Metabolism of halothane in obese Fischer 344 rats.
Halothane is metabolized by an oxidative pathway to stable, nonvolatile end products, trifluoroacetic acid (TFAA) and bromide (Br-), and by reductive pathways to Br-and inorganic fluoride (F-). There is evidence that both oxidatively and reductively formed intermediates may produce hepatotoxicity, although the exact etiology of the fulminant hepatic necrosis seen in humans is unproven. Obese patients receiving volatile anesthetics exhibit higher serum anesthetic metabolite concentrations than do normal-weight patients, and thus might be at greater risk of hepatotoxicity because of higher concentrations of reactive intermediates from halothane metabolism. To eliminate the variables inherent in human clinical studies leading to confounding interpretation of data, this study determined the contributions of oxidative and reductive pathways to halothane metabolism in an animal model of human hypertrophic obesity, the most common form of human obesity. Eight pairs of obese (high-fat diet) and normal-weight (standard chow), male Fischer 344 rats were anesthetized with halothane for 4 h at an inspired concentration of 0.78%. Serum and urinary concentrations of TFAA, Br-, and F-were measured. Thirty-six hours following halothane anesthesia, mean serum TFAA concentrations peaked at 7.3 +/- 1.1 mM in obese rats and 4.7 +/- 0.7 mM in nonobese rats. TFAA urinary excretions during the 180-h period postanesthesia were 519 +/- 69 and 336 +/- 22 mumol, respectively. Peak serum Br- concentrations were 9.1 +/- 1.0 and 6.9 +/- 0.6 mM for obese and nonobese rats, respectively, and Br-urinary excretions were 127 +/- 30 and 79 +/- 14 mumol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesia, Stanford University School of Medicine, California.
J S
JS
Biermann
S A
SA
Rice
K J
KJ
Fish
M T
MT
Serra
D000818:Animals; D001965:Bromides / Q000032:analysis / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005459:Fluorides / Q000032:analysis / Q000378:metabolism; D006221:Halothane / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344 / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D013997:Time Factors; D014269:Trifluoroacetic Acid / Q000032:analysis / Q000378:metabolism
D001965:Bromides; D004041:Dietary Fats; D014269:Trifluoroacetic Acid; D005459:Fluorides; D006221:Halothane