Fomepizole for the treatment of ethylene glycol poisoning

Background Ethylene glycol poisoning causes metabolic acidosis and renal fa ilure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hem odialysis. We studied the efficacy of fomepizole, a new inhibitor of alcoho l dehydrogenase, in the treatment of ethylene glycol poisoning. Methods We administered intravenous fomepizole to 19 patients with ethylene glycol poisoning (plasma ethylene glycol concentration, greater than or eq ual to 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-ba se 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 bicarbon ate concentration, 72.9 mmol per liter). Acid-base status tended to normali ze within hours after the initiation of treatment with fomepizole. One pati ent with extreme acidosis died. In nine patients, renal function decreased during therapy; at enrollment, all nine had high serum creatinine concentra tions and markedly elevated plasma glycolate concentrations (greater than o r equal to 97.7 mg per deciliter [12.9 mmol per liter]). None of the 10 pat ients with normal serum creatinine concentrations at enrollment had renal i njury during treatment; all 10 had plasma glycolate concentrations at or be low 76.8 mg per deciliter (10.1 mmol per liter). Renal injury was independe nt of the initial plasma ethylene glycol concentration. The plasma concentr ation of glycolate and the urinary excretion of oxalate, the major metaboli tes of ethylene glycol, uniformly fell after the initiation of fomepizole t herapy. Few adverse effects were attributable to fomepizole. Conclusions In patients with ethylene glycol poisoning, fomepizole administ ered early in the course of intoxication prevents renal injury by inhibitin g the formation of toxic metabolites. (N Engl J Med 1999; 340:832-8.) (C) 1 999, Massachusetts Medical Society.