Sevoflurane


Sevoflurane is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset and offset.

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia, across all ages, as well as in veterinary medicine. Together with desflurane, sevoflurane is replacing isoflurane and halothane in modern anesthesiology. It is often administered in a mixture of nitrous oxide and oxygen.
Sevoflurane has an excellent safety record, but is under review for potential neurotoxicity, especially relevant to administration in infants and children, and rare reports similar to halothane hepatotoxicity. Sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.
Sevoflurane was discovered by Ross Terrell and independently by Bernard M Regan. A detailed report of its development and properties appeared in 1975 in a paper authored by Richard Wallin, Bernard Regan, Martha Napoli and Ivan Stern. It was introduced into clinical practice initially in Japan in 1990 by Maruishi Pharmaceutical Co., Ltd. Osaka, Japan. The rights for sevoflurane worldwide were held by AbbVie. It is now available as a generic drug.
Sevoflurane is an inhaled anaesthetic that is often used to put children asleep for surgery. During the process of waking up from the medication, it has been known to cause agitation and delirium. It is not clear if this can be prevented.

Adverse effects

Studies examining a current significant health concern, anesthetic-induced neurotoxicity are "fraught with confounders, and many are underpowered statistically", and so are argued to need "further data... to either support or refute the potential connection".
Concern regarding the safety of anaesthesia is especially acute with regard to children and infants, where preclinical evidence from relevant animal models suggest that common clinically important agents, including sevoflurane, may be neurotoxic to the developing brain, and so cause neurobehavioural abnormalities in the long term; two large-scale clinical studies were ongoing as of 2010, in hope of supplying "significant information" on neurodevelopmental effects of general anaesthesia in infants and young children, including where sevoflurane is used.

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. Sevoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. However, it also acts as an NMDA receptor antagonist, potentiates glycine receptor currents, and inhibits nAChR and 5-HT3 receptor currents.

Physical properties