Biotransformation in man and clinical toxicity of volatile anesthetics.

Delayed toxic reactions following general anesthesia are dependent on biotransformation of ansethetic drugs. Up to ten grams of metabolites of the more extensively metabolized volatile anesthetics may undergo irreversible intracellular binding. This could contribute importantly to the incidence of hepatic necrosis. A second important cause of toxic reactions is production of toxic metabolites. Nephrotoxicity with impairment of urine concentrating ability following methhoxyflurane anesthesia correlates best with blood fluoride levels and total urinary oxalate. A possible role of enzyme induction in hepatic and hepatorenal failure following, fluroxene anesthesia is suggested by recent studies in the monkey, which demonstrate that pretreatment with phenobarbital results in increased production of a toxic metabolite and conversion of a well tolerated anesthesia to a rapidly lethal one. Improvement in the safety to general anesthesia can be expected from either of two developments: production of anesthetics which are resistant to biotransformation, or development of drugs which will inhibit biotrasnformation during and immediately following anesthesia when maximum rates of biotransformation tend to occur. An important additional safeguard will have been achieved when a successful method is found to identify before exposure patients who may susceptible to delayed toxic reactions.