title: Hepatocellular integrity in swine after prolonged desflurane (I-653) and isoflurane anesthesia: evaluation of plasma alanine aminotransferase activity.
abstract: Desflurane, formerly known as I-653 (CF2H-O-CFH-CF3), is a new inhalation anesthetic derived by fluorine substitution for the alpha-ethyl chlorine of isoflurane (CF2H-O-CClH-CF3). The lower solubility and increased stability of desflurane provided by the C-F bond lessen biotransformation to potentially hepatotoxic metabolites. Repeated administration of desflurane to rats, with or without induced hepatic enzymes, does not result in evidence of hepatic injury. In the recent study we extended the tests for liver cell injury to another species, the pig. Our test included prolonged exposure to desflurane or isoflurane, both in the absence and presence of commonly used adjuvants. We measured plasma alanine aminotransferase activity in eight young female swine anesthetized in random order with desflurane (0.8-1.6 MAC) and isoflurane (0.7-1.4 MAC), for a total dose of about 5.5 MAC-hours of each anesthetic, 3-8 days apart. Plasma alanine aminotransferase activities remained in the normal range, and were not significantly greater over baseline values in samples drawn immediately after, 4 h after, or 3-8 days after (mean +/- SD, 6.1 +/- 2.1) the administration of either anesthetic was discontinued after the first study with either desflurane or isoflurane. Five additional pigs were given a mean total dose of 9.7 MAC-hours of desflurane or isoflurane in conjunction with succinylcholine, N2O, fentanyl, naloxone, atracurium, thiopental, edrophonium, and atropine. No changes in plasma alanine aminotransferase activity were detected in blood samples drawn at termination of the anesthesia, 24 h later, and 4-7 days later (mean +/- SD, 5.8 +/- 1.3).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesia, University of California School of Medicine, San Francisco 94143-0648.
authors.forename: M A
authors.initials: MA
authors.lastname: Holmes
authors.forename: R B
authors.initials: RB
authors.lastname: Weiskopf
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: B H
authors.initials: BH
authors.lastname: Johnson
authors.forename: I J
authors.initials: IJ
authors.lastname: Rampil
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D000758:Anesthesia; D000777:Anesthetics / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000077335:Desflurane; D005260:Female; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D013552:Swine
chemical_list: D000777:Anesthetics; D000077335:Desflurane; D007530:Isoflurane; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase