The Antidote for Antifreeze, Something Old or Something New?

ABSTRACT & COMMENTARY

Source: Brent J, et al. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 1999;340:832-838.

Ethylene glycol poisoning causes metabolic acidosis and renal failure and may cause death. Traditionally, treatment has focused on inhibition of alcohol dehydrogenase with intravenous or oral ethanol and adjunctive hemodialysis. Brent and associates studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of ethylene glycol poisoning. Over a two-year period they collected data on 19 patients who met the definition of ethylene glycol poisoning and had a plasma ethylene glycol concentration of 20 mg/dL or more. Seventeen patients who met specific criteria also underwent hemodialysis. Treatment was continued until plasma ethylene glycol concentrations were less than 20 mg/dL.

Fifteen of the patients initially had acidosis. This tended to normalize within hours after the initiation of treatment with fomepizole. Interestingly, the nine patients who developed renal impairment had high serum creatinine concentrations and markedly elevated plasma glycolate concentrations at enrollment (> 97.7 mg/dL). 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/dL. Few adverse effects were attributable to fomepizole.

Comment by Richard Hamilton, MD, FAAEM, ABMT

There are an estimated 5000 exposures to ethylene glycol per year, and each clinician who manages these cases is faced with the same old question about the same old antidote: "do I start an ethanol drip or not?" The reluctance to start this therapy is based on many difficulties. First, many hospitals are unable to determine an ethylene glycol level in a clinically useful period of time and clinicians must make this decision on an unreliable ingestion history and an only slightly more reliable test, the osmolal gap. Second, ethanol drips are uncommon orders for hospital pharmacies, and difficulties and uncertainty are the rule. Third, the ethanol drip is difficult to manage. Ethanol must be maintained at a serum level of about 100 mg/dL, requires frequent monitoring, and kinetics can vary widely depending on premorbid conditions. In addition, ethanol metabolism can cause hypoglycemia, respiratory depression, and hypovolemia.

Now clinicians will have to ask themselves a new question about a new antidote, fomepizole. This antidote, originally known as 4-methylpyrazole, was first touted as an antidote for toxic alcohol ingestions 10 years ago. It appears safe, has been demonstrated to be effective in bench, animal, and human studies, and is extremely simple to administer. Then why isn’t the answer to this question an automatic yes? Like everything else in medicine at the end of the millennium, we are inhibited by cost. A course of fomepizole for an ethylene glycol-poisoned patient costs $4,000. To compare, oral loading and maintenance of ethanol is one-hundredth the cost and comes in a variety of bottles and flavors. Proponents of both therapies can make lucid fiscal arguments why either antidote is superior. I have this antidote available to me at many but not all of the hospitals where I function as a bedside consulting toxicologist, and have used it with great satisfaction. Each hospital must decide whether they can afford fomepizole, and, oddly enough, I would recommend this antidote to the hospitals who anticipate the greatest difficulty in obtaining toxicology consultation and emergent hemodialysis. It certainly is the least complicated therapy to initiate and carries the greatest chance of success for the patient.