Ethylene glycol poisoning

Ethylene glycol, whose IUPAC name is 1,2-ethandiol, belongs to the category of diols. At room temperature it is transparent liquid with a syrupy appearance and a sweetish taste.

Ethylene glycol is used in paints, inks, detergents, colour film developing fluids and in engine cooling fluids. Its sweetish taste makes it very palatable, explaining the frequency of poisoning by ingestion among domestic animals (usually dogs and cats).

METABOLISM

TOXICITY

Ethylene glycol is rapidly absorbed from the gastrointestinal tract (irritant effect), such that the peak plasma concentration in the dog occurs 3 hours after ingestion. Fifty percent of the ingested ethylene glycol is excreted unchanged though the kidneys.

Before being metabolised, ethylene glycol is no more toxic than ethanol, although it is in any case a strong central nervous system depressant. Its biotransformation into metabolites renders it more toxic, leading to metabolic acidosis and renal failure.

CLINICAL SIGNS

The clinical signs are dose- and time-dependent and their appearance can be divided into three phases.

First phase: from 30 minutes up to 12 hours after ingestion

• Gastrointestinal irritation
• Increased concentration in the blood
• Nausea, vomiting
• Central nervous system depression
• Polyuria (osmotic diuresis)
• Polydipsia (due to stimulation of the thirst centre). As central nervous system depression progresses, the animal drinks less, but the osmotic diuresis continues, leading to dehydration
• Ataxia
• Muscle fasciculation, staggering
• Possible convulsive crises

Second phase: if the animal survives the first phase, there is a slight improvement of signs, followed by cardiopulmonary effects, including:

• Tachypnoea
• Tachycardia, weak and fast pulse
• Metabolic acidosis

Third phase: from 24 to 72 hours after ingestion (although sometimes later)

• Anorexia, vomiting, diarrhoea
• Lethargy
• Dehydration 
• Foul breath (fetor uremicus)
• Convulsions (sometimes present)
• Depression, coma and, in the most severe cases, death.

The intoxication may not be fatal, particularly if a modest amount of poison has been ingested; nevertheless, the renal impairment is permanent and may be very harmful in elderly subjects.

Histopathological evidence of renal tubular necrosis, pulmonary oedema and gastrointestinal bleeding may be present.

LABORATORY ANALYSES

• Presence of acid metabolites in the serum (metabolic acidosis)
• Decreased concentration of bicarbonate in the plasma, already visible within 1 hour of ingestion of ethylene glycol
• Anion imbalance between 1-6 hours after intake of the ethylene glycol
• Increases in blood urea nitrogen (BUN) and creatinine in the blood. These increases generally occur 12 hours after intake in the cat and between 24 and 48 hours after ingestion in the dog
• Following renal damage: haematuria, proteinuria and glucosuria and lowering of the specific gravity of urine (< 1.020). Deposits of oxalate crystals [5],which appear birefringent under a polarised light, in the renal tubules.

DIAGNOSIS

When it is not known that ethylene glycol has been ingested, the diagnosis is based on the history, signs and results of laboratory examinations. Three hours after ingestion of toxic doses of ethylene glycol, dogs and cats develop a normochloraemic acidosis, with an increase in the anion gap, hypotonic, acid urine and serum hyperosmolality. Calcium oxalate crystals appear in the urine 3 hours after intake of ethylene glycol in the cat, and 6 hours in the dog.

Some antifreezes contain fluorescein, which appears yellow-green under the light of a Wood’s lamp; thus, fluorescence of the urine, used as an auxiliary test in human medicine, can also be used in veterinary medicine.

TREATMENT

In the case of recent ingestion (within 30 minutes), it can be useful to induce vomiting or administer activated charcoal to limit the absorption of the toxic product. Considering that ethylene glycol is absorbed quickly, an effective way to limit its metabolism is to administer fomepizole (4-methylpyrazole; 4-MP), an inhibitor of alcohol dehydrogenase which, unlike ethanol (used as an antidote in the past), does not cause depression of the central nervous system. The treatment of ethylene glycol intoxication comprises:

• Fomepizole. In dogs: 20 mg/kg i.v. as a loading dose and subsequent doses at 12 hours (15 mg/kg i.v.), 24 hours (15 mg/kg i.v.) and 36 hours (5 mg/kg, i.v.) after the initial dose. If no improvement is seen after the application of this protocol and it is certain that the animal has ingested ethylene glycol, the therapy must be continued at the dose of 5 mg/kg every 12 hours until the clinical conditions improve.
• In cats: 4-MP has not yet been studied thoroughly, so the advised treatment is a 20% solution of ethanol at a dose of 5 ml/kg, administered i.v., drop by drop, over 6 hours, for five treatments, then every 8 hours for four administrations.
• Sodium bicarbonate to correct the metabolic acidosis. The amount to administer is calculated on the basis of the bicarbonate deficit, using the following formula:

Bicarbonate deficit = 0.3 x body weight (kg) x (24-plasma bicarbonate)

Bicarbonate is administered by slow intravenous infusion; the bicarbonate levels should be measured every 4-6 hours and administration repeated as needed. In the case that it is not possible to measure the bicarbonate levels, an alternative protocol is recommended:

• dogs: 5% sodium bicarbonate: 8 ml/kg i.p. every 4 hours, five times, then every 6 hours, four times.
• cats: 5% sodium bicarbonate: 6 ml/kg i.p. every 6 hours, five times, then every 8 hours, four times.

Fluid therapy to correct the dehydration and facilitate elimination of the ethylene glycol.

PROGNOSIS

The prognosis depends on the speed with which the intoxication is identified and the therapy started. In dogs treated with 4-MT within 5 hours of ingestion of ethylene glycol, the prognosis is excellent; in cats, this outcome is obtained if treatment is started within 3 hours. If the intervention is delayed, the prognosis is poor, and the intoxication can be fatal.

Suggested readings

1. Connally HE, Hamar DW, Thrall MA. Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole. Am J Vet Res 2000 61:450-5.
2. Dial SM, Thrall MA, Hamar DW. Comparison of ethanol and 4-methylpyrazole as treatments for ethylene glycol intoxication in cats. Am J Vet Res 1994;55:1771-82.
3. Dial SM, Thrall MA, Hamar DW. Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs. Am J Vet Res 1994;55:1762-70.
4. Goicoa A, Barreiro A, Peña ML, et al. Atypical presentation of long-term ethylene glycol poisoning in a German shepherd dog. Vet Human Toxicol 2003;45:207-9.
5. Hess R, Bartels MJ, Pottenger LH. Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data. Arch Toxicol 2004;78:671-80.
6. http://www.vet.uga.edu/VPP/CLERK/Torres/index.php
7. Il Manuale Merck Veterinario. 8^th edn. Giraldi editore.
8. Veterinary Toxicology, Basic and Clinical Principles. Gupta RC (ed).