Ethylene Glycol Toxicity

Etiology 

• Primary Source: Antifreeze and engine coolant containing ethylene glycol.

  • Commercial antifreeze preparations contain up to 95% ethylene glycol, often diluted 50/50 with water for use in automotive cooling systems.

  • A wide range of ready-to-use 50/50 prediluted ethylene glycol products are available for consumer convenience.

• Other Sources:

  • Heat-exchange fluids (solar heating systems, ice rink coolants)

  • Brake fluid, transmission fluid, and some industrial solvents.

• Pathophysiology:

  • Ethylene glycol’s sweet taste attracts dogs, cats, and wildlife, contributing to its risk.

  • Improper storage, disposal, or spillage exacerbates the likelihood of accidental exposure, particularly in colder climates during fall, winter, and spring months.

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Clinical Signs

• Initial Phase (30 mins – 12 hours post-ingestion):

  • Dogs & Cats: Neurologic signs resembling alcohol intoxication.

    • Ataxia, depression, stupor, knuckling, and decreased proprioception.

    • Vomiting, polydipsia, polyuria.

    • Possible brief clinical improvement (~12 hours post-ingestion).

• Progressive Phase (12–24 hours in cats; 36–72 hours in dogs):

  • Renal: Oliguric acute kidney injury (AKI) progressing to anuria.

    • Painful, enlarged kidneys upon palpation.

  • Gastrointestinal: Anorexia, vomiting, diarrhea, oral ulcers, hypersalivation.

  • Cardiopulmonary: Tachycardia, tachypnea, arrhythmias.

  • Central Nervous System: Lethargy, seizures, coma, death.

  • Dehydration: Due to kidney dysfunction and fluid loss.

• Other Species (Pigs, Poultry, Cattle):

  • Pigs: Depression, abdominal distension, muscle weakness, pulmonary edema.

  • Poultry: Ataxia, torticollis, respiratory distress, ruffled feathers.

  • Cattle: Depression, ataxia, hemoglobinuria (high doses), epistaxis, renal edema.

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Diagnosis

• History & Clinical Exam:

  • Document suspected exposure (e.g., access to antifreeze, recent vehicle maintenance, or presence of unsealed containers).

  • Clinical signs suggestive of intoxication (CNS depression, vomiting, and kidney dysfunction).

• Laboratory Diagnosis:

  • CBC & Biochemistry: Non-specific findings; often show azotemia, metabolic acidosis, and electrolyte disturbances.

  • Urinalysis: Characteristic findings include isosthenuria, acidic pH, and calcium oxalate crystals. Crystalluria can be detected as early as 3 hours post-ingestion (cats) and 6 hours (dogs).

  • Blood Gas Analysis: Often reveals metabolic acidosis with increased anion gap and elevated osmolar gap.

• Specific Tests:

  • Serum Ethylene Glycol Levels: Point-of-care, semiquantitative tests can detect levels as low as 20 mg/dL (cats) and 50 mg/dL (dogs) within the first 10–14 hours of ingestion.

  • Plasma Oxalate: Increased plasma oxalate concentration is correlated with a poorer prognosis and can assist in confirming the diagnosis 8–36 hours after ingestion.

  • Microscopic Examination of Urine: Monohydrate calcium oxalate crystals may appear as early as 3 hours (cats) or 6 hours (dogs) post-ingestion.

• Wood's Lamp: Some antifreeze formulations may fluoresce under UV light, although this is less commonly used in practice today.

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Treatment

• Initial Therapy:

  • Induction of Vomiting/Gastric Lavage: Consider if the ingestion occurred within 1–2 hours. Avoid in animals exhibiting severe CNS depression or neurologic signs due to aspiration risk.

  • Activated Charcoal: Not effective in ethylene glycol toxicosis, as the compound is absorbed rapidly from the GI tract.

• Supportive Care:

  • Intravenous Fluid Therapy: Essential for managing dehydration, correcting electrolyte imbalances, and increasing renal clearance of ethylene glycol. Fluid rate should be calculated based on body weight, dehydration percentage, and ongoing losses.

    • Fluid calculations:

      • Deficit Fluid Rate = Dehydration Deficit (mL/hr) + Ongoing Losses (mL/hr) + Maintenance Fluid Rate [(30 × kg body weight + 70) ÷ 24 hours].

    • Fluid replacement should correct dehydration over 8–12 hours.

• Specific Antidotes:

  • 4-Methylpyrazole (Fomepizole): Preferred in dogs; competitively inhibits alcohol dehydrogenase, the enzyme responsible for ethylene glycol metabolism.

    • Dogs: 20 mg/kg IV initially, then 15 mg/kg IV at 12 and 24 hours, and 5 mg/kg IV at 36 hours.

    • Cats (extra-label use): 125 mg/kg IV initially, followed by 31.3 mg/kg at 12, 24, and 36 hours.

  • Ethanol: If fomepizole is unavailable, ethanol is used as an alternative treatment. The regimen involves boluses or a constant-rate infusion depending on the animal's condition.

    • Dogs: 5.5 mL of 20% ethanol/kg body weight every 4 hours for five treatments, followed by every 6 hours for four more treatments.

    • Cats: 5 mL of 20% ethanol/kg body weight as a bolus, infused over 6 hours for five treatments, followed by 8-hour infusions for the next four treatments.

• Metabolic Support:

  • Sodium Bicarbonate: For correcting severe metabolic acidosis (pH <7.2, bicarbonate <12 mEq/L). Dose calculation: 0.3 − (0.5 × kg body weight) × (24 − plasma bicarbonate).

  • Calcium Gluconate: For hypocalcemia. Dosing varies by species (e.g., 10% calcium gluconate at 50–150 mg/kg for dogs, 94–140 mg/kg for cats).

  • Glucose: Supplemental dextrose (2.5–5%) to correct hypoglycemia.

• Continuous Monitoring:

  • Urine Output: Assess for oliguria or anuria. In oliguric or anuric cases, inhibition of alcohol dehydrogenase is unlikely to improve the outcome as most ethylene glycol has already been metabolized.

  • Electrolyte Levels: Monitor calcium and glucose levels closely, with ECG monitoring during calcium administration.

  • Renal Function: Monitor for signs of acute kidney injury, including ongoing azotemia and urine output changes.

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Prognosis

• Early Treatment:

  • If treated within the first 8 hours of ingestion, the prognosis improves significantly. Early recognition and antidote administration (fomepizole/ethanol) are critical for a favorable outcome.

• Late Stage/Severe Cases:

  • Prognosis becomes poorer if the animal presents with severe metabolic acidosis, significant renal damage (e.g., anuria, oliguria), or high levels of oxalate crystals in urine.

  • Animals in the later stages of toxicity with kidney failure and systemic involvement (pulmonary edema, gastrointestinal hemorrhage) may have a guarded to poor prognosis.

  • Chronic Kidney Disease: Survivors of severe poisoning may develop chronic kidney insufficiency, requiring long-term management.