Evidence for acute cellular changes in human hepatocytes during anesthesia with halogenated agents: an electron...

Liver biopsy specimens of 24 patients who had elective laparotomies were studied by electron microscopy for evidence of anesthesia-related toxic changes. All patients were initially anesthetized with nitrous oxide, barbiturate, and narcotic until the laparotomy incision was completed and an initial preanesthesia liver biopsy specimen was taken. Patients were then give, in randomized fashion, maintenance inhalational anesthesia for the duration of the procedure with halothane, fluroxene, or enflurane. Control patients were continued on nitrous oxide, barbiturate, and narcotic. After approximately 60 minutes a second postanesthesia liver biopsy specimen was taken. For each patient, the preanethesia and postanesthesia liver biopsy specimens were compared, in blinded fashion, for evidence of morphologic changes resulting from anesthesia. Ultrastructural changes consistent with hepatic toxicity were present in more than 25% of the cells examined in the postanesthesia specimens in all of the seven patients given halothane, five of the six patients given fluroxene, and one of the five patients given enflurane. None of the six nitrous oxide-barbiturate-narcotic control patients showed toxic changes in postanesthesia specimens. The most prominent toxic change was dilatation of endoplasmic reticulum. Accumulation of intracellular inclusions occurred in some cells, and a small percentage of cells also showed lipid accumulation and mitochondrial swelling. Evidence suggested that exposure to halogenated anesthetics is related to acute toxic subcellular changes in hepatocytes.