What is the treatment for ethylene glycol poisoning?

Treatment for Ethylene Glycol Poisoning

Immediately administer fomepizole (15 mg/kg loading dose) upon suspicion of ethylene glycol poisoning, and initiate hemodialysis if the patient presents with severe metabolic acidosis (anion gap >27 mmol/L), coma, seizures, acute kidney injury (KDIGO stage 2 or 3), or ethylene glycol concentration ≥50 mg/dL. 1, 2, 3

Immediate Antidote Therapy

Fomepizole is the preferred alcohol dehydrogenase inhibitor and should be started immediately upon suspicion based on history, anion gap metabolic acidosis, elevated osmolar gap, visual disturbances, or oxalate crystals in urine. 3

Fomepizole Dosing Protocol:

• Loading dose: 15 mg/kg IV over 30 minutes 3
• Maintenance: 10 mg/kg IV every 12 hours for 4 doses 3
• Subsequent doses: 15 mg/kg IV every 12 hours until ethylene glycol <20 mg/dL and patient is asymptomatic with normal pH 3
• During hemodialysis: Increase frequency to every 4 hours (fomepizole is dialyzable) 2, 3

Ethanol as Alternative:

• Ethanol can be used if fomepizole is unavailable, but requires careful monitoring to maintain therapeutic levels (100-150 mg/dL) 2, 4
• Ethanol therapy is less predictable and carries risks of CNS depression, dysphoria, and treatment failure 1, 5
• Critical pitfall: Ethanol monotherapy failures have been documented even with minimal acidosis, likely due to subtherapeutic ethanol concentrations 6

Extracorporeal Treatment (Hemodialysis) Indications

Hemodialysis is strongly recommended when ANY of the following criteria are met: 1

Biochemical Criteria:

• Anion gap >27 mmol/L (strong recommendation) 1, 2
• Anion gap 23-27 mmol/L (conditional recommendation) 1
• Glycolate concentration >12 mmol/L (strong recommendation) 1, 2
• Glycolate concentration 8-12 mmol/L (conditional recommendation) 1
• Osmolar gap >50 when ethanol is used as antidote 1
• Osmolar gap >10 when no antidote is available 1

Ethylene Glycol Concentration Thresholds:

• ≥50 mg/dL (≥50 mmol/L or 310 mg/dL) with fomepizole (conditional recommendation) or ethanol (strong recommendation) 1, 3
• 20-50 mmol/L (124-310 mg/dL) when ethanol is used (conditional recommendation) 1
• >10 mmol/L (>62 mg/dL) when no antidote available (strong recommendation) 1

Clinical Criteria (Strong Recommendations):

• Coma 1, 2
• Seizures 1, 2
• Acute kidney injury (KDIGO stage 2 or 3) 1, 2
• Chronic kidney disease with eGFR <45 mL/min/1.73m² (conditional recommendation) 1
• Significant or worsening metabolic acidosis 2, 3

Important nuance: Recent systematic review data suggests that fomepizole monotherapy without hemodialysis is safe and effective when anion gap <28 mmol/L, regardless of ethylene glycol concentration. 6 However, the EXTRIP guidelines take a more conservative approach with lower thresholds, which should be followed in clinical practice. 1

Hemodialysis Technical Considerations

Modality Selection:

• Intermittent hemodialysis is the preferred modality (most efficient for removing ethylene glycol and metabolites, corrects acidemia faster) 1, 2
• Continuous kidney replacement therapy (CKRT) is the second-line option if intermittent hemodialysis unavailable or if patient has marked brain edema 1
• Optimize settings: higher blood flow, higher effluent production, filters with higher surface area 1

Cessation Criteria:

Stop hemodialysis when: 1

• Anion gap <18 mmol/L (strong recommendation) 1
• Ethylene glycol concentration <4 mmol/L (25 mg/dL) (conditional recommendation) 1
• Acid-base abnormalities corrected (conditional recommendation) 1

Supportive Care

Metabolic Acidosis Management:

• Sodium bicarbonate for severe metabolic acidosis 2
• Fluid therapy to maintain adequate hydration 3

Cofactor Supplementation:

• Thiamine and pyridoxine to enhance metabolism of toxic intermediates 2
• Calcium supplementation for hypocalcemia 3
• Potassium supplementation as needed 3

Organ Support:

• Mechanical ventilation if respiratory failure develops 2
• Vasopressors for refractory hypotension 2

Monitoring Requirements

Frequent laboratory monitoring is essential: 3

• Blood gases, pH, electrolytes (anion gap calculation) 3
• BUN, creatinine, urinalysis 3
• Ethylene glycol and glycolate concentrations (if available) 3
• Urinary oxalate crystals 3
• Hepatic enzymes and white blood cell counts (transient increases and eosinophilia can occur with fomepizole) 3
• Electrocardiography (acidosis and electrolyte imbalances affect cardiovascular system) 3

Critical Pitfalls to Avoid

Administration Errors:

• Never use polycarbonate syringes or needles when diluting or administering fomepizole (can compromise syringe/needle integrity) 3
• Never give fomepizole undiluted or by bolus injection (causes venous irritation and phlebosclerosis) 3
• Always administer fomepizole as slow IV infusion over 30 minutes 3

Diagnostic Pitfalls:

• Do not rely solely on reported ethylene glycol dose for treatment decisions 1
• Anion gap only predicts need for hemodialysis if high pre-test probability of ethylene glycol exposure exists 1
• Anion gap may overestimate glycolate (concomitant AKI, ketoacidosis) or underestimate it (hypoalbuminemia, lithium/barium co-ingestion) 1
• Ethylene glycol concentrations diminish as metabolites accumulate, so both parent compound and acid-base status must guide treatment 3

Treatment Failures:

• Ethanol monotherapy failures occur with subtherapeutic ethanol levels or very high ethylene glycol concentrations 6
• Monitor for alcohol withdrawal in patients with alcohol use disorder, especially during hemodialysis 1
• Watch for minor allergic reactions (mild rash, eosinophilia) with fomepizole 3

Prognostic Factors

• Overall mortality rate: 18.7% 2
• Higher mortality with late presentations, glycolate >12 mmol/L, or anion gap >28 mmol/L 2, 6
• Chronic kidney disease develops in 16.8% of survivors (dialysis-dependent CKD in 2.9%) 2
• Death and progression of acute kidney injury almost nonexistent when anion gap <24 mmol/L 6