SUBANESTHETIC HALOTHANE IS HEPATOTOXIC IN THE GUINEA-PIG

Subanesthetic concentrations of halothane were examined for their hepatotoxic potential in the guinea pig. Outbred male, Hartley guinea pigs (600-700 g) were exposed to either 1.0%, 0.25%, or 0.10% (vol/vol) halothane, 40% O2, for 4 h. Plasma isocitrate dehydrogenase (ICDH) activity was compared to plasma alanine aminotransferase (ALT) for sensitivity as an indicator of hepatic injury. As previously seen, exposure to the anesthetic concentration of 1.0% halothane produced limited to confluent centrilobular necrosis in 50% (4/8) of the guinea pigs. The subanesthetic concentrations of 0.25% and 0.1% halothane were also hepatotoxic. After exposure to 0.25%, confluent centrilobular necrosis developed in 2 of 8 animals, whereas 0.10% halothane produced limited centrilobular necrosis in 3 of 8. Plasma ICDH activity was a more sensitive indicator of halothane-induced hepatic injury than ALT. Mean plasma ALT activity increased significantly after 1.0% halothane exposure only. However, ICDH activity was significantly increased after exposure to all three concentrations of halothane. Comparison of peak plasma enzyme activities demonstrated significantly larger increases in ICDH than in ALT when centrilobular necrosis was present. Use of subanesthetic concentrations of halothane should help overcome the many transient effects that high concentrations of halothane have on whole liver and hepatocyte functions. By being able to isolate and titrate the bioactivation of halothane, the mechanisms through which halothane biotransformation produces acute hepatotoxicity should be more easily elucidated.