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Halothane hepatitis

INTRODUCTION

Halothane was first introduced into use as an anesthetic in 1956, and replaced ether as the anesthetic of choice. Within two years, isolated case reports of severe hepatitis were being reported [1-3]. In 1969, the National Institutes of Health organized one of the largest epidemiological studies ever performed in the United States to evaluate halothane toxicity. A review of 250,000 cases of halothane use revealed an incidence of fatal hepatic necrosis of about 1 in 35,000 exposures [4]. A similar large-scale review in the United Kingdom showed nearly identical results [5]. Less toxic alternatives have been serially introduced: enflurane (1972), isoflurane (1981), desflurane (1992) and sevoflurane (1995), although reports of hepatoxicity with these medications also exist [6,7].

Concern about hepatotoxicity has virtually eliminated the use of halothane in adults in the United States. Initially, toxicity to halothane was not reported in children. However, subsequent reports demonstrated that the incidence of halothane-associated hepatitis in children is between 1 in 82,000 and 1 in 200,000 [8-13]. Because it is highly potent and has a tolerable odor, halothane continues to be used for the induction of anesthesia in children in the United States. The reason for the lower incidence of halothane-associated hepatitis observed in children is unclear [14,15]. Furthermore, halothane is possibly the most commonly used inhalational anesthetic in all patients worldwide [16] and reports of hepatotoxicity continue to be published [17-19].

CLINICAL FEATURES

Halothane is associated with two clinical patterns of hepatotoxicity (sometimes classified as type 1 and 2) [19-22]:

  • Type 1 — Serum aminotransferase elevation either without symptoms or with mild, self-limited symptoms; and
  • Type 2 — Severe hepatitis or acute liver failure.

Halothane is commonly associated with asymptomatic elevation in serum aminotransferases [4,5,20,23,24]. Approximately 20 to 25 percent of these patients develop symptoms of mild clinical hepatitis characterized by nausea, lethargy, and fever. The aminotransferases remain elevated for one to two weeks following exposure, and resolve without treatment. Eosinophilia may also be present. An acute hepatitis-like injury is seen on hepatic histology.
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