isoflurane. Limited data suggest that it is also as useful as isoflurane for the maintenance of anaesthesia during neurosurgical or obstetric procedures. Sevoflurane is well tolerated by adult and paediatric patients during induction of anaesthesia, with a low incidence of mild airway complications (breath-holding, coughing, excitement and laryngospasm). During rapid induction, it is particularly better tolerated than isoflurane or halothane. Sevoflurane has a lower potential for hepatic injury than halothane. Unlike methoxyflurane, sevoflurane undergoes minimal intrarenal defluorination, which may account for the lack of fluoride ion-induced nephrotoxicity in humans, despite elevated plasma fluoride levels after its use. In summary, sevoflurane provides for a rapid and smooth induction of, and recovery from, anaesthesia. These features combined with its favourable cardiovascular profile should make sevoflurane the agent of choice for inhalation induction in adult and paediatric anaesthesia. Although further clinical evaluation will define the role of this agent relative to that of propofol and desflurane, sevoflurane should also prove to be a valuable alternative anaesthetic agent for adults in both outpatient and inpatient surgery.