Rethinking the toxic methanol level.
BACKGROUND
Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been offered nor has the time of the exposure been addressed. For instance, no distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from ingestion. We analyzed all published cases of methanol poisoning to determine the applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically those arriving early for care (within 6 hr) with a peak or near-peak blood methanol concentration.


METHODS
Using predefined search criteria, a systematic review of the world literature was performed using MEDLINE and EMBASE. In addition, each article's references were hand searched for pre-1966 articles, as were fatality abstracts from all U.S. poison centers. Human cases were included if they reported a known time of a single methanol exposure, acid-base data, blood methanol, and blood ethanol (if not acidotic).


RESULTS
Dating to 1879, 372 articles in 18 languages were abstracted using a standard format; 329 articles (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met inclusion criteria. Only 22 of these patients presented for care within 6hr of ingestion with an early methanol level. All but 1 patient was treated with an inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a methanol level > or = 126 mg/dL. The patient that did not receive an ADH inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was given folate alone and never became acidotic. Intra and inter-rater reliability were 0.95.


CONCLUSIONS
Nearly all reports of methanol poisoning involve acidotic patients far removed from ingestion. The small amount of data regarding patients arriving early show that 126 mg/dL is the lowest early blood methanol level ever clearly associated with acidosis. Contrary to conventional teaching, there are case reports of acidosis after only a few hours of ingestion. The data are insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient arriving early for care. Prospective studies are necessary to determine if such patients may be managed without antidotal therapy or dialysis.
Kostic
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MA
Rocky Mountain Poison and Drug Center, Denver Health Authority, Denver, Colorado 80230, USA. makostic@mar.med.navy.mil
Dart
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D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use; D001639:Bicarbonates / Q000097:blood; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077604:Fomepizole; D006801:Humans; D008297:Male; D000432:Methanol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use; D016896:Treatment Outcome
D000931:Antidotes; D001639:Bicarbonates; D011720:Pyrazoles; D000077604:Fomepizole; D000432:Methanol