Methanol Poisoning
Methanol is the simplest of alcohols, with the chemical formula CH3OH. It is also known as wood alcohol, wood spirit, wood naphtha, carbinol, or methylhydrate. It is a common cause of poisoning. Methanol resembles ethanol in taste, odor and intoxicating properties and is less expensive to purchase. Methanol intoxication most commonly follows ingestion of automotive windshield-washer fluid, duplicating fluid, nonpermanent antifreeze, glass cleaners, solvents, paint remover and embalming fluid.
Ingested methanol is completely absorbed, reaching peak blood concentration about 30 to 60 minutes after ingestion. After absorption, it is distributed in total body water (0.6 L/kg) and may be concentrated in the vitreous humor and cerebrospinal fluid. Toxic exposure can also arise from inhalation or prolonged skin contact.
The toxic dose of methanol is highly variable. The fatal dose is commonly stated to be 100 mL, but some patients have died after drinking 6 mL and others have survived after drinking 500 mL. Usually there is a lag time of 12 hours between ingestion and onset of symptoms. Symptoms may be delayed as long as 72 to 96 hours if ethanol is coingested. Symptoms include nausea, vomiting, abdominal pain, visual disturbances, headache, generalized weakness, seizures, CNS depression and coma. The most worrisome long-term complication in survivors is blindness.
Approximately 20% of methanol is eliminated unchanged by the lungs and kidneys. The remainder is metabolized in the liver. Alcohol dehydrogenase converts methanol to formaldehyde, which is almost immediately converted to formic acid by aldehyde dehydrogenase. Most of the pathologic effects of methanol ingestion are due to accumulation of formic acid. It inhibits aerobic metabolism and increases anaerobic glycolysis and lactate production, causing a severe metabolic acidosis. Blood pH often ranges between 6.8 and 7.3. Poorer outcomes are associated with more severe acidosis.
Most hospital laboratories do not measure methanol levels. However, other laboratory tests are helpful in making the diagnosis of methanol poisoning. Electrolytes reveal a low bicarbonate and elevated anion gap, consistent with metabolic acidosis. Anion gap rises as methanol is metabolized to formic acid.
Measurement of serum osmolality and calculation of the osmolal gap are also useful. Accumulation of the alcohol increases the serum osmolality and the osmolal gap, which is the difference between the serum osmolality, measured by freezing-point depression and calculated serum osmolarity. The osmolal gap varies during the course of intoxication. Accumulation of the parent alcohol initially elevates the osmolal gap, but as metabolism progresses, osmolal gap decreases.
The expected normal osmolal gap is 10 to 20 mOsm per kilogram of water. An osmolal gap greater than 20 mOsm/kg is consistent with ingestion of a foreign substance (see Osmolality for further details). A normal osmolal gap cannot be used to rule out toxic alcohol ingestion because some patients with toxic alcohol poisonings have osmolal gaps within the normal range.
According to the American Academy of Clinical Toxicology guidelines, hemodialysis should be considered in patients with metabolic acidosis (pH <7.3), methanol level of 50 mg/dL or higher, visual disturbances, renal failure or refractory electrolyte imbalance. Other treatment modalities include competitive inhibition of alcohol dehydrogenase using ethanol or fomepizole.
Reference
Kraut JA and Mullins ME. Toxic Alcohols. New Engl J Med 2018;378:270-80.
