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PEDIATRIC ANESTHESIA

Autoantibodies Associated with Volatile Anesthetic Hepatitis Found in the Sera of a Large Cohort of Pediatric Anesthesiologists

Dolores B. Njoku, MD^*, Robert S. Greenberg, MD^*, Mohammed Bourdi, PhD, Craig B. Borkowf, PhD, Elizabeth M. Dake, MS^*, Jackie L. Martin, MD^*, and Lance R. Pohl, Pharm D, PhD

Departments of *Anesthesiology and Critical Care Medicine and Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland, the Molecular and Cellular Toxicology Section of the Laboratory of Molecular Immunology, and the Division of Epidemiology and Clinical Applications, Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

Address correspondence and reprint requests to Dolores B. Njoku, MD, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Hospital, Blalock 906A, 600 N Wolfe St., Baltimore, MD 21287. Address e-mail to dnjoku{at}jhmi.edu

Anesthetic-induced hepatitis is thought to have an immune-mediated basis, in part because many patients who develop hepatitis have serum autoantibodies that react with specific hepatic proteins. The present study shows that pediatric anesthesiologists also have these serum autoantibodies. Moreover, levels of these autoantibodies are higher than those of general anesthesiologists. We collected sera from 105 pediatric and 53 general anesthesiologists (including 3 nurse anesthetists), 20 halothane hepatitis patients, and 20 control individuals who were never exposed to inhaled anesthetics. Serum cytochrome P450 2E1 (P450 2E1) and 58-kd hepatic endoplasmic reticulum protein (ERp58) autoantibodies were measured by enzyme-linked immunosorbent assays. Positive values were 2 SD above median control values. Two multiple regression models were constructed. Pediatric anesthesiologists, like halothane hepatitis patients, had higher serum autoantibody levels of ERp58 and P450 2E1 than general anesthesiologists and controls, which was possibly because of their increased occupational exposures to anesthetics. Female anesthesiologists had higher levels of ERp58 autoantibodies than male anesthesiologists, whereas female pediatric anesthesiologists had higher levels of P450 2E1 autoantibodies than all other anesthesiologists. One female pediatric anesthesiologist had symptoms of hepatic injury. Because most anesthesiologists do not develop volatile anesthetic-induced hepatic injury, the findings suggest that pathogenic ERp58 and P450 2E1 autoantibodies may not directly cause volatile anesthetic hepatitis. Female anesthesiologists have high levels of these autoantibodies; however, the majority of these individuals do not develop hepatitis, suggesting that autoantibodies may not have a pathological role in volatile anesthetic-induced hepatitis.

IMPLICATIONS: Environmental exposure of anesthesiology personnel to certain inhaled anesthetics can induce the formation of autoantibodies that have been associated with anesthetic hepatitis. Female anesthesiologists have high levels of these autoantibodies; however, the majority of these individuals do not develop hepatitis, suggesting that autoantibodies may not have a pathological role in volatile anesthetic-induced hepatitis.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999