Anesthetic hepatotoxicity was tested under various conditions of hypoxia in rats pretreated with phenobarbital. Administration of 0.3 MAC halothane or fentanyl in 9% oxygen (fractional concentration of inspired oxygen = 0.09) for 46 min produced centrilobular hepatic injury in all rats (P less than 0.001 vs all other groups). Isoflurane, nitrous oxide, and thiopental at 0.3 MAC did not produce hepatic injury greater than that produced in control rats given 9% oxygen, nor was significant injury produced in control phenobarbital-pretreated rats who breathed 6 or 7.5% oxygen for 46 min. With an inspired oxygen concentration of 7.5%, hepatic injury occurred after exposure to 92.5% nitrous oxide (P less than 0.05), but not after enflurane, isoflurane, or thiopental. When hypoxia associated with 9% oxygen was extended to 2 hr, 91% nitrous oxide produced significant injury (P less than 0.001 compared with the controls), while enflurane, isoflurane, and thiopental did not. These and previous results suggest that all anesthetics can produce liver injury in the hypoxic rat model and that the ranking of hepatotoxicity (most to least) may be halothane, fentanyl, nitrous oxide, enflurane = isoflurane = thiopental.
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