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Abstract & Commentary
Synopsis: Fomepizole, a new inhibitor of alcohol dehydrogenase, can prevent renal injury in patients with ethylene glycol poisoning if administered soon after ingestion.
Source: Brent J, et al. N Engl J Med 1999;340: 832-838.
Ethylene glycol poisoning can be one of the more devastating ingestion-related problems encountered in critical care. This article reports a clinical evaluation of fomepizole, a new inhibitor of alcohol dehydrogenase, in patients with acute ethylene glycol poisoning.
Intravenous fomepizole was administered to 19 patients with ethylene glycol poisoning in this multicenter case series. The patients had severe poisoning, with plasma ethylene glycol concentrations of at least 20 mg/dL, and 15 had metabolic acidosis (mean initial serum bicarbonate, 12.9 mmol/L). Fomepizole was given as a loading dose of 15 mg/kg body weight, followed by 10 mg/kg every 12 hours for 48 hours, after which the dose was increased to 15 mg/kg every 12 hours because of increased metabolism of the drug. Hemodialysis was used if arterial pH fell below 7.10, if arterial pH or serum bicarbonate fell beyond threshold levels despite intravenous bicarbonate invusion, if the initial plasma ethylene glycol concentration exceeded 50 mg/dL, or if the serum creatinine increased by 1 mg/dL or more.
Acid-base status tended to normalize within hours of initiation of treatment with fomepizole. One patient with severe acidosis died. Renal function worsened in nine of the 19 patients during therapy. In these nine patients, serum creatinine concentrations were markedly elevated, as were concentrations of plasma glycolate. If serum creatinine was normal at the start of fomepizole therapy, renal dysfunction did not subsequently develop. Renal injury was independent of the initial ethylene glycol concentration, but correlated with plasma glycolate levels. Plasma glycolate and urinary oxalate excretion, both measures of ethylene glycol metabolites, fell in all the patients once therapy with fomepizole was initiated. Fomepizole was well tolerated by the patients, with no adverse effects definitely resulting from its administration; episodes of bradycardia in one patient, seizures in two patients, and headaches in two patients were classified as possibly related to the drug.
COMMENT BY DAVID J. PIERSON, MD, FACP, FCCP
This study’s results suggest that fomepizole is a safe and effective antidote in the treatment of ethylene glycol poisoning, one of the most serious ingestions encountered in the ICU. This drug may represent a genuine advance over the time-honored standard therapy of intravenous ethanol. Potential advantages include more predictable metabolism and fewer adverse effects, including avoidance of changes in the patient’s mental status. This paper reports the collected yet still anecdotal experience of Brent and colleagues. A prospective controlled trial comparing fomepizole with traditional ethanol therapy would better justify the widespread adoption of this new agent as standard care.
a. renal injury correlated with initial plasma ethylene glycol level.
b. there was no correlation between renal damage and plasma glycolate level.
c. mortality was 32%.
d. adverse effects limited the use of fomepizole.
e. None of the above