Sevoflurane

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 most volatile anesthetic with the fastest onset and offset. Though desflurane has the lowest blood/gas coefficient of the currently used volatile anesthetics, it 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 scientists at Baxter Laboratories. 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 are held by Abbott Laboratories.

Anesthesia gases used globally contribute the equivalent of 1 million cars to global warming. Sevoflurane is a greenhouse gas, with a global warming potential of 345. One tonne of sevoflurane emitted is equivalent to 345 tonnes of carbon dioxide in the atmosphere. However, the global warming potential of sevoflurane is lower than that of either isoflurane or desflurane, even considering the different amounts typically used in 1 hour of anesthesia (1 minimal alveolar concentration-hour). For this reason, barring other clinical reasons, sevoflurane should be preferred for its relatively lower environmental impact.

Sevoflurane forms at least two 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. Hydrofluoric acid is formed in the same reaction as compound A. Compound A has been shown to cause renal necrosis in rats. 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. 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 maintain mandatory 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, the researchers showed exposure of infant mice to inhaled sevoflurane resulted in learning deficits and abnormal social behaviour

Sevoflurane raises the intracranial tension and can cause respiratory depression.

Global-warming potential
The twenty-year global-warming potential, GWP(20), for sevoflurane is 349.

Additional reading
Wallin, Richard F., Regan, Bernard M., Napoli, Martha D., Stern, Ivan j. (Nov.-Dec. 1975). "Sevoflurane: A New Inhalational Anesthetic Agent". Anesthesia and Analgesia, 84(6), 58-766.