What is the appropriate management of suspected ethylene glycol poisoning?

Management of Ethylene Glycol Intoxication

Immediately administer fomepizole (15 mg/kg loading dose) upon suspicion of ethylene glycol poisoning, and initiate hemodialysis if the patient presents with anion gap >27 mmol/L, glycolate >12 mmol/L, ethylene glycol concentration ≥50 mg/dL, coma, seizures, or acute kidney injury. 1

Immediate Antidote Therapy

Fomepizole is the preferred first-line antidote over ethanol due to more predictable alcohol dehydrogenase inhibition, absence of CNS depression, and simpler dosing without requiring continuous monitoring. 1

• Loading dose: 15 mg/kg IV immediately upon suspicion 1
• Maintenance dosing: Every 12 hours during standard therapy 2
• During hemodialysis: Increase frequency to every 4 hours as fomepizole is dialyzable 1
• Continue until: Ethylene glycol concentration <20 mg/dL, patient asymptomatic, pH normalized, and anion gap <18 mmol/L 1

If fomepizole is unavailable, ethanol can be used as an alternative ADH inhibitor, but requires intensive monitoring to maintain therapeutic levels of 100-150 mg/dL. 3, 1

• Ethanol dosing during hemodialysis: Increase maintenance rate to 250-350 mg/kg/hour 1
• Monitor ethanol levels: Every 2-4 hours during extracorporeal treatment 1
• Critical caveat: Ethanol causes CNS depression, unpredictable ADH blockade, and treatment failures occur even with minimal acidosis, requiring lower thresholds for hemodialysis. 1

Indications for Hemodialysis

Intermittent hemodialysis is strongly recommended (not just suggested) when ANY of the following criteria are met: 4, 1

Strong Indications (Recommend Hemodialysis):

• Anion gap >27 mmol/L 4, 1
• Glycolate concentration >12 mmol/L 4, 1
• Ethylene glycol concentration ≥50 mg/dL (≥50 mmol/L) 4, 1
• Severe clinical features: Coma, seizures, or acute kidney injury (KDIGO stage 2 or 3) 4, 1

Conditional Indications (Suggest Hemodialysis):

• Anion gap 23-27 mmol/L 4
• Glycolate concentration 8-12 mmol/L 4
• Osmol gap >50 (especially if using ethanol as antidote) 4, 1

Important distinction: If ethanol is used instead of fomepizole, the threshold for hemodialysis is LOWER because of unpredictable ADH blockade and higher risk of treatment failure. 1

Hemodialysis Technical Specifications

Intermittent hemodialysis is the preferred modality over continuous kidney replacement therapy (CKRT) because it removes ethylene glycol and metabolites faster and corrects acidemia more rapidly. 1

• If intermittent hemodialysis unavailable: Use CKRT as second-line option 4, 1
• Exception for CKRT: Consider if patient has marked brain edema 1

Cessation Criteria for Hemodialysis:

Stop hemodialysis when ALL of the following are achieved: 4, 1

• Anion gap <18 mmol/L 4, 1
• Ethylene glycol concentration <4 mmol/L (25 mg/dL) 4, 1
• All acid-base abnormalities corrected 1

Supportive Care

• Sodium bicarbonate: For severe metabolic acidosis 1
• Thiamine and pyridoxine: As cofactors to enhance metabolism of toxic intermediates 1, 5
• Mechanical ventilation: If respiratory failure develops 1
• Vasopressors: For refractory hypotension 1

Critical Diagnostic Pitfalls to Avoid

Do not rely solely on reported ethylene glycol dose for treatment decisions because anion gap only predicts need for hemodialysis if high pre-test probability exists. 1

• Measure both parent compound AND metabolites: Ethylene glycol concentrations diminish as toxic metabolites (glycolate, oxalate) accumulate, so both must guide treatment 1
• Anion gap limitations: May overestimate or underestimate glycolate concentration 1
• Suspect ethylene glycol in: Intoxicated patient with anion gap acidosis, hypocalcemia, urinary crystals (calcium oxalate monohydrate), and nontoxic blood alcohol concentration 6
• Early neurological symptoms: Altered mental status, seizures, or coma may appear before significant acidosis develops 5

Special Considerations

Monitor for alcohol withdrawal in patients with alcohol use disorder, especially during hemodialysis when ethanol is being removed. 1, 5

Timing is critical: Initiating fomepizole before serum creatinine rises can minimize renal impairment, with metabolic acidosis resolving within 3 hours of therapy initiation. 6

Prognosis

• Overall mortality: 18.7% across all cases 1
• Mortality with glycolate ≤12 mmol/L or anion gap ≤28 mmol/L: 3.6% 4
• Chronic kidney disease in survivors: 16.8%, with dialysis-dependent CKD in 2.9% 1
• Higher mortality: Late presentations with glycolate >12 mmol/L or anion gap >28 mmol/L 1