Metabolism of the inhaled anaesthetics: implications of enzyme induction.

Treatment with drugs and exposure to many environmental chemicals results in enzyme induction. However, the clinical significance of increased (or altered) metabolism of the inhaled anaesthetics appears to be trivial. Enzyme induction does not affect the conduct of inhalation anaesthesia. Thus, only delayed organ toxicity is at issue. Since methoxyflurane has fallen into disuse, nephrotoxicity secondary to its administration is no longer a problem. Nephrotoxicity as a result of enhanced defluorination of enflurane or isoflurane is also unlikely: enflurane biotransformation, in most circumstances, is uninducible; isoflurane is metabolized to such a small extent that any increase in its metabolism would be clinically inconsequential. Whether induction of halothane biotransformation and the production of reactive intermediates may lead to hepatoxicity is not yet settled. It is quite clear that induction, in the presence of hypoxia, leads to hepatic necrosis in rats. However, a similar relationship has not been established in surgical patients.