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Original Article
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Volume 340:832-838 March 18, 1999 Number 11
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Fomepizole for the Treatment of Ethylene Glycol Poisoning
Jeffrey Brent, M.D., Ph.D., Kenneth McMartin, Ph.D., Scott Phillips, M.D., Keith K. Burkhart, M.D., J. Ward Donovan, M.D., Melanie Wells, M.D., Ken Kulig, M.D., for The Methylpyrazole for Toxic Alcohols Study Group

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ABSTRACT

Background Ethylene glycol poisoning causes metabolic acidosis and renal failure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of ethylene glycol poisoning.

Methods We administered intravenous fomepizole to 19 patients with ethylene glycol poisoning (plasma ethylene glycol concentration, >=20 mg per deciliter [3.2 mmol per liter]). Patients who met specific criteria also underwent hemodialysis. Treatment was continued until plasma ethylene glycol concentrations were less than 20 mg per deciliter. Acid–base status, renal function, the kinetics of fomepizole, and ethylene glycol metabolism were assessed at predetermined intervals.

Results Fifteen of the patients initially had acidosis (mean serum bicarbonate concentration, 12.9 mmol per liter). Acid–base status tended to normalize within hours after the initiation of treatment with fomepizole. One patient with extreme acidosis died. In nine patients, renal function decreased during therapy; at enrollment, all nine had high serum creatinine concentrations and markedly elevated plasma glycolate concentrations (>=97.7 mg per deciliter [12.9 mmol per liter]). None of the 10 patients with normal serum creatinine concentrations at enrollment had renal injury during treatment; all 10 had plasma glycolate concentrations at or below 76.8 mg per deciliter (10.1 mmol per liter). Renal injury was independent of the initial plasma ethylene glycol concentration. The plasma concentration of glycolate and the urinary excretion of oxalate, the major metabolites of ethylene glycol, uniformly fell after the initiation of fomepizole therapy. Few adverse effects were attributable to fomepizole.

Conclusions In patients with ethylene glycol poisoning, fomepizole administered early in the course of intoxication prevents renal injury by inhibiting the formation of toxic metabolites.


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From Toxicology Associates (J.B., S.P., M.W., K.K.), Sections of Clinical Pharmacology and Toxicology (J.B., S.P.), Emergency Medicine (J.B., K.K.), and Pediatric Pharmacology (J.B., K.K.), University of Colorado Health Sciences Center, Denver; the Department of Pharmacology, Louisiana State University Medical Center, Shreveport (K.M.); and the Department of Emergency Medicine and the Central Pennsylvania Poison Center, Milton S. Hershey Pennsylvania State Geisinger Health System, Hershey (K.K.B., J.W.D.).

Address reprint requests to Dr. Brent at Toxicology Associates, 2555 S. Downing St., Suite 260, Denver, CO 80210.

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