Methanol Poisoning: Straightforward to Treat, but Not to Diagnose
ABSTRACT & COMMENTARY
Source: Liu JJ, et al. Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol 1998;36:175-181.
Methanol, a solvent found in antifreeze, windshield wiper fluid, and various paints and varnishes, can lead to blindness, seizures, coma, and death (mortality rate as high as 50%) when ingested. Liu and colleagues performed a retrospective analysis of methanol poisoning to identify prognostic factors related to clinical outcome, categorized as complete recovery, residual visual sequelae, and death.
Fifty patients from 1982-1992 were evaluated. All patients were treated with ethanol, bicarbonate, and hemodialysis. Eighteen patients (32% of total) died. Seven of the thirty-two survivors (22%) suffered visual sequelae, and twenty-five (78%) had complete recovery (though permanent neurologic sequelae in survivors was not documented). Statistically significant independent clinical indicators of mortality included seizure or coma on presentation (sensitivity 89%, specificity 91%, positive predictive value 84%, and negative predictive value 94%) and initial arterial pH less than 7.0 (sensitivity 94%, specificity 94%, positive predictive value 89%, and negative predictive value 97%). Low initial pH correlated with presence of visual symptoms at presentation, but not with permanent visual sequelae.
COMMENT BY FREDERIC H. KAUFFMAN, MD, FACEP
Alcohol dehydrogenase metabolizes methanol to formaldehyde, which in turn is metabolized to formic acid, resulting in the classic anion gap metabolic acidosis seen in patients with methanol ingestion. Formic acid is a mitochondrial toxin that inhibits cytochrome c oxidase activity, thereby leading to tissue hypoxia and the accumulation of lactic acid. In addition to aggressive correction of metabolic acidosis with sodium bicarbonate, therapy in the ED begins with oral or intravenous ethanol, a competitive inhibitor of alcohol dehydrogenase. Intravenous folate enhances the oxidation of formic acid to carbon dioxide, and hemodialysis effectively treats the acidosis and removes both methanol and formic acid.
In the past, much significance has been given to the presence of an osmol gap (freezing-point depression measured osmolality minus calculated osmolarity) in clinically significant methanol poisoning. Osmolarity is calculated using the equation: (2)(Na) + glucose/18 + BUN/2.8 + ethanol/4.6. Based upon the normal distribution of baseline osmol gaps in the general population, an osmol gap of greater than 10 mOsm is considered abnormal. Unfortunately, too many clinicians have assumed that an osmol gap less than 10 mOsm is "normal," and effectively rules out volatile alcohol poisoning. In fact, 95% of the population has a baseline osmol gap between -14 and 10 mOsm. As such, it is safe to say that an osmol gap greater than 10 mOsm in an individual patient is abnormal; however, a gap less than 10 mOsm may be abnormal depending on the patient's baseline osmol gap. For example, if the patient's baseline osmol gap is -10 mOsm, and using the above data his osmol gap is calculated to be +8 mOsm, a change from baseline of 18 mOsm has occurred, clearly making methanol poisoning a possibility. Other factors which may yield an osmol gap less than 10 mOsm in a patient with methanol poisoning include early presentation (where a limited amount of methanol has been absorbed) and late presentation (where most of the methanol has been metabolized to products which do not have osmotic activity). Finally, do not forget that small errors in the measurement of serum sodium concentration may falsely lower the osmol gap as well.1 It would have been nice if Liu et al presented the osmol gaps in their patients. Had they done so, it likely would have reinforced the fact that osmol gaps less than 10 mOsm do not rule out clinically significant methanol poisoning. The real key to the diagnosis is to think of the entity in patients with visual and/or neurologic complaints, coupled with an anion gap metabolic acidosis.
Reference
1. Hoffman RS. Fluid, electrolyte, and acid-base principles. In Goldfrank LR, et al (eds). Goldfrank's Toxicologic Emergencies. Norwalk, CT: Appleton and Lange; 1994:283-300.
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