Halothane jaundice

The first well-documented case (Klatskin and Kimberg 1969) was that of an anaesthetist who developed hepatitis seven times in 5 years. Each of these attacks followed his return to work and re-exposure to halothane. Jaundice was preceded by systemic manifestations which could all be explained by, or interpreted as, manifestations of an immunologically mediated reaction. These included pyrexia, myalgia and eosinophilia. Serial liver biopsies which were carried out showed hepatic cell necrosis, followed by the development of post-necrotic cirrhosis. It had to be established whether that patient was sensitive to halothane, because of the nature of his occupation. Thus, he was exposed to subanaesthetic doses of that agent. 

The answer is d. (Hardman, pp 308-313.) Halothane is a substituted alkane general anesthetic. It undergoes significant metabolism in humans with about 20% of the absorbed dose recovered as metabolites. Halothane can cause postoperative jaundice and hepatic necrosis with repeated administration in rare instances. 

About 20% of halothane is metabolised and it induces hepatic enzymes, including those of anaesthetists and operating theatre staff. Hepatic damage occurs in a small proportion of exposed patients. Typically fever develops 2 or 3 days after anaesthesia accompanied by anorexia, nausea and vomiting. In more severe cases this is followed by transient jaundice or, very rarely, fatal hepatic necrosis. Severe hepatitis is a complication of repeatedly administered halothane anaesthesia and has an incidence of 1 50000. It follows immime sensitisation to an oxidative metabolite of halothane in susceptible individuals. This serious complication, along with the other disadvantages of halothane and the popularity of sevoflurane for inhalational induction, has almost eliminated its use in the developed world. It remains in common use other parts of the world because it is comparatively inexpensive. 

In addition, biliary obstructive jaundice can also be caused by drug-induced toxicity, e.g. with Ciy-substi-tuted steroids, erythromycin estolate, chlorpromazine, chlorpropamide, ajmaline, halothane, methylthiouracil. 

The importance of multiple anesthetics should not be overlooked. For example, patients in whom halothane anesthesia is given twice, at an interval of less than 6 weeks, are at major risk of developing jaundice. Some anesthetists avoid any second exposure to this agent. However, there are several reasons why single agents are often insufficient in anesthesia different problems require separate treatments the severity of the adverse effects of indi-vidual drugs can sometimes be reduced by... 

A 6-year-old boy sustained pelvic injuries and a femoral fracture. The first anesthetic he received consisted of thiopental, suxamethonium, isoflurane, and nitrous oxide. He also received two units of blood. He subsequently underwent four halothane anesthetics over 6 weeks for dilatation of a urethral stricture. Two days after the last anesthetic he was noted to be jaundiced. He had a negative viral screen but was positive for antitrifluoroacetyl IgG antibodies. He developed fulminant hepatic failure with grade 2 hepatic encephalopathy and underwent an auxiliary Uver transplantation 24 days after his last exposure to halothane. He died of septicemia 18 days later. Both at autopsy and on a previous hepatobiliary scan he was noted to have had extensive native Uver regeneration. 

An obese 35-year-old diabetic woman developed isoflurane-induced hepatotoxicity (15). She had had four previous halothane anesthetics, the last two of which were associated with jaundice. She made a full recovery and during a subsequent anesthetic received an infusion of propofol. Unfortunately, trifluoroacetic acid antibody titers were not performed. Liver function does not appear to have been severely affected peak alanine transaminase activity was 1410 IU/1. 

Jaundice after general anesthesia in which nitrous oxide was the only anesthetic has been described (36). However, contamination with halothane was not definitely ruled out. 

Hart SM, Fitzgerald PG. Unexplained jaundice following non-halothane anaesthesia. A case report. Br J Anaesth 1975 47(12) 1321-6. 

In contrast, type II hepatotoxicity is associated with massive centrilobular liver cell necrosis that can lead to fulminant liver failure. Type II hepatotoxicity is characterized by fever, jaundice, and very high serum transaminase levels. It may be immune-medi-ated and is thought to occur in genetically predisposed individuals. The incidence of type II hepatotoxicity 1 35 000 with one exposure to halothane and... 

Halothane Hepatitic Generally less than twice the upper reference limit in patients who develop jaundice (W6)... 

Njoku D, Easter MJ, Gong DH, Eger El, Reed GF, Martin JL (1997) Biotransframation of halothane, enflurane, isofiurane, and desfiurane to trifiuoroacetylated liver proteins association between protein acylation and hepatic injury. Anesth Anaig 84 173-178 O Donohue J, Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, Mills PR (2000) Co-amoxiclav jaundice clinical and histological features and HLA class II association. Gut 47 717-720... 

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... 

Several other cases of hepatitis resulting from occupational exposure to halo-thane have been reported. Thus, there is little doubt that hepatitis may follow the inhalation of this anaesthetic. Extensive surveys of post-operative jaundice have also been carried out. A summary of the findings will be given here. Despite numerous reports in the literature of liver damage in patients who had halothane anaesthesia, there is still considerable controversy between anaesthetists and pathologists as to whether the hepatitis and halothane are causally related. 

According to a number of surveys of post-operative jaundice, the majority of patients who developed jaundice after halothane administration had received that agent more than once within a short period (a few weeks). 

In view of the difficulty in diagnosis, the actual incidence of halothane hepatitis is hard to assess (National Halothane Study 1966 Simpson et al. 1971 Dykes et al. 1972 Inman and Mushin 1974 Inman 1978). Other causes of post-operative pyrexia and jaundice are difficult to rule out.. Furthermore, these other causes may contribute or predispose to halothane hepatitis (Editorial 1980). The survey by Peters et al. (1969) suggests that the incidence of halothane hepatitis is 0.7 in 1,000. Fatal reactions are reported to be between 1 in 6,000 and 1 in 22,000. 

A case of jaundice after a general anaesthesia in which nitrous oxide was the only anaesthetic has recently been described (16C), but the possibility of contamination with halothane retained in the anaesthetic machine (9C) could not be excluded. 

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