Isoflurane

Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether; CAS 26675-46-7; molecular formula C3H2ClF5O; molecular weight 184.49) is a halogenated methyl ethyl ether volatile anesthetic introduced clinically by Ohio Medical Products in 1981. The minimum alveolar concentration (MAC) at 40 years of age is 1.15 percent in oxygen and 0.5 percent in 70 percent nitrous oxide. The blood-gas partition coefficient is 1.4, intermediate between halothane (2.4) and the modern agents desflurane (0.42) and sevoflurane (0.65); this corresponds to moderately fast induction and emergence relative to halothane but substantially slower than desflurane. Mechanism is multifactorial and incompletely characterized: principal targets include positive allosteric modulation of GABA-A receptors at sites distinct from benzodiazepine and barbiturate sites, two-pore domain potassium channel (TREK-1, TASK) activation, glycine receptor potentiation, and inhibition of NMDA glutamate currents at clinically relevant partial pressures. Cardiovascular effects include dose-dependent reduction in systemic vascular resistance and modest negative inotropy with preserved cardiac output through reflex tachycardia; coronary vasodilation has been studied for steal physiology but the clinical significance is limited. Respiratory effects include dose-dependent depression of tidal volume with compensatory tachypnea. Hepatotoxicity through trifluoroacetylated protein adduct formation occurs in 0.2 percent of metabolism (versus 20 percent for halothane) and the clinical incidence of immune-mediated hepatitis is correspondingly low. Used widely in veterinary anesthesia and in lower-resource settings where acquisition cost favors isoflurane over the newer agents.