Sevoflurane: a new inhalational anesthetic agent

Abstract

Laboratory screening of a series of halogenated methyl isopropyl ethers revealed sevoflurane (fluoromethyl-1,1,1,3,3,3,-hexafluroro-2-propyl ether) as a potent nonexplosive inhalational anesthetic agent. Sevoflurance, a pleasant-smelling liquid, boils at 58.5 degrees C at 760 torr and has a vapor pressure of 200 torr at 25 degrees C. It is nonflammable in air and has lower flammability limits of 11 vols percent in O2 and 10 vols percent in N2O. Sevoflurane exhibits limited chemical reactivity in vitro; it is subject to slight but measurable hydrolysis, and reacts with soda lime to form traces of related ethers. It provides rapid anesthetic induction and recovery consistent with its low distribution coefficients (blood:gas, 0.6; corn oil:gas, 41.6; olive oil:gas, 53.4). In dogs, anesthetic concentrations of sevoflurane did not produce spontaneous cardiac arrhythmias and did not sensitize the heart to epinephrine. Electroencephalographic patterns were similar to those observed during anesthesia with halothane. In rats, small increases in the urinary excretion of inorganic fluoride ion occurred during the first 24 hours after anesthesia. Subacute studies in dogs and rats, using closed-circle absorption with soda lime, revealed no toxicologically significant changes in animals anesthetized frequently for 2 weeks. Sevoflurane appears to be a unique volatile anesthetic agent worthy of further study.