title: American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.
abstract: BACKGROUND
  Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes.
  Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells.
  
  
  METHODS
  Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness.
  
  
  RESULTS
  For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost.
  
  
  CONCLUSIONS
  The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.
authors.affiliation: American Academy of Clinical Toxicology, Harrisburg, Pennsylvania 17105-8820, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Barceloux
authors.forename: G Randall
authors.initials: GR
authors.lastname: Bond
authors.forename: Edward P
authors.initials: EP
authors.lastname: Krenzelok
authors.forename: Hannah
authors.initials: H
authors.lastname: Cooper
authors.forename: J Allister
authors.initials: JA
authors.lastname: Vale
mesh_terms: D000431:Ethanol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077604:Fomepizole; D005561:Formates / Q000633:toxicity; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D000432:Methanol / Q000506:poisoning*; D011041:Poisoning / Q000628:therapy; D017410:Practice Guidelines as Topic; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006435:Renal Dialysis
chemical_list: D005561:Formates; D011720:Pyrazoles; C030544:formic acid; D000431:Ethanol; D000077604:Fomepizole; D002955:Leucovorin; D000432:Methanol