Metabolism and toxicity of the new anesthetic agents.
Human biotransformation of the newer anesthetics, desflurane and sevoflurane, has been characterized in vitro and in vivo. Major metabolites of desflurane are inorganic fluoride and trifluoroacyl chloride, which may bind to tissue proteins or form trifluoroacetic acid, which is excreted in urine. Major metabolites of sevoflurane are fluoride and hexafluoroisopropanolol (HFIP), which is rapidly glucuronidated and excreted as HFIP-glucuronide in urine. The rate of sevoflurane metabolism is approximately one-third that of methoxyflurane, and 1.5-2 times that of enflurane, while that of desflurane is minimal. The extent of metabolism of sevoflurane and desflurane is 2-5% and 0.02-0.2% of the dose taken up, respectively. Peak serum fluoride concentrations occur within one hour after sevoflurane anesthesia, are usually in the range of 20-40 microM, and decline rapidly. Fluoride concentrations have exceeded 50 microM in approximately 7% of sevoflurane patients. For sevoflurane, the plasma fluoride concentration-time profile most closely resembles that of enflurane. For desflurane, elevations of plasma metabolite concentrations can only be detected after prolonged anesthesia. Investigations to date suggest that the biotransformation of sevoflurane does not appear to result in clinically significant hepatotoxicity or nephrotoxicity. Only a single case of immune-mediated desflurane hepatotoxicity has been reported.
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