Halothane-Induced Liver Injury as a Consequence of Enhanced Microsomal Lipid Peroxidation in Guinea Pigs

Abstract

Comment The issue of hepatotoxicity produced by halothane (and other halogenated anesthetics) is just as unsettled as it has been for years. A casual observer of the controversy is overwhelmed by changing concepts, advances and retreats, and nonextrapolatable animal data. In the early 1960 era, “halothane hepatitis” was ascribed to an allergy, peculiar to humans since liver damage could not be produced in animals. By the early 1970 era, with the new realization that halothane is biotransformed, a metabolic cause ascribed to reactive intermediates via a non-oxygen dependent or reductive pathway was proposed. Opponents to this thesis argued that all liver damage following anesthesia is due to hy-poxia caused by critical alterations in hepatic blood flow. Lately the popular line describes ha-lothane toxicity as due to an initial biotransfor-mation to an oxidative metabolite (trifluoroacetic acid) which covalently binds to contiguous liver proteins to form an haptene, which in turn produces an immunologic hepatic response. The guinea pig model has been employed recently to avoid the hypoxia associated with the rat-phenobarbital induction-low FIO2 model. A debate now rages as to whether histologic damage produced in this model is metabolic or immunologic. The present paper from the University of Hiroshima in Japan would ascribe it to a metabolic phenomenon since lipid peroxides are products of free radical formation. Is this applicable to humans? This editor does not know; neither do the authors of the article. Nonspecific changes due to hypoxia have been ruled out nicely by this group since equivalent concentrations of isoflu-rane and enflurane caused neither hepatic histologic changes nor enhanced lipoperoxidation. Burnell R. Brown, Jr., M.D., Ph.D., F.F.A.R.C.S.