Halothane Hepatotoxicity: Relation Between Metabolic Activation, Hypoxia, Covalent Binding, Lipid Peroxidation and Liver Cell Damage
✍ Scribed by Herbert De Groot; Thomas Noll
- Book ID
- 102848288
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 601 KB
- Volume
- 3
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Although halothane (CF3CHBrCl) is a valuable and safe anesthetic agent not associated with mortality higher than with other anesthetics (l), a single exposure to halothane may be associated with severe hepatic necrosis in about 1 per 10,000 patients (1-3). The incidence increases after multiple exposures to halothane (1-4) and, in these cases, up to 20% manifest less severe forms of liver injury (2, 5, 6).
The usual clinical symptoms and signs of "halothane hepatitis" developing postoperatively are headache, anorexia, malaise, fever, jaundice, and lethargy, often with rapid development of hepatic precoma and coma (2, 7, 8). The liver is initially slightly enlarged, mildly tender, and firmer than normal (7, 8). The laboratory findings are characteristic of hepatocellular necrosis, including gross increases in SGOT and SGPT activities, hyperbilirubinemia, and depression of prothrombin activity (2, 7, 8). Morphologic changes are indistinguishable from those seen in patients who ingested carbon tetrachloride (2, 7, 8), are primarily confined to the centrolobular area, and include fatty metamorphosis, ballooning of cells, parenchymal cell necrosis, and cellular infiltration.
To date, the molecular mechanism of liver injury attributed to halothane hepatotoxicity is unknown. Although in some cases a hypersensitivity mechanism may be involved (9-13), experiments in laboratory animals (14-20) indicate that halothane acts as a direct hepatotoxin provided certain conditions are fulfilled. In this article, we will describe these conditions and, based on in uitro experiments, propose a molecular mechanism of halothane hepatotoxicity.
METABOLIC ACTIVATION Since the findings of van Dyke et al. ( 21) that halothane is neither inert nor nonmetabolized, a positive