Hepatorenal toxicity following fluroxene anesthesia

Abstract

A 47 yr old women died after a fluroxene anesthesia. At autopsy, morphological changes in liver and kidney were found. The role of the patient's exposure to sedatives and other drugs is subject only to speculation, but suggests that induction of microsomal enzymes may have occurred prior to floroxene exposure. Fluroxene is metabolized largely to trifluoroethanol TFE in experimental animals, a lesser fraction appearing in the urine as trifluoroacetic acid TFAA. TFAA is the principal metabolite in man, and less than 1% normally occurs as TFE. It is possible that enzyme induction may influence the occurrence of a toxic metabolite. The toxicity of TFE is seven to 12 times greater than that of TFAA, and accounts for the observation that fluroxene is consistently toxic to mice, dogs, cats, and rabbits. It is also possible that conditions favoring one metabolic pathway over another, or an unusual production of TFE or some other metabolite, were responsible for the hepatic necrosis in this patient. The presence of concomitant renal failure may also have enhanced toxicity by decreasing the clearance of fluroxene metabolites. Although a search for metabolites shortly before death (fifth day) failed to reveal evidence of excessive quantities of TFE or other organic fluorine compounds, it does not eliminate the possibility that these compounds were present in higher concentration on the first several days following anesthesia.