Methanol (wood alcohol) is a common ingredient in many solvents, windshield-washing solutions, duplicating fluids, solid cooking fuel, and paint removers. It sometimes is used as an ethanol substitute by alcoholics. Periodically, mass poisonings occur when methanol is formed during incorrectly managed distillation processes or is intentionally added to fortify illicitly produced alcoholic beverages. Although methanol produces mainly inebriation, its metabolic products may cause metabolic acidosis, blindness, and death after a characteristic latent period of 6-30 hours.

1. Methanol is slowly metabolized by alcohol dehydrogenase to formaldehyde and subsequently by aldehyde dehydrogenase to formic acid (formate). Systemic acidosis is caused by both formate and lactate, whereas blindness is caused primarily by formate. Both ethanol and methanol compete for the enzyme alcohol dehydrogenase, and saturation with ethanol (or the antidote fomepizole) blocks the metabolism of methanol to its toxic metabolites.
2. Methanol crosses the placenta, and severe fetal methanol toxicity and death associated with maternal methanol poisoning has been reported.
3. Pharmacokinetics. Methanol is readily absorbed and quickly distributed to the body water (Vd = 0.6-0.77 L/kg). It is not protein bound. It is metabolized slowly by alcohol dehydrogenase via zero-order kinetics at a rate about one-tenth that of ethanol. The reported “half-life” ranges from 2.5 to 87 hours, depending on methanol serum concentration (the higher the serum level, the longer the half-life) and whether metabolism is blocked (eg, by ethanol or fomepizole). Only about 3% is excreted unchanged by the kidneys, and less than 10-20% through the breath. Endogenous formate half-life ranges from 1.9 to 9.3 hours; during dialysis, the half-life decreases to 1.5-3.1 hours.

1. Acute ingestion. The fatal oral dose of methanol is estimated to be 30-240 mL (20-150 g). The minimum toxic dose is approximately 100 mg/kg. Elevated serum methanol levels have been reported after extensive dermal exposure and concentrated inhalation.
2. Inhalation. The ACGIH-recommended workplace exposure limit (TLV-TWA) for inhalation is 200 ppm as an 8-hour time-weighted average, and the level considered immediately dangerous to life or health (IDLH) is 6,000 ppm.

1. In the first few hours after acute ingestion, methanol-intoxicated patients present with inebriation and gastritis. Acidosis is not usually present because metabolism to toxic products has not yet occurred. There may be a noticeable elevation in the osmol gap, but an osmol gap as low as 10 mOsm/L is still consistent with toxic concentrations of methanol.
2. After a latent period of up to 30 hours, severe anion gap metabolic acidosis, visual disturbances, blindness, seizures, coma, acute renal failure with myoglobinuria, and death may occur. Patients describe the visual disturbance as blurred vision, haziness, or “like standing in a snowfield.” Funduscopic examination may reveal optic disc hyperemia or pallor, venous engorgement, peri papilledema, and retinal or optic disc edema. The latent period is longer when ethanol has been ingested concurrently with methanol. Visual disturbances may occur within 6 hours in patients with a clear sensorium. Findings on magnetic resonance imaging (MRI) and computed tomography (CT), such as putaminal necrosis and hemorrhage, are nonspecific and can change over time and therefore are not diagnostic of methanol poisoning.

Usually is based on the history, symptoms, and laboratory findings because stat methanol levels are rarely available. Calculation of the osmol and anion gaps can be used to estimate the methanol level and predict the severity of the ingestion. A large anion gap not accounted for by elevated lactate suggests possible methanol (or ethylene glycol) poisoning because the anion gap in these cases is mostly nonlactate.

1. Specific levels
   1. Serum methanol levels higher than 20 mg/dL should be considered toxic, and levels higher than 40 mg/dL should be considered very serious. After the latent period, a low or nondetectable methanol level does not rule out serious intoxication in a symptomatic patient because all of the methanol may already have been metabolized to formate. If serum methanol levels are not available, an estimation can be calculated from the osmol gap (see Table I-23); an osmol gap greater than 10 mOsm/L is consistent with a toxic methanol level.
   2. Elevated serum formate concentrations may confirm the diagnosis and are a better measure of toxicity, but formate levels are rarely available. Note: if coingested ethanol is transiently preventing methanol metabolism, the formate level may be low initially.
2. Other useful laboratory studies include electrolytes (and anion gap), glucose, BUN, creatinine, serum osmolality and osmol gap calculation, blood gases, ethanol level, and lactate level.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat coma and seizures if they occur.
   3. Treat metabolic acidosis with IV sodium bicarbonate. Correction of acidosis should be guided by arterial blood gases.
2. Specific drugs and antidotes
   1. Administer fomepizole or ethanol to saturate the enzyme alcohol dehydrogenase and prevent formation of the toxic metabolites of methanol. Therapy is indicated in patients with the following:
      1. A history of significant methanol ingestion when methanol serum levels are not immediately available and the osmol gap is greater than 10 mOsm/L.
      2. Metabolic acidosis (arterial pH <7.3, serum bicarbonate <20 mEq/L) and an osmol gap greater than 10 mOsm/L not accounted for by ethanol or isopropanol.
      3. A methanol blood concentration greater than 20 mg/dL.
   2. Leucovorin or folic acid may enhance the conversion of formate to carbon dioxide and water. A suggested dose of either leucovorin or folic acid is 1 mg/kg (up to 50 mg) IV every 4-6 hours.
3. Decontamination. Aspirate gastric contents if this can be performed within 30-60 minutes of ingestion. Activated charcoal is not likely to be useful because the effective dose is very large and methanol is absorbed rapidly from the GI tract.
4. Enhanced elimination. Hemodialysis rapidly removes both methanol (half-life reduced to 3-6 hours) and formate.
   1. The indications for dialysis in suspected methanol ingestion include elevated serum methanol level, elevated osmol gap, severe acidosis, coma, new visual deficits, kidney dysfunction or seizures (see Table II-36).
   2. Dialysis, fomepizole, or ethanol should be continued until the methanol concentration is less than 20 mg/dL or the osmol and anion gaps are normalized.