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Antifreeze Toxicoses

Jill A. Richardson, DVM
ASPCA Animal Poison Control Center

http://www.apcc.aspca.org

Methanol

Methanol (also known as methyl alcohol or wood alcohol) is found most commonly in "antifreeze" windshield washer fluid and varies in concentration from 20-100% (with 20-30% being the most common form.) Methanol's metabolite, formaldehyde, is rapidly oxidized by aldehyde dehydrogenase to formic acid, which can cause metabolic acidosis if significant quantities are ingested and retinal toxicity in humans and non-human primates. In general, alcohols are rapidly absorbed from gastrointestinal tract. The minimum toxic dose in dogs is 8.0 g/kg (or 3 ounces of 100% methanol). According to the ASPCA Animal Poison Control Center database, the most common exposures occur with dogs and usually involve chewing on containers or lapping up spills. With small exposures in dogs and cats, only mild gastric upset is seen. Recent small ingestion is treated with dilution (milk and water) that may help minimize gastric upset. Large exposure would be expected to only occur when there is no other water source available. In the case of a large ingestion, the animal should be monitored and treated for acidosis.

Propylene Glycol

Propylene glycol is the main ingredient in "safer" forms of engine antifreeze/ coolants. Prestone's Low Tox® and Sierra ® are two commercial forms of propylene glycol antifreeze available in the US. Propylene glycol is approximately 3 times less toxic in dogs than ethylene glycol. The oral LD50 of PG in dogs is 22g/kg and according to a study, no clinical signs were seen when a dog was given an acute dose of 20 ml/kg.

Propylene glycol is metabolized to lactate. In toxic quantities, acidosis, liver damage, and renal insufficiency are possible. Clinical signs of a propylene glycol toxicoses include CNS depression, weakness, ataxia, and seizures. With large ingestion, diuresis and supportive care, such as treatment for acidosis, should be given. The usefulness of 4MP (Fomepizole) for treating PG toxicosis is not known and treatment with ethanol may cause more problems in relation to the development of acidosis.

Ethylene Glycol

Ethylene glycol is the most dangerous form of antifreeze. Most commercial antifreeze products contain between 95-97% ethylene glycol. The minimum lethal dose of undiluted ethylene glycol antifreeze is 4.4-6.6ml/kg in dogs and 1.4ml/kg in cats. EG can cause metabolic acidosis and acute renal tubular necrosis. In most cases of ethylene glycol poisonings, vomiting is seen within the first few hours and then within 1-6 hours signs of depression, ataxia, weakness, tachypnea, polyuria, and polydipsia occur. By 18-36 hours acute renal failure occurs.

Peak levels of ethylene glycol are reached within 1-4 hours post ingestion. There is one commercial EG kit available for veterinary use (EGT Kit- PRN Pharmacal 1-800-874-9764) The approximate cost of the kit is $10 per kit and has a shelf life of 2 years. Ethylene glycol tests can be ran as early as 30 minutes post ingestion up to 12 hours. The EGT kit is labeled for dogs and detects a level greater than 50 mg/dl. Since cats are more sensitive than dogs, the kit may not be sensitive enough to diagnose a toxicosis in the cat. Some human labs may run a quantitative EG analysis to detect levels and could be considered with feline exposures. False positive test results can occur from propylene glycol (in some types of activated charcoal solutions and also from some injection solutions such as pentobarbital and diazepam) or from formaldehyde.

Induction of emesis is only helpful with recent exposures (<1 hour.) To prevent false positive EG tests, it is recommended to take a blood sample before administering activated charcoal since many products contain propylene glycol as inactive ingredients. Although its effectiveness is controversial, activated charcoal can be given within 1-3 hours of ingestion. Gastric lavage with activated charcoal could be considered but would only be effective early.

Ethylene glycol is metabolized via alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic acid, which is then metabolized to glyoxylic acid. Glycoaldehyde is more toxic than ethylene glycol. The formation of glycolic acid is thought to be responsible for causing metabolic acidosis. The goal of treatment of EG toxicoses is to slow down the metabolism.

Fomepizole (Antizole Vet tm by Orphan Medical --1-888-8-ORPHAN) is used to inhibit alcohol dehydrogenase and is considered the preferred treatment for treating EG toxicoses in dogs. One vial of fomepizole will treat a 60 lbs dog and cost about $240 per vial. Fomepizole does not cause hyperosmolality, metabolic acidosis, and CNS depression like ethanol treatment can. Fomepizole is given to dogs IV over a 36-hour period. The initial dose is 20 mg/kg (slow IV over 15-30 minutes), then 15mg/kg (slow IV) at 12 and 24 hours, and then 5mg/kg is given at 36 hours. Fomepizole is not effective in cats.

Ethanol also competes with ethylene glycol as a substrate for alcohol dehydrogenase, however it does have several unfavorable side effects, which include CNS depression, hyperosmolality, and metabolic acidosis. Ethanol can be used in cats and dogs. The preferred treatment regime would be to administer 8.6 mg/kg of a 7% ethanol solution and then maintain at 100 mg/kg/hour, up to 200 mg/kg/hr as a constant rate infusion. The other method of ethylene glycol treatment would be to make a 20% ethanol solution. Dogs are given 5.5 ml/kg every 4 hours for 5 treatments then every 6 hours for 4 treatments. Cats are given 5.0 ml/kg every 6 hours for 5 treatments, then every 8 hours for 4 treatments.

Fluid diuresis and correction of acidosis with sodium bicarbonate is also an important part of therapy. Peritoneal dialysis should be considered with anuric animals. Prognosis is good with early aggressive treatment (<8 hours of ingestion.)


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