What is the treatment for ethylene glycol ingestion?

Treatment for Ethylene Glycol Ingestion

Immediately initiate fomepizole upon suspicion of ethylene glycol poisoning based on clinical presentation (anion gap metabolic acidosis, elevated osmolar gap, or history of ingestion), and add hemodialysis for severe cases with significant acidosis (anion gap >27 mmol/L), acute kidney injury (Stage 2-3), or ethylene glycol levels ≥50 mg/dL. 1, 2

Immediate Antidote Therapy

Fomepizole (Preferred Agent)

• Administer fomepizole immediately upon suspicion without waiting for confirmatory ethylene glycol levels if patient presents with anion gap metabolic acidosis, increased osmolar gap, visual disturbances, oxalate crystals in urine, OR documented ethylene glycol concentration >20 mg/dL 1
• Loading dose: 15 mg/kg IV over 30 minutes, followed by 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol levels are undetectable or <20 mg/dL and patient is asymptomatic with normal pH 1
• Fomepizole blocks alcohol dehydrogenase, preventing formation of toxic metabolites (glycolic and oxalic acids) that cause metabolic acidosis, acute kidney injury, and death 1
• Critical advantage over ethanol: No CNS depression, no hypoglycemia, easier to maintain therapeutic levels, and superior outcomes in preventing treatment failure 3, 4

Ethanol (Alternative if Fomepizole Unavailable)

• Ethanol can be used as an alternative alcohol dehydrogenase inhibitor, but requires careful monitoring to maintain therapeutic levels 2
• Treatment failures are more common with ethanol monotherapy, particularly with very high ethylene glycol concentrations or when subtherapeutic ethanol levels occur 3

Extracorporeal Treatment (Hemodialysis) Indications

Strong Indications (Recommend ECTR)

Hemodialysis is lifesaving and strongly recommended when any of the following are present: 2

• Glycolate concentration >12 mmol/L (mortality increases substantially above this threshold) 2, 5
• Anion gap >27 mmol/L (with potassium; add 4 mmol/L if calculated without K+) 2, 5
• Coma or seizures due to ethylene glycol poisoning 2
• Stage 2 or 3 acute kidney injury (KDIGO criteria) 2
• Significant or worsening metabolic acidosis despite supportive care 1
• Ethylene glycol concentration ≥50 mg/dL when using fomepizole, or >50 mg/dL when using ethanol 2, 1

Suggested Indications (Consider ECTR)

• Glycolate concentration 8-12 mmol/L 2
• Anion gap 23-27 mmol/L 2
• Ethylene glycol concentration 20-50 mg/dL when using ethanol 2
• Osmol gap >50 when using ethanol 2

When ECTR May Be Avoided

• Fomepizole monotherapy without hemodialysis is safe and effective when anion gap <28 mmol/L (or <24 mmol/L for even greater safety margin), regardless of ethylene glycol concentration 3
• In early presentations with minimal acidemia and no acute kidney injury, fomepizole alone prevents progression to severe toxicity 3
• Do NOT initiate hemodialysis based solely on reported ingested dose without confirmatory laboratory evidence 2

Hemodialysis Technical Considerations

Modality and Timing

• Intermittent hemodialysis is the preferred modality (used in 86.5% of cases), with continuous kidney replacement therapy as an alternative 2
• Median time from admission to hemodialysis initiation is 6 hours 2
• Adjust fomepizole dosing during hemodialysis: Increase frequency to every 4 hours during dialysis (fomepizole is dialyzable) 1

Hemodialysis Endpoints

• Continue hemodialysis until ethylene glycol concentration <50 mg/dL and metabolic abnormalities are corrected 1
• Dialyze to remove ethylene glycol, glycolate, and oxalate metabolites 2

Discontinuation of Treatment

Stop fomepizole when ALL of the following criteria are met: 1

• Ethylene glycol concentrations undetectable or <20 mg/dL
• Patient is asymptomatic
• Normal pH achieved

Supportive Care

Adjunctive Therapies

• Sodium bicarbonate for severe metabolic acidosis (used in 44% of cases) 2
• Thiamine and pyridoxine as cofactors to potentially enhance metabolism of toxic intermediates (though evidence is limited) 2
• Mechanical ventilation if respiratory failure develops (required in 35% of cases) 2
• Vasopressors for refractory hypotension 2

Monitoring Parameters

• Frequent monitoring of ethylene glycol and glycolate concentrations, anion gap, arterial blood gas, serum electrolytes, and renal function 1, 5
• Glycolate correlates better with acute kidney injury and mortality than ethylene glycol concentration itself 5
• Beware: Elevated glycolate can falsely elevate lactate measurements on some analyzers due to cross-reactivity 5

Common Pitfalls and Caveats

Diagnostic Challenges

• Delayed presentations may lack elevated osmolar gap as ethylene glycol is metabolized to toxic metabolites, making diagnosis more difficult 6
• Do not rely solely on history of ingested dose—confirm with laboratory evidence (anion gap, osmolar gap, ethylene glycol levels) 2
• Calcium oxalate crystals in urine are supportive but present in only a minority of cases 2

Treatment Errors

• Do NOT use polycarbonate syringes or needles when administering fomepizole—it can compromise syringe/needle integrity 1
• Do not delay fomepizole initiation while awaiting confirmatory ethylene glycol levels if clinical suspicion is high 1
• Ethanol monotherapy has higher failure rates; fomepizole is strongly preferred when available 3, 4

Prognostic Factors

• Overall mortality is 18.7%, with higher rates (20.4%) in late presentations with glycolate >12 mmol/L or anion gap >28 mmol/L 2
• Chronic kidney disease develops in 16.8% of survivors, with dialysis-dependent CKD in 2.9% 2, 7
• Central nervous system sequelae occur in 3.3% of survivors 2
• Long-term nephrology follow-up is essential as survivors remain at risk for progressive renal decline 7