Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole

Jędrzej Przystanowicz, Barbara Zielińska-Psuja, Joanna Kowalówka-Zawieja, Karina Sommerfeld


Introduction. Ethylene glycol (EG) is relatively nontoxic but undergoes a multi-step oxidation to toxic metabolites, aldehydes and acids. The accumulation of organic acids, mainly glycolates, leads to the development of profound, life-threatening metabolic acidosis. A key therapy is an antidotal treatment with fomepizole (4-MP), the inhibitor of the first step of EG biotransformation enzyme, alcohol dehydrogenase.
Aim. The aim of the study was to demonstrate the efficacy of fomepizole in the prevention of acid-base balance disorders in acute ethylene glycol poisonings in rats.
Material and methods. Adult male Wistar rats were given EG (p.o.) with single (i.p.) or multiple (p.o.) doses of 4-MP (EG 3830 and 5745 mg/kg, respectively, 4-MP in single dose of 10 mg/kg or 15 mg/kg followed by 10 mg/kg every 12 hours). Blood gas analysis was performed and blood pH, bicarbonate concentration and base excess were evaluated.
Results and conclusions. The single dose of 4-MP was effective in preventing a decrease in blood pH, bicarbonate concentration and base excess during the entire experimental period (pH 7.35 vs 7.21 at hour 12, bicarbonate concentration 27.2 vs 18.3 mmol/dm3 at hour 8, base excess 1.8 vs -8.2 mmol/dm3 at hour 18). The multiple administration of 4‑MP started 2 hours after EG poisoning resulted in rapid restoration of proper values of acid- -base balance parameters. Fomepizole is highly efficacious in restraining the acid-base balance disorders which are concomitant with acute ethylene glycol poisonings.


ethylene glycol; fomepizole; acid-base balance; acute poisoning; rats

Full Text:



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

Brent J. Current management of ethylene glycol poisoning. Drugs. 2001;61(7):979–88.

Mégarbane B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005 Feb;31(2):189–95.

Puka J, Szajewski J. Ethylene glycol poisoning – an experience from treating 205 cases of acute poisoning (Polish). Pol Arch Med Wewn. 1988 Aug–Sep;80(2–3):88–98.

Clay KL, Murphy RC. On the metabolic acidosis of ethylene glycol intoxication. Toxicol Appl Pharmacol. 1977 Jan;39(1):39–49.

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

Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008 Jan;3(1):208–25.

Connally HE, Thrall MA, Hamar DW. Safety and efficacy of high-dose fomepizole compared with ethanol as therapy for ethylene glycol intoxication in cats. J Vet Emerg Crit Care. 2010 Apr 1;20(2):191–206.

Grauer GF, Thrall MA, Henre BA, Hjelle JJ. Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog. Toxicol Lett. 1987 Feb;35(2–3):307–14.

Olszowy Z. Experimental investigations on the course of ethylene glycol poisoning from a medico-legal and toxicological aspect. Part 2. Chosen biochemical parameters in experimental ethylene glycol poisoning (Polish). Arch Med Sąd Krym. 2000;50(2):89–101.

Giermaziak H, Lutz W, Giermaziak M. Biochemical and clinical aspects of the poisoning with ethylene glycol (Polish). Pol Tyg Lek. 1995;50(1–35):812–5.

Kujawa A, Kostek H, Szponar J, Majewska M, Ossowska B. Extremely severe metabolic acidosis and multi-organ complications in ethylene glycol intoxication: a case study (Polish). Przegl Lek. 2011;68(8):530–2.

Liamis G, Milionis HJ, Elisaf M. Pharmacologically-induced metabolic acidosis: a review. Drug Saf. 2010 May 1;33(5):371–91.

Blakeley KR, Rinner SE, Knochel JP. Survival of ethylene glycol poisoning with profound acidemia. N Engl J Med. 1993 Feb 18;328(7):515–6.

Kostek H, Kujawa A, Szponar J, Danielewicz P, Majewska M, Drelich G. Is it possible to survive metabolic acidosis with pH measure below 6.8? A study of two cases of inedible alcohol intoxication (Polish). Przegl Lek. 2011;68(8):518–20.

Bey TA, Walter FG, Gibly RL, James ST, Gharahbaghian L. Survival after ethylene glycol poisoning in a patient with an arterial pH of 6.58. Vet Hum Toxicol. 2002 Jun;44(3):167–8.

Guzek JW. Outline human pathophysiology (Polish). 1st ed. Warszawa: WL PZWL; 2002. p. 206–10.

Hewlett TP, Jacobsen D, Collins TD, McMartin KE. Ethylene glycol and glycolate kinetics in rats and dogs. Vet Hum Toxicol. 1989 Apr;31(2):116–20.

Carney E. An integrated perspective on developmental toxicity of ethylene glycol. Reprod Toxicol. 1994 Mar-Apr;8(2):99–113.

Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med. 1999 Mar 18;340(11):832–8.


  • There are currently no refbacks.

Copyright (c) 2016 Journal of Medical Science

Copyright 2018 by Journal of Medical Sciences