Sevoflurane

Sevoflurane (fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether; CAS 28523-86-6; molecular formula C4H3F7O; molecular weight 200.05) is a fluorinated methyl isopropyl ether volatile anesthetic synthesized by Ross Terrell at Travenol Laboratories in 1968, brought to clinical use in Japan in 1990, and approved by the FDA in 1995 (Ultane, Sojourn). The minimum alveolar concentration (MAC) at age 40 is 1.8 percent in oxygen; the blood-gas partition coefficient is 0.65, faster than isoflurane (1.4) but slower than desflurane (0.42). The non-pungent character and absence of airway irritation make sevoflurane the agent of choice for inhalational induction of anesthesia, particularly in pediatric patients where intravenous access is established after induction. Mechanism parallels other halogenated ethers (GABA-A positive allosteric modulation, K2P channel activation, glycine and NMDA effects); the agent is achiral. Hepatic metabolism via CYP2E1 produces hexafluoroisopropanol and inorganic fluoride; the fluoride concentrations approach the historical nephrotoxic threshold associated with methoxyflurane (50 micromolar plasma) during prolonged exposure but published clinical data have not demonstrated nephrotoxicity in humans even with extended cases, attributed to the absence of intrarenal defluorination. The principal residual concern is degradation of sevoflurane in carbon dioxide absorbents (soda lime, Baralyme) at low fresh gas flows producing Compound A, which is nephrotoxic in rats but lacks demonstrated human renal injury within recommended fresh gas flow limits (1 to 2 L/min). Cardiovascular profile is favorable with preserved cardiac output, modest reduction in systemic vascular resistance, and minimal coronary steal physiology.