Methanol Poisoning

Methanol toxicity results not from methanol itself, which is relatively non-toxic, but from its metabolism via alcohol dehydrogenase to formaldehyde, and subsequently via aldehyde dehydrogenase to formic acid, the toxic metabolite responsible for the characteristic metabolic acidosis and, in particular, the optic nerve toxicity that defines this poisoning.

Exposure typically occurs through ingestion of contaminated or illicitly produced alcoholic beverages, industrial solvents, or windshield washer fluid, and outbreaks are recognized periodically in settings with unregulated alcohol production.

There is characteristically a latent period of 12 to 24 hours (longer if ethanol is co-ingested, since ethanol competitively inhibits methanol metabolism) between ingestion and the onset of significant toxicity, during which the patient may appear relatively well or only mildly intoxicated, reflecting the time needed for toxic metabolite accumulation.

• Early, non-specific symptoms: nausea, vomiting, abdominal pain, headache, and a degree of inebriation similar to ethanol intoxication.
• As formic acid accumulates: visual disturbance is the hallmark feature, classically described as "looking at a snowfield," progressing from blurred vision to photophobia and, in severe cases, permanent blindness from direct optic nerve toxicity.
• Severe poisoning causes a profound anion gap metabolic acidosis, confusion, seizures, and coma, with a significant risk of death from cardiovascular collapse in the most severe cases.

• A serum methanol level confirms exposure and quantifies severity, though this test is not always rapidly available, and treatment decisions often need to be made on clinical grounds and surrogate markers before a level returns.
• Venous or arterial blood gas characteristically shows a severe, high anion gap metabolic acidosis.
• The osmolar gap (measured serum osmolality minus calculated osmolality) is a valuable surrogate marker in the absence of a rapidly available methanol level: an elevated osmolar gap early after ingestion suggests the presence of unmetabolized parent alcohol, while, importantly, the osmolar gap narrows and the anion gap widens as metabolism proceeds and toxic acid accumulates, meaning a normal osmolar gap does not exclude significant, already evolved toxicity later in the course.
• Formal ophthalmological assessment, including fundoscopy for optic disc hyperemia or pallor, supports the diagnosis where visual symptoms are present.
• Lactate should be checked, as should renal function.

Differentials include diabetic ketoacidosis and other causes of a high anion gap metabolic acidosis, ethylene glycol poisoning (which shares a very similar presentation and management approach, differing mainly in the target organ of toxicity), and simple ethanol intoxication.

• Alcohol dehydrogenase blockade is the cornerstone of specific treatment, preventing further conversion of methanol into its toxic metabolites and allowing the relatively harmless parent methanol to be excreted or dialyzed.
• Fomepizole, a direct alcohol dehydrogenase inhibitor, is the preferred antidote where available, given intravenously.
• Where fomepizole is unavailable, an intravenous ethanol infusion achieves the same effect by competitively saturating alcohol dehydrogenase, titrated to maintain a specific target blood ethanol concentration, though this requires more intensive monitoring than fomepizole and carries its own sedative and metabolic risks.
• Sodium bicarbonate is given to correct the severe metabolic acidosis, which is important both for its own sake and because a less acidic environment reduces the proportion of formic acid in its more toxic, non-ionized form.
• Hemodialysis is indicated for severe poisoning (significant acidosis, visual symptoms, high methanol level, or renal impairment), since it removes both methanol and its toxic metabolites directly and corrects the acidosis more rapidly than medical management alone; alcohol dehydrogenase blockade should be continued through dialysis, with dosing adjusted accordingly.
• Folate or folinic acid is given as an adjunct, since it enhances the metabolism of formic acid to less toxic, more readily excreted products.

Referral: poison control or toxicology service urgently for all suspected cases; nephrology and ICU for hemodialysis; ophthalmology for assessment and follow up of visual toxicity.