Sevoflurane

Sevoflurane (1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane; synonym, fluoromethyl hexafluoroisopropyl ether), is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. Sevoflurane's name derives from the seven fluorine atoms in its substituents, alongside a standard suffix for such agents.

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia, and including in anesthesia of children and infants, and 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.

After desflurane, it is the volatile anesthetic with the fastest onset and offset. Though desflurane has the lowest bloodâ€"gas partition coefficient of the currently used volatile anesthetics, sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.

Sevoflurane "has an excellent safety record", but is under review for potential neurotoxicity, especially relevant to administration in infants and children, and rare case reports akin to halothane hepatotoxicity, have made clear that low frequency liver injury may occur.

Sevoflurane was discovered by Ross Terrell. and independently by Bernard M Regan, Federation Proceedings Abstracts, 30 (2), 1374, 1971 First reports on the use of sevoflurane appeared in the literature in 1971; and 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 J of the International Anesthesia Research Society 54 (6), 1975 it was introduced into clinical practice initially in Japan in 1990. The rights for sevoflurane in the US and other countries were held by Abbott Laboratories; it is now available as a generic drug.

Medical uses

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

Sevoflurane raises intracranial pressure and can cause respiratory depression.

Studies examining a current significant health concern, anesthetic-induced neurotoxicity (including with sevoflurane, and especially with children and infants) 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 (PANDA and GAS) were ongoing as of 2010, in hope of supplying "significant [further] information" on neurodevelopmental effects of general anaesthesia in infants and young children, including where sevoflurane is used.

Pharmacology

Sevoflurane acts primarily as a positive allosteric modulator of the GABA_A receptor. However, it also acts as an NMDA receptor antagonist, potentiates glycine receptor currents, and inhibits nACh and 5-HT₃ receptor currents.

Physical properties

Bispectral index

Sevoflurane has lower values of controversial bispectral index than desflurane.

References

Further reading

• Patel SS, Goa KL (April 1996). "Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia". Drugs 51 (4): 658â€"700. doi:10.2165/00003495-199651040-00009. PMID 8706599. 
  "Erratum". Drugs 52 (2): 253. August 1996. doi:10.1007/bf03257493. 
• Wallin, Richard F., Regan, Bernard M., Napoli, Martha D., Stern, Ivan j. (Novâ€"Dec 1975). "Sevoflurane: A New Inhalational Anesthetic Agent". Anesthesia and Analgesia 54 (6): 758â€"766. doi:10.1213/00000539-197511000-00021. 

External links

• "Propofol and Sevoflurane Anesthesia". 

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