Skip to main content
SpringerLink
Log in

Current Management of Ethylene Glycol Poisoning

  • Therapy in Practice
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Ethylene glycol, a common antifreeze, coolant and industrial solvent, is responsible for many instances of accidental and intentional poisoning annually. Following ingestion, ethylene glycol is first hepatically metabolised to glycoaldehyde by alcohol dehydrogenase. Glycoaldehyde is then oxidised to glycolic acid, glyoxylic acid and finally oxalic acid. While ethylene glycol itself causes intoxication, the accumulation of toxic metabolites is responsible for the potentially fatal acidosis and renal failure, which characterises ethylene glycol poisoning.

Treatment of ethylene glycol poisoning consists of emergent stabilisation, correction of metabolic acidosis, inhibition of further metabolism and enhancing elimination of both unmetabolised parent compound and its metabolites. The prevention of ethylene glycol metabolism is accomplished by the use of antidotes that inhibit alcohol dehydrogenase. Historically, this has been done with intoxicating doses of ethanol. At a sufficiently high concentration, ethanol saturates alcohol dehydrogenase, preventing it from acting on ethylene glycol, thus allowing the latter to be excreted unchanged by the kidneys. However, ethanol therapy is complicated by its own inherent toxicity, and the need to carefully monitor serum ethanol concentrations and adjust the rate of administration.

A recent alternative to ethanol therapy is fomepizole, or 4-methylpyrazole. Like ethanol, fomepizole inhibits alcohol dehydrogenase; however it does so without producing serious adverse effects. Unlike ethanol, fomepizole is metabolised in a predictable manner, allowing for the use of a standard, validated administration regimen. Fomepizole therapy eliminates the need for the haemodialysis that is required in selected patients who are non-acidotic and have adequate renal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II

Similar content being viewed by others

References

  1. Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol 1997; 35(2): 127–43

    Article  PubMed  CAS  Google Scholar 

  2. Barceloux DG, Krenzelok EP, Olson K, et al. American Academy of Clinical Toxicology Practice Guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 1999; 37(5) 537–60

    Article  PubMed  CAS  Google Scholar 

  3. Budaveri S, editor. Merck Index 11th Edition. Rahway (NJ): Merck & Co, 1989

    Google Scholar 

  4. Litovitz TB, Klein-Schwartz W, Caravati EM, et al. 1998 Annual report of the American Association of Poison Control Centers. Am J Emerg Med 1999; 17(15) 435–87

    Article  PubMed  CAS  Google Scholar 

  5. Eder AF, McGrath CM, Dowdy YG, et al. Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis. Clin Chem 1998; 44: 168–77

    PubMed  CAS  Google Scholar 

  6. Clay KL, Murphy RC. On the metabolic acidosis of ethylene glycol intoxication. Toxicol Appl Pharmacol 1977; 39: 39–49

    Article  PubMed  CAS  Google Scholar 

  7. McChesney EW, Goldberg L, Parehk CK, et al. Reappraisal of the toxicology of ethylene glycol. II. Metabolism studies in laboratory animals. Food Cosmet Toxicol 1971; 9: 21–38

    Article  PubMed  CAS  Google Scholar 

  8. Peterson CD, Collins AJ, Himes JM, et al. Ethylene glycol poisoning: pharmacokinetics during therapy with ethanol and hemodialysis. N Engl J Med 1981; 304: 21–3

    Article  PubMed  CAS  Google Scholar 

  9. Mair W. Cerebral computed tomography of ethylene glycol intoxication. Neuroradiology 1983; 24: 175–7

    Google Scholar 

  10. Walder AD, Tyler CKG. Ethylene glycol antifreeze poisoning: three case reports and a review of treatment. Anaesthesia 1994; 49: 964–7

    Article  PubMed  CAS  Google Scholar 

  11. Gabow PA, Clay K, Sullivan JB, et al. Organic acids in ethylene glycol intoxication. Ann Intern Med 1986; 105: 16–20

    PubMed  CAS  Google Scholar 

  12. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med 1999; 340(11) 832–8

    Google Scholar 

  13. Introna Jr F, Smialek JE. Antifreeze (ethylene glycol) intoxications in Baltimore: report of six cases. Acta Morphol Hung 1989; 37: 245–63

    PubMed  Google Scholar 

  14. Berman LB, Schreiner GE, Feys J. The nephrotoxic lesion of ethylene glycol. Ann Intern Med 1957; 46: 611–9

    PubMed  CAS  Google Scholar 

  15. Milles G. Ethylene glycol poisoning with suggestions for its treatment as oxalate poisoning. Arch Pathol 1946; 41: 631–8

    CAS  Google Scholar 

  16. Bove KE. Ethylene glycol toxicity. Am J Clin Path 1966; 45: 46–50

    PubMed  CAS  Google Scholar 

  17. Aquino HC, Leonard CD. Ethylene glycol poisoning: report of three cases. J Ky Med Assoc 1972; 70: 463–5

    PubMed  CAS  Google Scholar 

  18. Gordon HL, Hunter JM. Ethylene glycol poisoning. Anaesthesia 1982; 37: 332–8

    Article  PubMed  CAS  Google Scholar 

  19. Kahn HS, Brotchner RJ. A recovery from ethylene glycol (antifreeze) intoxication: a case of survival and two fatalities from ethylene glycol including autopsy findings. Ann Intern Med 1950; 32: 284–94

    PubMed  CAS  Google Scholar 

  20. Bobbit WH, Williams RM, Freed CR. Severe ethylene glycol intoxication with multisystemic failure. West J Med 1986; 144: 225–8

    Google Scholar 

  21. Berger JR, Ayyar RA. Neurological complication of ethylene glycol intoxication: report of a case. Arch Neurol 1981; 38: 724–6

    Article  PubMed  CAS  Google Scholar 

  22. Spillane L, Roberts JR, Meyer AE. Multiple cranial nerve deficits after ethylene glycol poisoning. Ann Emerg Med 1991; 20: 208–10

    Article  PubMed  CAS  Google Scholar 

  23. Hoffman RS, Smilkstein MJ, Howland MA, et al. Osmol gaps revisited: normal values and limitations. J Toxicol Clin Toxicol 1993; 31(1): 81–93

    Article  PubMed  CAS  Google Scholar 

  24. Glaser DS. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med 1996; 27(3): 343–6

    Article  PubMed  CAS  Google Scholar 

  25. Jacobsen D, Akesson I, Shefter E. Urinary calcium oxalate monohydrate crystals in ethylene glycol poisoning. Scand J Clin Lab Invest 1982; 42: 231–4

    Article  PubMed  CAS  Google Scholar 

  26. Winter ML, Ellis MD, Snodgrass WR. Urine fluorescence using a Wood’s lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions. Ann Emerg Med 1990; 19: 663–7

    Article  PubMed  CAS  Google Scholar 

  27. Wallace K, Suchard J, Curry S, et al. Accuracy and reliability of urine fluorescence by Wood’s lamp examination for antifreeze ingestion. J Toxicol Clin Toxicol 1999; 37(5): 669

    Google Scholar 

  28. Vale JA. Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical toxicologists. J Toxicol Clin Toxicol 1997; 37(7): 711–9

    Google Scholar 

  29. Antizol® (fomepizole) injection. Product Monograph. Minnetonka (MN) 55305: Orphan Medical Inc., 1998

  30. Borron SW, Megarbane B, Baud FJ. Fomepizole in the treatment of uncomplicated ethylene glycol poisoning. Lancet 1999; 354(9181): 831

    Article  PubMed  CAS  Google Scholar 

  31. Baud FJ, Bismuth C, Garnier R, et al. 4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man. J Toxicol Clin Toxicol 1986–87; 26(6): 463–83

    Article  Google Scholar 

  32. Jacobsen D, Sebastian S, Blomstrand R, et al. 4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses. Alcohol Clin Exp Res 1988; 12(4): 516–22

    Article  PubMed  CAS  Google Scholar 

  33. Jacobsen D, Sebastian CS, Borron SK, et al. Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. J Emerg Med 1990 (8): 455–61

  34. Faessel H, Houze P, Baud FJ, et al. 4-Methylpyrazole monitoring during haemodialysis of ethylene glycol intoxicated patients. Eur J Clin Pharmacol 1995; 49: 211–3

    Article  PubMed  CAS  Google Scholar 

  35. Jobard E, Harry P, Turcant A, et al. 4-Methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol 1996; 34(4): 373–7

    Article  PubMed  CAS  Google Scholar 

  36. McMartin KE, Dies DF, Sebastian S, et al. Effects of intravenous 4-methylpyrazole in healthy human subjects. Vet Hum Toxicol 1989; 31(4): 365

    Google Scholar 

  37. Sivilotti MLA, Burns MJ, McMartin KE, et al. A model to predict ethylene glycol elimination during fomepizole monotherapy. J Toxicol Clin Toxicol 1999; 37(5): 669–70

    Google Scholar 

  38. Borron SW, Baud FJ, Garnier R. Intravenous 4-methypyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: a case report. Vet Hum Toxicol 1997; 39(1): 26–8

    PubMed  CAS  Google Scholar 

  39. Moreau C, Kerns W, Tomaszewski C, et al. Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. J Toxicol Clin Toxicol 1997; 35(5): 506

    Google Scholar 

  40. Cheng J-T, Beysolow TD, Kaul B, et al. Clearance of ethylene glycol by kidneys and hemodialysis. J Toxicol Clin Toxicol 1987; 25: 94–108

    Article  Google Scholar 

Download references

Acknowledgements

The author has accepted honoria for lecture engagements from Orphan Medical, Inc., the manufacturer and distributor of fomepizole (Amitol™) in the United States. He has no current financial relationship with Orphan Medical, Inc.

Author information

Authors and Affiliations

  1. Section of Clinical Pharmacology and Toxicology Associates, and Division of Emergency Medicine, University of Colorado Health Sciences Center, 2555 South Downing, Suite 260, Denver, Colarado, 80210, USA

    Jeffrey Brent

Authors
  1. Jeffrey Brent
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey Brent.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brent, J. Current Management of Ethylene Glycol Poisoning. Drugs 61, 979–988 (2001). https://doi.org/10.2165/00003495-200161070-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200161070-00006

Keywords

Search

Navigation