Halothane, anesthesia with, associated hepatic

National Halothane Study/NRC Report (1966) Summary of the national halothane study. Possible association between halothane anesthesia and postoperative hepatic necrosis. Report on the national halothane study of the Committee on Anesthesia, National Academy of Sciences - National Research Council. JAMA 197 775-788 Paronetto F, Popper H (1970) Lymphocyte stimulation induced by halothane in patients with hepatitis following exposure to halothane. N Engl J Med 283 277-280 Paton WDM (1957) Histamine release by compounds of simple chemical structure. Pharmacol Rev 9 269-328... 

Hepatic damage related to isoflurane anesthesia has very occasionally been described (9,10), including one report of hepatic necrosis and death (11). Hepatitis or hepatocellular injury has been described with all current volatile anesthetics. Among these, halothane-associated hepatitis has been best characterized and is probably caused by an immune reaction induced by hepatocyte proteins that have been covalently trifluoroacetylated by the trifluoro-acetyl metabolite of halothane. The reactive acyl-halide metabolite of trifluoroacetic acid can trifluoroacetylate liver proteins, resulting in immune-mediated hepatic necrosis (12). However, isoflurane biotransformation to trifluoroacetate is less than 0.2%, compared with 15-20% for halothane. 

Minor alterations in hepatic dysfunction also occur more commonly after halothane administration than other general anesthetics now in common use (Wright et al. 1975). Nonetheless, when jaundice occurs after halothane use, the prognosis is serious. In a review by Little in 1968 the mortality rate was calculated to be 35% in the 400 patients who had developed this complication. When death occurs, it is usually due to hepatic failure with coma. Obesity, early onset of jaundice after anesthesia, and associated blood coagulation abnormalities are more likely to be associated with a fatal outcome. If recovery occurs, it is almost always complete. In... 

Peters RL, Edmondson HA, Reynolds TB, Meister JC, Curphey TJ (1969) Hepatic necrosis associated with halothane anesthesia. Am J Med 47 748-764 Phillips GH (1974) Structure-activity relationship in steroidal anaesthetics. In Halsy MJ, Millar RA, Sutton JA (eds) Molecular mechanisms in general anaesthesia. Churchill-Livingstone, Edinburgh London, pp 32-46... 

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