ABSTRACT
Liver dysfunction may occur in patients exposed to any of the current generation of volatile
anesthetic agents. These drugs are halogenated compounds that undergo metabolism in the
liver by cytochromes P450 (CYP, particularly CYP2E1), generating chemically reactive inter-
mediates that interact with cellular macromolecules. However, the liver damage that occurs
in man following exposure to volatile anesthetics is not attributable to “conventional” cell
cytotoxicity initiated within the liver by reactive intermediates (as has been described for many
other halogenated compounds, e.g., the anesthetic chloroform) (1,2). Rather, in susceptible
patients, covalent binding of reactive metabolites to liver proteins triggers specific adaptive
immune responses that are believed to mediate the hepatotoxicity. This process was first
described for halothane, and similar mechanisms have been proposed to explain liver injury
caused by enflurane, isoflurane, and desflurane. Analogous mechanisms have also been
proposed to explain cases of liver damage in humans exposed accidentally to high levels of
halogenated hydrocarbon refrigerants, which are related chemically to the volatile anesthetics
and undergo CYP-mediated metabolic bioactivation in the liver.
