|Systematic (IUPAC) name|
|Trade names||Sojourn, Ultane, Sevorane|
|Legal status||POM (UK) ℞-only (US)|
|Mol. mass||200.055 g/mol|
|(what is this?)|
Sevoflurane (1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane), also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it 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 blood/gas coefficient of the currently used volatile anesthetics, sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.
First reports of sevoflurane appeared in the literature in 1971. The agent was developed by  Ross Terrell, PhD. It was introduced into clinical practice initially in Japan in 1990. Its name comes from having seven fluorine atoms. The rights for sevoflurane in the US and other countries were held by Abbott Laboratories. It is now available as a generic drug.
Toxic breakdown products
Sevoflurane forms a range of degradation products, compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] also called PIFE (pentafluoroisopropenyl fluoromethyl ether) and Compound B [1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane], also called PMFE (pentafluoromethoxy isopropyl fluoromethyl ether) on contact with the soda lime in a rebreathing apparatus, which absorbs exhaled carbon dioxide, especially at higher temperatures and when the soda lime is desiccated. Compound A is formed by an elimination reaction which is likely to be the E2 reaction as for an E1 reaction a carbocation centred on a primary carbon bearing two fluorine atoms would have to form. Compound A reacts with methanol to form compound B by nucelophilic attack on the difluoroalkene group in compound A. A further elimination reaction forms compounds C, D and E. Hydrofluoric acid is formed in the same reaction as compound A, but as soda-lime is alkaline and contains calcium the hydrogen fluoride is likely to converted into insoluble calcium fluoride. Compound A has been shown to cause renal necrosis in rats.
Compound A reacts with the thiol groups in glutathione to form S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine which then undergoes an enzymic reaction to form ammonium ions, pyruvate and 2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropanethiolate. The 2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropanethiolate then is converted to an electrophile 2-(fluoromethoxy)- 3,3,3-trifluorothiopropanoyl fluoride which can react with the tissues causing damage.
In humans, direct histological evidence of renal toxicity has not been demonstrated, although there is dose-related proteinuria, glycosuria and enzymuria. During low-flow anaesthesia, when the lower fresh gas flow leads to decreased flushing of the circuit and increased temperature of the soda lime, compound A may build up to clinically significant levels, although there have never been any reports of adverse events in humans.
Sevoflurane also reacts with hydroxide anions to form fluoride anions and ((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)methanol, the ((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)methanol (Which is a hemi-acetal) breaks down to form formaldehyde and 1,1,1,3,3,3-hexafluoropropan-2-ol. The formaldehyde forms formic acid and methanol in a Cannizzaro reaction. The methanol then is used to form compound B.
As a result, sevoflurane is sometimes administered with a minimum fresh gas flow of 2 liters per minute, making it a relatively expensive choice for maintaining general anesthesia. Only two countries currently have recommended minimum flow rates of 2L/min; Canada and Australia. Recent generic competition in select markets has also significantly lowered the unit cost of sevoflurane, making it more cost effective.
Sevoflurane has been implicated in neuronal degeneration in infant mice. This activity is thought to occur via blockade of NMDA receptors or hyperactivity of GABA neurotransmission. In one study, the researchers showed exposure of infant mice to inhaled sevoflurane resulted in learning deficits and abnormal social behaviour.
|Boiling point:||58.6 °C||(at 101.325 kPa)|
|Density:||1.517–1.522 g/cm³||(at 20 °C)|
|MAC :||2.1 vol %|
|Molecular weight:||200 u|
|Vapor pressure:||157 mmHg (22.9 kPa)||(at 20 °C)|
|197 mmHg (26.3 kPa)||(at 25 °C)|
|317 mmHg (42.3 kPa)||(at 36 °C)|
|Blood:Gas partition coefficient:||0.68|
|Oil:Gas partition coefficient:||47|
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"Erratum". Drugs 52 (2): 253. August 1996.
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