Methanol and ethylene glycol poisoning
- Marco L A Sivilotti, MD, MSc, FRCPC, FACEP, FACMT
Marco L A Sivilotti, MD, MSc, FRCPC, FACEP, FACMT
- Professor of Emergency Medicine and of Biomedical & Molecular Sciences
- Queen's University, Kingston Canada
- James F Winchester, MD
James F Winchester, MD
- Professor of Medicine
- Icahn School of Medicine at Mount Sinai
- Section Editors
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Michele M Burns, MD, MPH
Michele M Burns, MD, MPH
- Section Editor — Pediatric Toxicology
- Assistant Professor of Pediatrics and Emergency Medicine
- Harvard Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Adult and Pediatric Emergency Medicine
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
Methanol and ethylene glycol poisonings cause dozens of fatal intoxications in the United States (US) annually, and even relatively small ingestions of these alcohols can produce significant toxicity. Rapid recognition and early treatment, including alcohol dehydrogenase inhibition, are crucial. A summary table to facilitate emergent management is provided (table 1).
Methanol and ethylene glycol are frequently found in high concentration in automotive antifreeze and de-icing solutions, windshield wiper fluid, solvents, cleaners, fuels, and other industrial products. Most serious poisonings occur following ingestion; inhalation and dermal exposures rarely cause toxicity.
Patients may ingest toxic alcohols as an ethanol substitute, to inflict self-harm, or by accident, sometimes following transfer from the original container. Multiple victim methanol poisonings can occur with illicit distillation ("moonshine") or occult substitution for ethanol. Methanol poisoning outbreaks with hundreds of victims are rare, but continue to occur around the globe, overwhelming available critical care and hemodialysis infrastructure [1,2].
To provide proper management, clinicians must understand the metabolic activation of these alcohols to their toxic acid metabolites, the limitations of available laboratory tests, and the indications for treatment with antidotes, with or without hemodialysis.
The diagnosis and management of methanol and ethylene glycol intoxication will be reviewed here. Isopropyl alcohol intoxication and a general approach to the poisoned adult or child are discussed separately. (See "Isopropyl alcohol poisoning" and "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)
- Zakharov S, Pelclova D, Urban P, et al. Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks. Ann Emerg Med 2016; 68:52.
- Rostrup M, Edwards JK, Abukalish M, et al. Correction: The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014. PLoS One 2016; 11:e0157256.
- d'Alessandro A, Osterloh JD, Chuwers P, et al. Formate in serum and urine after controlled methanol exposure at the threshold limit value. Environ Health Perspect 1994; 102:178.
- Kerns W 2nd, Tomaszewski C, McMartin K, et al. Formate kinetics in methanol poisoning. J Toxicol Clin Toxicol 2002; 40:137.
- Liesivuori J, Savolainen H. Methanol and formic acid toxicity: biochemical mechanisms. Pharmacol Toxicol 1991; 69:157.
- Moreau CL, Kerns W 2nd, Tomaszewski CA, et al. Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group. J Toxicol Clin Toxicol 1998; 36:659.
- Fraser AD. Clinical toxicologic implications of ethylene glycol and glycolic acid poisoning. Ther Drug Monit 2002; 24:232.
- Sivilotti ML, Burns MJ, Aaron CK, et al. Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol 2001; 39:627.
- Sivilotti ML, Burns MJ, McMartin KE, Brent J. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group. Ann Emerg Med 2000; 36:114.
- Jacobsen D, Hewlett TP, Webb R, et al. Ethylene glycol intoxication: evaluation of kinetics and crystalluria. Am J Med 1988; 84:145.
- Bove KE. Ethylene glycol toxicity. Am J Clin Pathol 1966; 45:46.
- Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol 1986; 1:309.
- Höjer J. Severe metabolic acidosis in the alcoholic: differential diagnosis and management. Hum Exp Toxicol 1996; 15:482.
- Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol 1997; 35:127.
- Malandain H, Cano Y. Interferences of glycerol, propylene glycol, and other diols in the enzymatic assay of ethylene glycol. Eur J Clin Chem Clin Biochem 1996; 34:651.
- Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol 1999; 37:537.
- Levine M, Curry SC, Ruha AM, et al. Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Ann Emerg Med 2012; 59:527.
- Casavant MJ, Shah MN, Battels R. Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics 2001; 107:113.
- Hassanian-Moghaddam H, Nikfarjam A, Mirafzal A, et al. Methanol mass poisoning in Iran: role of case finding in outbreak management. J Public Health (Oxf) 2015; 37:354.
- Shirey T, Sivilotti M. Reaction of lactate electrodes to glycolate. Crit Care Med 1999; 27:2305.
- Church AS, Witting MD. Laboratory testing in ethanol, methanol, ethylene glycol, and isopropanol toxicities. J Emerg Med 1997; 15:687.
- Gabow PA, Clay K, Sullivan JB, Lepoff R. Organic acids in ethylene glycol intoxication. Ann Intern Med 1986; 105:16.
- Eder AF, Dowdy YG, Gardiner JA, et al. Serum lactate and lactate dehydrogenase in high concentrations interfere in enzymatic assay of ethylene glycol. Clin Chem 1996; 42:1489.
- Morgan TJ, Clark C, Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate. Crit Care Med 1999; 27:2177.
- Porter WH, Crellin M, Rutter PW, Oeltgen P. Interference by glycolic acid in the Beckman synchron method for lactate: a useful clue for unsuspected ethylene glycol intoxication. Clin Chem 2000; 46:874.
- Brindley PG, Butler MS, Cembrowski G, Brindley DN. Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol. CMAJ 2007; 176:1097.
- Wallace KL, Suchard JR, Curry SC, Reagan C. Diagnostic use of physicians' detection of urine fluorescence in a simulated ingestion of sodium fluorescein-containing antifreeze. Ann Emerg Med 2001; 38:49.
- Sharma AN, O'Shaughnessy PM, Hoffman RS. Urine fluorescence: is it a good test for ethylene glycol ingestion? Pediatrics 2002; 109:345.
- Koga Y, Purssell RA, Lynd LD. The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices. Toxicol Rev 2004; 23:203.
- Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 1993; 31:81.
- Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002; 40:415.
- Lynd LD, Richardson KJ, Purssell RA, et al. An evaluation of the osmole gap as a screening test for toxic alcohol poisoning. BMC Emerg Med 2008; 8:5.
- Steinhart B. Case report: severe ethylene glycol intoxication with normal osmolal gap--"a chilling thought". J Emerg Med 1990; 8:583.
- Ammar KA, Heckerling PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap. Am J Kidney Dis 1996; 27:130.
- Purssell RA, Lynd LD, Koga Y. The use of the osmole gap as a screening test for the presence of exogenous substances. Toxicol Rev 2004; 23:189.
- Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med 2001; 38:653.
- Sivilotti ML. Methanol intoxication. Ann Emerg Med 2000; 35:313.
- Kostic MA, Dart RC. Rethinking the toxic methanol level. J Toxicol Clin Toxicol 2003; 41:793.
- Porter WH, Rutter PW, Bush BA, et al. Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol 2001; 39:607.
- De Leacy EA, Moxon LN, Ellis VM, et al. A report of accidental ethylene glycol ingestion in 2 siblings. Pathology 1995; 27:273.
- Baud FJ, Galliot M, Astier A, et al. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 1988; 319:97.
- Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 1999; 340:832.
- Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of methanol poisoning. N Engl J Med 2001; 344:424.
- Shannon M. Toxicology reviews: fomepizole--a new antidote. Pediatr Emerg Care 1998; 14:170.
- Battistella M. Fomepizole as an antidote for ethylene glycol poisoning. Ann Pharmacother 2002; 36:1085.
- Sivilotti ML. Ethanol: tastes great! Fomepizole: less filling! Ann Emerg Med 2009; 53:451.
- Dart RC, Borron SW, Caravati EM, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med 2009; 54:386.
- Lepik KJ, Levy AR, Sobolev BG, et al. Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole. Ann Emerg Med 2009; 53:439.
- Boyer EW, Mejia M, Woolf A, Shannon M. Severe ethylene glycol ingestion treated without hemodialysis. Pediatrics 2001; 107:172.
- Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia: outbreak in 154 patients. Clin Toxicol (Phila) 2007; 45:152.
- Zakharov S, Pelclova D, Navratil T, et al. Fomepizole versus ethanol in the treatment of acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning outbreak. Clin Toxicol (Phila) 2015; 53:797.
- Naraqi S, Dethlefs RF, Slobodniuk RA, Sairere JS. An outbreak of acute methyl alcohol intoxication. Aust N Z J Med 1979; 9:65.
- Burns MJ, Graudins A, Aaron CK, et al. Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med 1997; 30:829.
- Bekka R, Borron SW, Astier A, et al. Treatment of methanol and isopropanol poisoning with intravenous fomepizole. J Toxicol Clin Toxicol 2001; 39:59.
- Youssef GM, Hirsch DJ. Validation of a method to predict required dialysis time for cases of methanol and ethylene glycol poisoning. Am J Kidney Dis 2005; 46:509.
- McMurray M, Carty D, Toffelmire EB. Predicting methanol clearance during hemodialysis when direct measurement is not available. CANNT J 2002; 12:29.
- Burns AB, Bailie GR, Eisele G, et al. Use of pharmacokinetics to determine the duration of dialysis in management of methanol poisoning. Am J Emerg Med 1998; 16:538.
- Chow MT, Di Silvestro VA, Yung CY, et al. Treatment of acute methanol intoxication with hemodialysis using an ethanol-enriched, bicarbonate-based dialysate. Am J Kidney Dis 1997; 30:568.
- Dorval M, Pichette V, Cardinal J, et al. The use of an ethanol- and phosphate-enriched dialysate to maintain stable serum ethanol levels during haemodialysis for methanol intoxication. Nephrol Dial Transplant 1999; 14:1774.
- Ghosh A, Boyd R. Leucovorin (calcium folinate) in "antifreeze" poisoning. Emerg Med J 2003; 20:466.
- McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning. V. Role of formate metabolism in the monkey. J Pharmacol Exp Ther 1977; 201:564.
- Hantson P, Vanormelingen P, Lecomte C, et al. Fatal methanol poisoning and organ donation: experience with seven cases in a single center. Transplant Proc 2000; 32:491.
- López-Navidad A, Caballero F, González-Segura C, et al. Short- and long-term success of organs transplanted from acute methanol poisoned donors. Clin Transplant 2002; 16:151.
- Caravati EM, Erdman AR, Christianson G, et al. Ethylene glycol exposure: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005; 43:327.
- Woolf AD, Wynshaw-Boris A, Rinaldo P, Levy HL. Intentional infantile ethylene glycol poisoning presenting as an inherited metabolic disorder. J Pediatr 1992; 120:421.
- Shoemaker JD, Lynch RE, Hoffmann JW, Sly WS. Misidentification of propionic acid as ethylene glycol in a patient with methylmalonic acidemia. J Pediatr 1992; 120:417.
- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES OF OVERDOSE
- Physical examination
- Differential diagnosis
- Laboratory evaluation
- - Basic testing
- - Additional tests with toxic alcohol exposure
- Pitfalls in laboratory testing
- - Testing for methanol and ethylene glycol
- - Lactate
- - Urine testing
- - Plasma osmolal gap
- Overview of emergent management
- Airway, breathing, circulation
- Gastrointestinal decontamination
- Treatment with sodium bicarbonate
- Alcohol dehydrogenase inhibition
- - Approach and initiation
- - Fomepizole
- - Ethanol
- Cofactor therapy
- Preterminal care
- PEDIATRIC CONSIDERATIONS
- Younger children
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS