Describe methanol poisoning.

Mechanism and the Latent Period

• Methanol (methyl alcohol, wood spirit) is used as an industrial solvent, in antifreeze, paint remover and varnish, and as a denaturant for ethanol. In India it is important chiefly as an adulterant of illicitly distilled liquor, and causes recurrent mass-casualty "hooch tragedies" in which dozens or hundreds die or are blinded from a single batch
• Methanol itself is relatively harmless. The toxicity is entirely due to its metabolites: alcohol dehydrogenase converts it to formaldehyde, and aldehyde dehydrogenase then to formic acid (formate), which is the agent of both the acidosis and the blindness
• This explains the latent period of 12 to 24 hours before symptoms appear — the time required for metabolism — which is prolonged, sometimes to several days, if ethanol was consumed at the same time, since ethanol competes for the same enzyme. The patient may therefore present feeling entirely well, which is the central clinical trap
• Formate inhibits cytochrome oxidase, producing a histotoxic anoxia, and is selectively toxic to the optic nerve and the retina; it also accumulates to cause a profound acidosis
• Fatal dose — about 60 to 240 mL; but blindness may follow as little as 10 mL

Treatment

• The principle is to block alcohol dehydrogenase, preventing the formation of formate, and then to remove the methanol and the formate already present
• Ethanol — the classical antidote, and the one available everywhere: it has a 10 to 20 times greater affinity for alcohol dehydrogenase and so competitively blocks methanol metabolism. Given orally or intravenously to maintain a blood ethanol of about 100 to 150 mg/dL
• Fomepizole (4-methylpyrazole) — the modern agent, a direct inhibitor of alcohol dehydrogenase; more reliable, without the sedation and hypoglycaemia of ethanol, but expensive and often unavailable
• Sodium bicarbonate — in generous amounts, both to correct the acidosis and because alkalinisation converts formic acid to the formate ion, which does not cross into tissues and is renally excreted
• Folinic acid (or folic acid) — a cofactor for the enzyme that converts formate to carbon dioxide and water, so it accelerates the elimination of formate
• Haemodialysis — removes both methanol and formate efficiently, and corrects the acidosis. Indicated for severe acidosis, any visual symptoms, a high methanol level, or renal failure. The ethanol infusion must be continued and increased during dialysis, since ethanol is dialysed out as well
• Supportive care — ventilation, management of convulsions, and ophthalmological assessment and follow-up

Applied Aspects

• Treat on the exposure, not on the symptoms; in an outbreak everyone who drank from the batch is assessed and treated, since the latent period means the sickest may present last
• Measure the anion gap and the osmolal gap; a raised osmolal gap early and a rising anion gap later is the pattern, and it is available in any hospital that can do basic biochemistry
• Give ethanol if fomepizole is unavailable — any ethanol, by any route — since blocking the enzyme is what preserves vision and delay is measured in retinal ganglion cells
• Give bicarbonate generously; the acidosis is severe and alkalinisation itself reduces tissue formate
• Increase the ethanol during dialysis, which removes it along with the methanol — a step routinely forgotten
• Report the outbreak immediately; a hooch tragedy is a public health emergency, the batch is still being sold, and identifying the source prevents further deaths
• Preserve blood, urine and the liquor itself; the prosecution of those responsible depends on demonstrating methanol in the sample and in the drink