Halothane and liver damage.

The Medical Assessor to the Committee on Safety ofMedicines recently issued' a letter entitled "Jaundice following repeated exposure to halothane," in which he noted that 130 reports of jaundice following anaesthesia had been received by the committee between 1964 and 1972, every case being associated with the use of halothane. Ninety-four of these patients had been exposed to halothane more than once. The assessor referred to the paper2 by Inman and Mushin which analysed these reports, and he accepted as established that multiple exposure to halothane carries a greater risk of jaundice than a single exposure, with the suggestion that repeated exposure within a few weeks may carry a greater risk, though no particular time interval was necessarily critical. This "additional evidence" was accepted by him and the letter circulated so that anaesthetists could be better able to assess all the relative risks ofvarious agents in the clinical circumstances ofeach case. The results of the assessor's letter have perhaps not been quite up to his expectations. Far from enabling anaesthetists to put the risk of liver damage into perspective, the new information has had at least two unfortunate effects. It has thrown open the question of negligence if an anaesthetist is faced with the occurrence of postoperative jaundice when he has given the patient more than one halothane anaesthetic within four weeks. It has led local ethical committees to forbid clinical trials designed to investigate the role of halothane in postoperative jaundice; in one centre such a trial was terminated. The time has, therefore, come to look impartially at the available evidence to try to distinguish fact from hypothesis and opinion. Despite numerous scientifically valid experiments on animals in which no direct liver toxicity was shown, halothane has been under suspicion as a hepatotoxic agent since its introduction, simply because it is a volatile halogenated hydrocarbon metabolized by the liver. The term "halothane hepatitis" has commonly been used without adequate diagnostic criteria for the condition, and indeed this label has been applied in all cases by the process of exclusion of other recognized causes. Sporadic cases of jaundice, death from hepatic necrosis, and hepatorenal syndrome have been reported for more than 50 years, and almost no anaesthetic agent, local or general, has been excluded from blame. The National Halothane Study3 retrospectively examined 856,515 general anaesthetics which had been given over a four-year period and reported a critical