Hypoxia may be more important than reductive metabolism in halothane-induced hepatic injury

To evaluate the relative importance of halothane metabolism and liver hypoxia in the occurrence of hepatic injury, the injury produced in hypoxic rats exposed to identical MAC hours of halothane but at various concentrations of halothane was compared. Groups of male Sprague-Dawley rats were pretreated with phenobarbital for 4 days, and 24 hours later they were exposed to 10 hours of 10% oxygen and concomitantly 0.2 MAC hours of halothane at the following anesthetic concentrations: 0.02% for 10 hours, 0.1% for 2 hours, 0.5% for 24 minutes, or 2.5% for 4.8 minutes. A control group received only 10% oxygen for 10 hours. Liver specimens taken 24 hours later demonstrated concentration-dependent damage; high concentrations given briefly produced more damage than lower concentrations given for long periods. As hepatic clearance of halothane by metabolism appears to be a saturable phenomenon, these results suggest that hypoxia per se may be more important than halothane metabolism in causing liver damage.