How do fomepizole and ethanol compare for treating ethylene glycol poisoning?

Bottom line: Based on decades of experience and success in the treatment of ethylene glycol poisoning, ethanol drip is a valuable and much less expensive intervention to prevent complications from this ingestion.  However, appropriate levels should be maintained during therapy.  Fomepizole, while significantly more expensive, may be easier for nursing staff to administer to patients and an acceptable therapy for ethylene glycol ingestion.

Summary:    Ethylene glycol poisoning.  In: DynaMed.

American Academy of Clinical Toxicology practice guidelines.  J Toxicol Clin Toxicol 1999;37(5):537

Administration of ethanol has been used for treatment of ethylene glycol poisoning since demonstration of its use (JAMA 1965;194:173–175 ) Ethanol competes with ethylene glycol and inhibits metabolism of ethylene glycol to toxic metabolites by blocking the receptor sites of alcohol dehydrogenase.  Recommended dosages are outlined in DynaMed and the guidelines; the goal is to maintain serum ethanol 100-150 mg/dL.

N Engl J Med. 2001; 344 (6): 424-429.
Fomepizole (4-methylpyrazole) inhibits alcohol dehydrogenase which deters formation of the acid byproducts. Evidence of efficacy is based on non-randomized trials of patients presenting with methanol poisoning.  The cited multicenter study (Methylpyrazole for Toxic Alcohols Study) enrolled patients > age 12 with serum methanol ≥ 20 mg/dL over a 2 year period.  11 patients meeting inclusion criteria, received IV fomepizole, oxygenation and supportive therapy (fluids, electrolytes); dialysis after loading dose was administered for patients with initial pH<7.1 or unable to maintain pH of at least 7.3.  RESULTS:  Median duration of treatment was 30 hours (range 0.5 to 60).  Two patients died from methanol poisoning; they were comatose with severe acidosis at presentation.  Remaining 9 patients had no visual deficiencies from the methanol.  Adverse reactions reported in one patient (phlebitis, dyspepsia, anxiety, agitation, hiccups, a reaction at the infusion site, transient tachycardia, transient rash, and others.)  All resolved.

The evidence for each of these treatments is based on non-randomized studies.

There are no prospective studies directly comparing morbidity and mortality outcomes of administering fomepizole v. ethanol in patients with methanol poisoning.

The AACT recommendations, based on quasi-experimental studies and expert opinion are outlined in DynaMed Treatment section and are summarized in Table 2 (p. 539) of the guidelines.  Guidelines recommend fomepizole over ethanol in any of the following situations:

  • Ingestion of multiple substances with depressed level of consciousness.
  • Altered consciousness.
  • Lack of adequate intensive care staffing or laboratory support to monitor ethanol administration.
  • Relative contraindication to ethanol.
  • Critically-ill patient with an anion gap-metabolic acidosis of unknown etiology and potential exposure to ethylene glycol.
  • Patients with active hepatic disease.

In the same table, guidelines recommend ethanol over fomepizole if the patient has hypersentivity to fomepizole or if fomepizole is unavailable.

A retrospective review of adverse drug events (ADE), report that ethanol is associated with a greater rate of ADEs than fomepizole, suggesting that one possible factor may be the difficulty of maintaining desired level of serum ethanol through the course of treatment and respiratory depressive effects of ethanol.

Lepik KJ, et al.  Medication errors associated with the use of ethanol and fomepizole as antidotes for methanol and ethylene glycol poisoning.  Clin Toxicol (Phila). 2011 Jun;49(5):391-401.

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About Amy

Clinical Informationist at EUH Branch Library
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