Ethylene glycol (E.G.) is a sweet, colorless, odorless liquid that is very palatable to dogs, cats and other species. The primary source of ethylene glycol is from antifreeze used in car engines and sometimes in toilets to prevent freezing. Antifreeze contains  95-98% E.G..  Ethylene glycol is also used as an industrial solvent, used in color film processing (diethylene glycol), and some windshield cleaning solutions.

E.G. intoxication is most common in the fall when cars are "winterized" by draining the radiator and adding new antifreeze. Species vary in susceptibility. Species which are most susceptible (the undiluted lethal dose is in parentheses) include man (1.4 ml/Kg), monkey, and cats (1.5 ml/Kg).  Species of intermediate susceptibility include rats and dogs (4.2 - 6.6 ml/Kg). The most resistant species are mice, guinea pigs, rabbits, and poultry (7 - 8 ml/Kg). Despite species differences, most animals find the chemical to be palatable and will consume large quantities, if available.

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Metabolism of E.G.: E.G. is rapidly absorbed from the gastrointestinal tract and is distributed to all tissues. Metabolism takes place primarily in liver and to a lesser degree, in the kidneys. Ethylene glycol is converted to glycolaldehyde by alcohol dehydrogenase (ADH). This is the rate limiting step in metabolism. Metabolism continues to  glycolate, then to glyoxylate, then to glycine and oxalate. The glycine is later converted to hippuric acid. Oxalate binds to calcium.

E.G. itself is not very toxic, most is excreted by the kidneys unchanged. The intermediate products are toxic. Only 0.25% - 2.5% of ingested E.G. is converted to oxalate. The half life of E.G. is 11 hours.

E.G. intoxication progresses through 3 stages . Stage 1 lasts 30 minutes to 12 hours. Signs include depression, vomiting, ataxia, seizures, polydipsia and polyuria, coma, and death. The CNS signs are due to CNS depression by glycolaldehyde and glycolic acid and to metabolic acidosis and hyperosmolality. E.G. with a molecular weight of 62 exerts a strong osmotic force as do all its metabolites which are also small molecules.

Stage 2 develops within 12-24 hours of ingestion. This stage is not well documented in dogs or cats. It is characterized in humans by cardiopulmonary signs including tachypnea, tachycardia, pulmonary edema, hyperemia, and congestion. The cardiopulmonary signs may be a sequel of the CNS depression of stage 1.

Stage 3 develops at ~ 24-72 hours following ingestion. Renal failure develops in stage 3. Signs include oliguria, azotemia/uremia, isosthenuria, vomiting, anorexia, depression, and renal pain. Renal damage is due to tubular damage induced by E.G. metabolites and impaired renal blood flow due to renal edema. Calcium oxalate crystal deposition in the renal tubules probably plays a minor role in the development of renal failure but does provide a diagnostic clue and causes hypocalcemia.

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Diagnosis: The history and clinical presentation often make one suspicious of a diagnosis of E.G. intoxication. Successful therapy hinges on a rapid diagnosis. The clinical findings may mimic other polysystemic diseases including ARF of another cause, acute gastroenteritis, pancreatitis, and diabetic ketoacidosis.

Lab findings include azotemia, hyperphosphatemia, hyperkalemia, severe hypocalcemia, metabolic acidosis, isosthenuria, acid urine and sometimes glucosuria or proteinuria. Blood calcium may be extremely low. Always consider antifreeze poisoning in azotemic patients with a marked reduction in calcium. 

Calcium oxalate crystals may be observed in urine within 3 hours of ingestion. They may be octahedral shaped (dihydrate) or spindle shaped (monohydrate).

dihydrate	monhydrate

Fine needle aspiration of the kidney can disclose crystals if they are not observed in urine. A single monohydrate calcium oxalate crystal is pictured at 2 magnifications.

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The kidneys may be enlarged and painful on palpation. Survey radiographs or ultrasound may also demonstrate enlarged kidneys.

Additional lab tests can be performed for diagnosis. E.G. blood and urine levels can be measured by some laboratories.

An easy to use kit is currently available to detect E.G. in blood.

PRN pharmacal Inc., 5830 McAllister Avenue, Pensacola, FL 32504

This kit is positive for 12 - 24 hours as it measures ethylene glycol but not its metabolites. A positive test result is pictured on the left.   False positives are unusual.

Osmol gap: As E.G. and its metabolites are small molecules they dramatically increase plasma osmolality. Normal plasma osmolality is 280-310 mOsm/Kg. Osmolality can be measured using an osmometer or calculated by adding the concentrations of small molecules which contribute to osmolality in health. Normally the difference between calculated and measured osmolality, which is called the osmol gap is less than 10 mOsm/Kg. E.G. intoxication may result in a gap of 60 mOsm/Kg or greater. An osmol gap exists as E.G. and metabolites are measured by an osmometer but are not taken into account in the formula which is used to calculate osmolality.

Example of a normal animal:

 if the measured osmolality is 287, the difference (289- 287) is not significant, an osmol gap is not present.

Ethylene glycol patient:

  if the measured osmolality is 550, the difference (550- 354 = 196) is an osmol gap and indicates the presence of an osmotically active molecule in the blood that is not taken into account in the calculated formula.

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The presence of an anion gap can also indicate ethylene glycol toxicity.

The amount of negatively charged anions is balanced by an equal amount of positively charged cations.  Sodium and potassium are the major cations which are measured. Bicarbonate and chloride are the major anions.

(Na + K) - (HCO₃ + Cl) is normally 15-25 mEq/L. The gap between major cations and anions is made up negatively charged proteins, phosphates and sulfates. The metabolites of E.G. are negatively charged and increase this gap to 40-50 mEq/L.

Example of anion gap:

Normal dog: (140 + 4) - (22 + 110) = 12

E.G. Patient: (140 + 8) - (10 + 98) = 40

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Treatment: Some of the recommended treatment measures for E.G. have their own inherent RISKS. It is important to monitor the patient for worsening of clinical signs that may be due to treatment.  Treatment includes:

Induce emesis if the animal is presented within hours of ingestion. If azotemia is already present, at least 24 hours have elapsed and the E.G. is already out of the gastrointestinal tract. After inducing vomiting administer activated charcoal to reduce absorption of E.G. that has left the stomach. Because the animal is depressed during the first stage of E.G. poisoning, they are at risk for aspiration.

Fluid therapy is indicated to correct dehydration and promote excretion of E.G. and its metabolites. If the animal is oliguric they are at risk for fluid overload. The fluid therapy protocol is the same as for ARF of other causes.

Ethanol competes with E.G. for the enzyme alcohol dehydrogenase (ADH) and decreases the amount of E.G. which is metabolized. Ethanol has a 7-10 fold greater affinity for ADH than does E.G.. The plasma half-life of E.G. in dogs is 11 hours. Therefore, the best results with ethanol occur when given within 1-2 hours of ingestion. The patients are already hyperosmolar and depressed. 20% ethanol has an osmolality of 3,429 mOsm/L. Ethanol will further increase osmolality and is a potent CNS depressant. The trade-off for inhibiting ADH is additional depression and worsening of the hyperosmolality. Ethanol is not indicated if greater than 24 hours have elapsed since ingestion.

Suggested doses of ethanol

• Dogs: 5.5 ml of 20% ethanol/Kg IV every 4 hours for 5 treatments then every 6 hours for 4 treatments
• Cats: 5.0 ml of 20% ethanol/Kg IP every 6 hours for 5 treatments then every 8 hours for 4 treatments

4-methylpyrazole is also an inhibitor of alcohol dehydrogenase. There are no toxic side effects in dogs at doses used and it does not contribute to CNS depression. 4-methylpyrazole is not indicated if greater than 24 hours elapsed since ingestion. 4 methylpyrazole is currently available through Orphan Medical Company as Antizol-Vet^TM (fomepizole) for injection.

Connally HE, Thrall MA, Abstract, Safety and Efficacy of High Dose Fomepizole as Therapy for E.G. Intoxication in Cats Proceedings, 8th IVECCS, San Antonio, TX, September, 2002

Cats were given 125 mg/kg 4-MP slow IV as a loading dose then 31.25 mg/kg @ 12, 24, 36 hours. In cats treated 3 hours or less after exposure this regiment was 100% effective based on recovery vs. 25% for ethanol treatment. However, at 4 hours post ethylene glycol ingestion, there was 100% mortality even with 4-MP.

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Large doses of sodium bicarbonate are recommended to combat the severe metabolic acidosis of E.G. poisoning. Recommendations range from (0.2 - 0.5) body weight (Kg) x bicarbonate deficit to be given every 4-6 hours with frequent acid-base determinations. Rapid correction of acidosis lowers the amount of ionized calcium which is already low from chelation with oxalate and may precipitate hypocalcemic tetany. Over alkalinization can also precipitate paradoxical CSF acidosis and associated neurologic signs.

Mannitol is recommended by some to produce an osmotic diuresis and decrease renal edema. Mannitol adds to hyperosmolality. Other diuretics or dopamine are preferred in oliguric patients.

Hemo and peritoneal dialysis removes E.G. and its metabolites as they are small molecules. Other substances which may be abnormal which can be removed by dialysis include urea nitrogen, creatinine, phosphorous, and potassium. Calcium and alkalizing agents can be added by dialysis.

The prognosis for E.G. patients is very poor. Clients should be educated to prevent exposure. Propylene glycol containing antifreeze (Sierra) is less toxic than ethylene glycol based antifreeze.

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In July 2006, a House panel approved a bill that would require antifreeze makers to add a bitter-tasting chemical to auto coolants, making them unpalatable to children and pets.

The Energy and Commerce Committee approved the bill (HR 2567) http://oesa.org/publications/articledetail.php?articleId=3980