Thinking about getting your car winterized this fall? Antifreeze is 95% ethylene glycol, (an important chemical used to prevent your car’s radiator from freezing or your windshield from icing) which is toxic to most animals although dogs, and to a lesser extent cats, appear to be primarily affected. Improper storage and handling of this chemical often leads to poisoning of pets since it has a sweet taste that may be attractive to animals. Most poisonings are accidental, but unfortunately, malicious poisonings may also occur. There is a seasonal nature to the toxicity, with poisoning seen most commonly in the fall and winter when antifreeze is most commonly used.

The chemical formula for ethylene glycol is C2H6O2. It is a colorless and odorless liquid. Antifreeze poisoning is the second most common cause of fatal poisoning in animals according to the American Association of Poison Control Centers. Ethylene glycol is also present in hydraulic brake fluid, motor oil, inks, paints, and wood stains.

The mortality rate in dogs poisoned by antifreeze ranges from 50 to 70% and is thought to be even higher in cats. A relatively small dose of ethylene glycol is necessary to cause the death of a pet. The minimum lethal dose of ethylene glycol is 4.4 ml/kg in dogs and a mere 1.4 ml/kg in cats.

Antifreeze is quickly absorbed from the digestive tract with peak blood concentrations occurring within three hours of ingestion. Absorption may be delayed when food is in the stomach. Approximately 50% of the ingested ethylene glycol will be excreted unchanged by the kidneys. The other 50% of ingested ethylene glycol is metabolized by an enzyme called alcohol dehydrogenase (ADH) in the liver and to a much lesser extent in the kidneys, producing toxic metabolites which cause severe metabolic acidosis and kidney failure. Glycoaldehyde and glycolic acid are thought to be the metabolites primarily responsible for the toxicosis.

Clinical signs of antifreeze toxicity mimic those seen with marijuana, methanol, or ethanol (alcohol) intoxication. The patient will vomit due to GI irritation; they tend to have increased thirst and urination and may exhibit neurologic clinical signs. Neurologic signs are those attributed to the central nervous system, including depression, ataxia (unbalanced), stupor, and an inability of the pet to get up or right itself.

Clinical signs of acute kidney failure occur 12 to 24 hours following ingestion in cats and 36 to 72 hours in dogs. These animals will no longer urinate because they are unable to manufacture urine. They will be lethargic, anorexic, and dehydrated, develop oral ulcers, salivate, and possibly have seizures until becoming comatose. Urine production gradually decreases until no urine is being produced. The kidneys are often swollen and painful.

Hyperphosphatemia (high phosphorous levels in the blood) may be seen within 3 hours of ingestion. Commercial test kits may detect serum concentrations of ethylene glycol 1 to 2 hours after ingestion. Kidney markers BUN and creatinine begin to increase 12 hours after the ingestion of ethylene glycol. Hyperkalemia (high blood potassium levels) corresponds with the decrease in urine production. Approximately 50% of affected patients will have low levels of blood calcium and increased levels of serum glucose.

The prognosis depends upon the dose of ethylene glycol originally received by the patient and the time lapse between ingestion and the administration of treatment. In dogs, the prognosis is good when the toxicosis is recognized and treated within five hours following ingestion. This period is shorter in the cat, with treatment needing to be instituted within three hours of ingestion for the prognosis to be good.

An ethylene glycol toxicosis may be recognized by the development of calcium oxalate crystals in the urine 3 to 6 hours after ingestion in the cat and dog, respectively. These crystals appear as a clear six-sided prism. The blood or urine may also be tested for the presence of ethylene glycol. Serum concentrations of ethylene glycol peak 1 to 6 hours after ingestion and will no longer be detected after 48 to 72 hours. Serum osmolality may be measured one hour after ingestion for the detection of ethylene glycol and will remain high for up to 18 hours after ingestion. Many antifreeze solutions today contain sodium fluorescein, a florescent dye that aids in the detection of leaks in automotive coolant systems. A Wood’s lamp or black light may be used to detect fluorescence from the fluorescein stain in the oral cavity, face, vomit, urine, and coat. The dye is excreted up to six hours following ingestion of ethylene glycol in the urine.

Treatment is aimed at decreasing absorption of ethylene glycol by using an ADH inhibitor or a competitive substrate to the ethylene glycol. The affected pet is typically induced to vomit followed by the administration of activated charcoal to prevent further absorption of the ethylene glycol. These steps are helpful when the poisoning is caught 1-2 hours after ingestion. Once absorption has occurred, fomepizole (4- Methyl-1H-pyrazole) has become the preferred antidote in dogs, and more recently in cats. Fomepizole is an inhibitor of ADH enzyme used to metabolize ethylene glycol to its more toxic metabolites. By effectively preventing the activity of ADH, fomepizole causes 90% of the ethylene glycol to be excreted in the urine unmetabolized when treatment is begun three hours or less following ingestion. The administration of ethanol as a competitive substrate to the ethylene glycol is another commonly used treatment, with 80% of the ethylene glycol being excreted unmetabolized when treatment was begun in the same time frame. Ethanol-treated dogs will be depressed and recumbent for 36 to 72 hours, while the fomepizole-treated dogs will be clinically normal 24 hours after treatment.

Fomepizole is less effective in the cat than in the dog, necessitating higher doses and an increased incidence of side effects. Until recently, ethanol was the treatment of choice in the cat and some veterinarians may still prefer its use. The metabolic acidosis may be corrected by the administration of sodium bicarbonate.

The metabolism of glyoxylic acid to nontoxic end products may be enhanced by the use of thiamine and pyridoxine. Fluid therapy is used to correct the dehydration and promote kidney diuresis.

In pets where oliguric acute renal failure (urine is no longer being produced) is already present, the administration of fomepizole or alcohol is of little benefit and the prognosis is poor. Renal tubular damage may be reversible, but recovery may take weeks to months of intensive treatment. Peritoneal or hemodialysis may be helpful. Renal transplantation has had a variable success rate and central nervous system disorders such as seizures are a common and often fatal complication of severe cases.

Antifreeze poisoning may be prevented by making sure products containing ethylene glycol are stored out of the reach of pets in adequately sealed, preferably child-proof containers, and when product is replaced, it is disposed of properly. This toxicosis is much easier and cheaper to prevent than it is to cure.


References:

Gupta, Ramesh. Veterinary Toxicology. Elsevier. Amsterdam 2007. p.605.

Kahn, Cynthia Editor. The Merck Veterinary Manual. 9th Edition. 2005. Pp. 2357-2359.

Macintire, Douglass DVM, and Kenneth Drobatz DVM. Manual of Small Animal Emergency and Critical Care Medicine. Lippincott Williams & Wilkins. P. 398-401.

Peterson, Michael DVM and Patricia Talcott DVM. Small Animal Toxicology. Saunders Co. Pp. 702-726.