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

  • Jędrzej Przystanowicz Department of Toxicology, Poznan University of Medical Sciences, Poland
  • Barbara Zielińska-Psuja Department of Toxicology, Poznan University of Medical Sciences, Poland
  • Joanna Kowalówka-Zawieja Department of Toxicology, Poznan University of Medical Sciences, Poland
  • Karina Sommerfeld Department of Toxicology, Poznan University of Medical Sciences, Poland
Keywords: ethylene glycol, fomepizole, acid-base balance, acute poisoning, rats

Abstract

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.

References

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.

Published
2016-02-17
How to Cite
Przystanowicz, J., Zielińska-Psuja, B., Kowalówka-Zawieja, J., & Sommerfeld, K. (2016). Acid-base balance in acute ethylene glycol poisoning in rats treated with fomepizole. Journal of Medical Science, 83(1), 29-36. Retrieved from http://jms.ump.edu.pl/index.php/JMS/article/view/40
Section
Original Papers