Diagnosis and Management of Ethylene Glycol Ingestion

  • Christine Martinek Brent
  • Robert W. ShafferEmail author


Ethylene glycol is an osmotically active organic alcohol responsible for nearly 6000 intentional and accidental ingestions annually. It may be found in many industrial and household products including antifreeze and de-icing solutions, brake and hydraulic fluids, and window cleaners. Ethylene glycol, itself, has little toxicity but its metabolites can cause serious morbidity and mortality.

Initial effects from ethylene glycol ingestion may resemble intoxication from ethanol, and patients may exhibit dysarthria, ataxia, confusion, stupor and even coma. The parent compound is metabolized in the liver via alcohol dehydrogenase and aldehyde dehydrogenase resulting in the production of glycolic acid. This metabolite is chiefly responsible for the anion-gap acidosis that develops, and can exert significant cardiopulmonary toxicity. A small amount of glycolic acid is further metabolized into oxalate, which leads to calcium oxalate deposition in renal tubules and subsequent renal injury.

The diagnosis of ethylene glycol poisoning can be challenging, as patients may not be forthcoming, or may present too altered to provide a history of ingestion. Ethylene glycol levels may not be readily available at the treating institution. Either a high index of suspicion, or the presence of an unexplained osmolal gap or anion gap acidosis, should prompt empiric treatment to maximize favorable outcomes. Enzymatic inhibition of alcohol dehydrogenase through the use of fomepizole or ethanol is the cornerstone of successful management. In later presentations where a significant anion gap acidosis has developed, or when renal injury is apparent, hemodialysis must be considered.


Ethylene glycol Antifreeze Toxic alcohol Fomepizole Ethanol Glycolic acid Glycolate Oxalic acid Oxalate Anion gap Osmolar gap Osmolal gap Metabolic acidosis Overdose Acute renal failure 


  1. 1.
    McQuade DJ, Dargan PI, Wood DM. Challenges in the diagnosis of ethylene glycol poisoning. Ann Clin Biochem. 2013;51(2):167–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Buchanan JA, Alhelail M, Cetaruk EW, Schaeffer TH, Palmer RB, Kulig K, et al. Massive ethylene glycol ingestion treated with fomepizole alone—a viable therapeutic option. J Med Toxicol. 2010;6(2):131–4.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Hantson P. Indicators of poor prognosis in toxic alcohols poisoning. Toxicol Lett. 2011;205:S13–4.CrossRefGoogle Scholar
  4. 4.
    Brent J. Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009;360(21):2216–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Druteika DP, Zed PJ, Ensom MH. Role of fomepizole in the management of ethylene glycol toxicity. Pharmacotherapy. 2002;22(3):365–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Barceloux DG, Krenzelok EP, Olson K, Watson W. American academy of clinical toxicology practice guidelines on the treatment of ethylene glycol poisoning. Clin Toxicol. 1999;37(5):537–60.Google Scholar
  7. 7.
    Porter WH, Rutter PW, Bush BA, Pappas AA, Dunnington JE. Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol. 2001;39(6):607–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Mycyk MB, Wills B, Mazor S, Deslauriers C, Metz J. Fomepizole use is often suboptimal in cases of toxic alcohol poisoning. Ann Emerg Med. 2004;44(4):S89.CrossRefGoogle Scholar
  9. 9.
    Khajuria A, Krahn J. Osmolality revisited: deriving and validating the best formula for calculated osmolality. Clin Biochem. 2005;38(6):514–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Catchings T, Beamer W, Lundy L, et al. Adult respiratory distress syndrome secondary to ethylene glycol ingestion. Ann Emerg Med. 1985;14:594–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Krasowski MD, Wilcoxon RM, Miron J. A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps. BMC Clin Pathol. 2012;12(1):2–10.CrossRefGoogle Scholar
  12. 12.
    Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K, Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med. 1999;340(11):832–8.PubMedCrossRefGoogle Scholar
  13. 13.
    McStay CM, Gordon PE. Images in clinical medicine: urine fluorescence in ethylene glycol poisoning. N Engl J Med. 2007;356(6):611.PubMedCrossRefGoogle Scholar
  14. 14.
    Hauvik LE, Varghese M, Nielsen EW. Lactate gap: a diagnostic support in severe metabolic acidosis of unknown origin. Case Rep Med. 2018;2018:5238240.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Sagar AS, Kimenez CA, McKelvy BJ. Lactate gap as a tool in identifying ethylene glycol poisoning. BMJ Case Rep. 2018;2018:bcr-2018-224243. Scholar
  16. 16.
    Velez LI, Shepard G, Lee YC, Keyes DC. Ethylene glycol ingestions treated only with fomepizole. J Med Toxicol. 2007;3(3):125–8.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Hall TL. Fomepizole in the treatment of ethylene glycol poisoning. CJEM. 2002;4(3):199–204.PubMedCrossRefGoogle Scholar
  18. 18.
    Peterson CD, Collins AJ, Himes JM, Bullock ML, Keane WF. Ethylene glycol poisoning: pharmacokinetics during therapy with ethanol and hemodialysis. N Engl J Med. 1981;304(1):21–3.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Howland MS. Antidotes in depth: fomepizole. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE, editors. Goldfrank’s toxicologic emergencies. New York: McGraw-Hill; 2010.Google Scholar
  20. 20.
    Kostic MA, Dart RC. Rethinking the toxic methanol level. J Toxicol Clin Toxicol. 2003;41:793–800.PubMedCrossRefGoogle Scholar
  21. 21.
    Rehman H. Fomepizole for toxic alcohol poisoning. N Engl J Med. 2009;361(12):1213–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Ting SM, Ching I, Nair H, Langman G, Suresh V, Temple RM. Early and late presentations of ethylene glycol poisoning. Am J Kidney Dis. 2009;53(6):1091–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Wedge MK, Mataajan S, Johanson C, Patel R, Kanji S. The safety of ethanol infusions for the treatment of methanol or ethylene glycol intoxication: an observational study. CJEM. 2012;14(5):283–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Butler GK. When is it appropriate to treat ethylene glycol intoxication with fomepizole alone without hemodialysis? Semin Dial. 2011;24(4):441–2.CrossRefGoogle Scholar
  25. 25.
    Battistella M. Fomepizole as an antidote for ethylene glycol poisoning. Ann Pharmacother. 2002;36(6):1085–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Megarban B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005;31(2):189–95.CrossRefGoogle Scholar
  27. 27.
    Moreau CL, Kerns W II, Tomaszewski CA, McMartin KE, Rose SR, Ford MD, et al. Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. J Toxicol Clin Toxicol. 1998;36(7):659–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Buller GK, Moskowit CB, Eckardt K. The role of hemodialysis and fomepizole in ethylene glycol intoxication. J Nephrol Therapeutic. 2012;S10:4.Google Scholar
  29. 29.
    Beatty L, Green R, Magee K, Zed P. A systematic review of ethanol and fomepizole use in toxic alcohol ingestions. Emerg Med Int. 2013;2013:638057.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Watson WA. Ethylene glycol toxicity: closing in on rational, evidence-based treatment. Ann Emerg Med. 2000;36:139–41.PubMedCrossRefGoogle Scholar
  31. 31.
    Levine M, et al. Ethylene glycol elimination kinetics and outcomes in patients managed without hemodialysis. Ann Emerg Med. 2012;59(6):527.PubMedCrossRefGoogle Scholar
  32. 32.
    Borron SW, Megarbane B, Baud FJ. Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet. 1999;354:831.PubMedCrossRefGoogle Scholar
  33. 33.
    Caravati EM, Heileson HL, Jones M. Treatment of severe pediatric ethylene glycol intoxication without hemodialysis. J Toxicol Clin Toxicol. 2004;42(3):255–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415–46.PubMedCrossRefGoogle Scholar
  35. 35.
    Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005;12:78–85.PubMedCrossRefGoogle Scholar
  36. 36.
    Jammalamadaka D, Raissi S. Ethylene glycol, methanol, and isopropyl alcohol intoxication. Am J Med Sci. 2010;339(9):276–81.PubMedCrossRefGoogle Scholar
  37. 37.
    Bennett IL, Cary FH, Mitchell GL, Cooper MN. Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323 cases. Medicine. 1953;32(4):431–63.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Sharma R, Marasini S, Sharma A, Shrestha J, Nepal B. Methanol poisoning: ocular and neurological manifestations. Optom Vis Sci. 2012;89(2):178–82.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Zakharov S, Pelclova D, Diblik P, Urban P, Kuthan P, Nurieva O, et al. Lon-term visual damage after acute methanol poisonings: longitudinal cross-sectional study in 50 patients. Clin Toxicol. 2015;53(9):884–92.CrossRefGoogle Scholar
  40. 40.
    Noker P, Ells J, Tephly T. Methanol toxicity: treatment with folic acid and 5-formyl tetrahydrofolic acid. Alcohol Clin Exp Res. 2008;4(4):378–83.CrossRefGoogle Scholar
  41. 41.
    Roberts D, Yates C, Megarbane B, Winchester J, McClaren R, Gosselin S, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Extracorporeal Treatments in Poisoning Workgroup. Crit Care Med. 2015;43(2):461–72.PubMedCrossRefGoogle Scholar
  42. 42.
    Slaughter R, Mason R, Beasley D, Vale J, Schep L. Isopropanol poisoning. Clin Toxicol. 2014;52(5):470–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Emergency MedicineMichigan MedicineAnn ArborUSA

Personalised recommendations