Literature
Clinical Pearls & Morning Reports
Published January 17, 2018
How does fomepizole compare to ethanol for the treatment of methanol or ethylene glycol poisoning?
Poisonings by the toxic alcohols (methanol, ethylene glycol, isopropanol, diethylene glycol, and propylene glycol) can cause cellular dysfunction and death, but symptoms may be nonspecific. History of exposure to one of the toxic alcohols is important, given the nonspecific clinical findings and the potential delay between exposure and their appearance. Read the latest NEJM Review Article here.
Clinical Pearls
Q: Are the “toxic alcohols” directly toxic?
A: The toxic alcohols are inebriating but are not directly toxic, except for isopropanol. Their toxic effects result fromtheir metabolites. Alcohol dehydrogenase is the critical enzyme that modulates the production of the toxic metabolites. Coingested ethanol, a competitive substrate for alcohol dehydrogenase, delays production of the toxic metabolites.
Q: Does a normal osmolal gap exclude the possibility of toxic alcohol poisoning?
A: A high anion-gap metabolic acidosis, an increased serum osmolal gap, or both can suggest that one of the toxic alcohols is present in the blood, but these abnormal laboratory results are not always present. A poisoned patient can present with both a normal or high osmolal gap and a normal or elevated serum anion gap.
Morning Report Questions
Q: What are some of the clinical findings associated with methanol and ethylene glycol poisoning?
A: The alcohols initially depress the sensorium and later produce organ dysfunction. Methanol is associated with decreased vision (in 29 to 72% of cases, occasionally producing blindness), pulmonary dysfunction, abdominal pain, coma, and, rarely, Parkinson-like symptoms. Clinical findings usually evolve over 6 to 24 hours but can be delayed as long as 72 to 96 hours if ethanol is coingested. Neurologic sequelae may ensue days or weeks after exposure. Ethylene glycol poisoning leads to formation of oxalate crystals, which deposit in the lungs, heart, and kidney and produce organ dysfunction. Cranial nerve damage, sometimes delayed for days, can also occur.
Q: How does fomepizole compare to ethanol for the treatment of methanol or ethylene glycol poisoning?
A: Ethanol has a high affinity for alcohol dehydrogenase, and intravenous ethanol, although not approved by the Food and Drug Administration (FDA), is often used for treatment. Advantages include its ready availability and low cost. Disadvantages include the need for compounding by a pharmacist for intravenous use, the need for frequent monitoring of serum concentrations, its effect in blunting the sensorium, and the need for hospitalization in the intensive care unit. Fomepizole (or 4-methylpyrazole) is a strong inhibitor of alcohol dehydrogenase (fomepizole has an affinity for alcohol dehydrogenase 8000 times that of ethanol) that received FDA approval for the treatment of ethylene glycol and methanol poisoning in 1997 and 2000, respectively, but it is not approved for the treatment of the other toxic alcohol poisonings. Formepizole is effective at low concentrations, has minimal side effects, and does not require monitoring in an intensive care unit. A systematic review of the literature from 1974 through August 2010 showed that mortality among patients who ingested methanol or ethylene glycol and received treatment with ethanol was 21.8% and 18.1%, respectively. Mortality among patients who ingested methanol or ethylene glycol and received treatment with fomepizole was 17.1% and 4.1%, respectively. Adverse events occurred more frequently with ethanol than with fomepizole (57% vs. 12%). The cost of fomepizole was often given as a reason to forgo its use. However, the introduction of generic forms has reduced the cost considerably. Thus, fomepizole is preferable for treatment of these poisonings, but ethanol is effective when fomepizole is not available.