methanol poisoning

see also:

• toxicology
• ethylene glycol poisoning
• ethanol (alcohol and alcohol withdrawal)

• methanol is a colourless and flammable liquid often used to produce fuel, insecticides, paint strippers, antifreeze, plastics, petrol and solvents and is the primary component of windshield washer fluid.
• methanol is indistinguishable from ethanol in taste but is poisonous to humans even in small amounts such as 10mL while 15-100mL can be fatal in adults
• methanol poisoning from use in cocktails is rare in Australia however it is much more common in Asian countries and mainly affects the poorest of the locals with thousands allegedly being blinded or suffering brain damage without international reporting of these instances
• alcohol distillers discard the initial part of the distil - the foreshots - as this contains most of the methanol

• peak plasma concentrations of methanol occur within 30 to 60 minutes of oral ingestion
• rapidly distributed and has a volume of distribution of 0.7 L/kg
• methanol is metabolized by the same enzymes as is ethanol however it is broken down to formaldehyde by alcohol dehydrogenase and then complete conversion to formic acid via aldehyde dehydrogenase
• methanol elimination half-life is 24 h via the renal route and is dialysable
• formate toxicity:
  • inhibits mitochondrial cytochrome c oxidase, causing hypoxia at the cellular level, and severe anion gap metabolic acidosis with late lactic acidosis adding to the derangement, among a variety of other metabolic disturbances
  • a consequence of increasing acidosis is the increased formation of the unionised state of formic acid that is more readily taken up into the CNS
  • optic nerves are particularly susceptible to the effects of formic acid since they have few mitochondria and are susceptible to histiotoxic hypoxia

• see also https://en.wikipedia.org/wiki/List_of_methanol_poisoning_incidents

• usually adult males
• over 1700 cases in the US in 2013

• methylated spirits is ethanol made poisonous by the addition of methanol so it can be sold as a solvent, etc
• when desperate chronic alcoholics may consume methylated spirits

• methanol is produced by fermenting fruit with high pectin content and can inadvertently be consumed if this is not considered and managed
• since 2019 when Médecins Sans Frontières (MSF) started tracking suspected methanol poisonings, they believe there have been 943 incidents leading to nearly 13,000 deaths
• reported incidents in 12 months to Nov 2024 according to MSF:
  • total of 58 suspected methanol poisoning incidents affecting 1200 people and 406 deaths
  • 24 in Indonesia
  • 9 in India including an incident in October that resulted in 65 deaths
  • 4 each in Bangladesh and Pakistan
  • 3 in Iran including one in September that impacted 160 people and left 26 dead
  • 2 each in Kenya and Tunisia
  • 1 in Laos - the Nov 2024 event at least 4 tourists died (two Danish and two Australian young women) and at least 10 others developed symptoms
  • 1 each in Cambodia and Malawi

• initial transient symptoms of CNS depression similar to drinking equivalent amounts of ethanol
• latent period of 1-12 hrs
• main symptoms of severe methanol poisoning may not appear until 10-30 hours after ingestion
  • headache
  • tachycardia
  • tachypnoea
  • dizziness
  • vomiting
  • photophobia
  • cerebral oedema resulting in seizures, confusion and coma
    • extrapyramidal movement disorders are often a consequence of serious CNS toxicity in those that recover
  • late elevation of serum lactate occurs due to the uncoupling of cytochrome oxidase by formate
  • visual impairments typically “snowstorm vision” or total loss of vision
    • dilated pupils, hyperaemia of the optic disc, retinal oedema
    • papilloedema is characteristic with progressive demyelination and up to one third of patient have irreversible visual complications
  • may cause permanent blindness due to destruction of the optic nerve, brain damage (subcortical white matter haemorrhages and putaminal hemorrhages), severe acidosis, renal and other organ failure, coma, respiratory failure and death

• EARLY suspicion is critical as the treatment is to PREVENT the metabolism of methanol as soon as possible
  • blood gases can aid diagnosis
    • osmolal gap, anion gap metabolic acidosis
• EARLY reduction of metabolism to formic acid:
  • EARLY IV fomepizole
    • fomepizole (4-methylpyrazole) is a competitive inhibitor of alcohol dehydrogenase
    • concurrent use with ethanol is contraindicated because fomepizole is known to prolong the half-life of ethanol via inhibiting its metabolism
    • loading dose of 15 mg/kg should be administered, followed by doses of 10 mg/kg every 12 h for 4 doses, then 15 mg/kg every 12 h thereafter until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL, and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes.
  • EARLY IV ethanol infusion if fomepizole is not available
    • ethanol competitively blocks the formation of toxic metabolites by having a higher affinity (up to 20 times) for alcohol dehydrogenase and blocking the receptor sites.
    • inhibition is said to be complete with blood ethanol concentrations of around 22 mmol/L (100 mg/dL, 0.1 g%).
    • 7.6-10ml/kg of 10% ethanol (v/v) in 5% dextrose given iv over 30min
      • this equates to 4 standard drinks for an adult or 0.6g/kg
• removal of methanol before it is metabolized
  • consider EARLY haemodialysis
• adjunctive Rx
  • general supportive care
  • consider sodium bicarbonate, folate and thiamine