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Anesth Analg 1988; 67:448-452
© 1988 International Anesthesia Research Society
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Halothane Hepatotoxicity and Reductive Metabolism of Halothane in Acute Experimental Liver Injury in Rats

Fumio Nomura, MD, Hitoshi Hatano, MD, Shinji Iida, MD, and Kunihiko Ohnishi, MD

The Department of Medicine, Chiba University School of Medicine, Chiba, Japan.

Abstract

Reductive metabolism of halothane was measured after acute liver injury induced by galactosamine (1.0 g/kg, IP) in rats. On the seventh day of liver injury, when previously elevated scrum alanine aminotransferase levels had returned to near normal range, anaerobic release of fluoride from halothane by hepatic microsomes, which appears to reflect the reductive pathway of halothane metabolism, was still remarkably decreased (1.36 ± 0.56 nmol/mg protein/h vs 5.88 ± 0.58 in controls, P < 0.001). In another set of experiments, rats (n = 8) given galactosamine 7 days earlier and saline-treated control rats were given halothane anesthesia (1.0%) under mildly hypoxic conditions (FIO2, 0.14). In saline controls, halothane anesthesia resulted in a mild but statistically significant increase in serum alanine aminotransferase levels (32 ± 4 vs 59 ± 6 U/ml, P < 0.001). In contrast, serum levels of this enzyme were not changed by halothane anesthesia in galactosarnine-treated rats (45 ± 3 z>s 49 ± 4 U/ml). Although care should be taken in extrapolating the importance of these animal data to humans, the results of this study suggest that halothane hepatotoxicity can be attenuated in the presence of minor liver injury as a result of decreased hepatic bio trans formation of the anesthetic. The data support the view that halothane anesthesia is not necessarily contraindicated in subjects with impaired liver function.

Key Words: ANESTHETICS, VOLATILE—halothane. • LIVER—hepatic toxicity. • TOXICITY—halothane.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1988 by the International Anesthesia Research Society.