METHODOLOGY OF A PROSPECTIVE STUDY OF CHANGES IN LIVER ENZYME CONCENTRATIONS FOLLOWING REPEAT ANAESTHETICS

The methodology of a large prospective study on the influence of repeated anaesthetics on liver function is reported and the problems involved are discussed. The most suitable patients were those presenting for endoscopic examination of the bladder and urethra, for urethral dilatation and for cervical implantation of radium. Blood samples were taken immediately before induction of anaes-thesia and on days 3-4 and 13-15 after operation, when a clinical assessment of the patient was also carried out. The concentrations of six enzymes (lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, serum cholinesterase and gamma glutamyl transpeptidase) were chosen specifically as indices of liver function. The eosinophil count was measured to reflect any hypersensitivity reaction. The non-Gaussian distribution of thesenecessitated using appropriate non-parametric tests together with parametric tests on logarithmic transformed data. In addition a quantal method was used to measure the frequency of patients showing an "abnormal " increase in enzyme concentrations. Unexplained hepatitis in some patients following halothane anaesthesia resulted in the setting up of the National Halothane Study in the United States in 1963. This retrospective survey of more than 850 000 anaesthetics implicated halothane as a cause of massive hepatic necrosis in less than 1 in 10 000 administrations (Bunker et al., 1969). Subsequently, various workers (Muslim, Rosen and Jones, 1971; Sharpstone, Medley and Williams, 1971; Inman and Mushin, 1974) incriminated repeated exposure to halothane and reported that there was an increase in the likelihood of liver dysfunction as the interval between successive halothane anaesthetics decreased. "Halothane hepatitis " is characterized by the appearance of fever up to 2 weeks after anaesthesia, followed by symptoms resembling viral hepatitis. Often eosinophilia is found, which is in keeping with the view that the liver damage may be the result of a delayed hypersensitivity response to halothane or on