What is the treatment for a patient with suspected ethylene glycol (antifreeze) intoxication?

Treatment of Ethylene Glycol Intoxication

Immediately administer fomepizole 15 mg/kg IV loading dose upon suspicion of ethylene glycol poisoning, before laboratory confirmation, 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

Immediate Antidote Therapy

• Start fomepizole immediately based on clinical suspicion alone—do not wait for laboratory confirmation if the patient has history of antifreeze ingestion, anion gap metabolic acidosis, increased osmol gap, visual disturbances, or oxalate crystals in urine. 2

• The loading dose is 15 mg/kg IV, followed by 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol concentration is <20 mg/dL and the patient is asymptomatic with normal pH. 2

• Administer fomepizole as a slow IV infusion over 30 minutes in at least 100 mL of sterile 0.9% sodium chloride or dextrose 5%. 2

• Critical warning: Do not use polycarbonate syringes or needles when diluting or administering fomepizole, as it can interact with polycarbonate and compromise syringe/needle integrity. 2

• If fomepizole is unavailable, ethanol can be used as an alternative (target serum level 100-150 mg/dL), but this requires intensive monitoring and has significant drawbacks including CNS depression and unpredictable alcohol dehydrogenase blockade. 1

Hemodialysis Indications (Strong Recommendations)

Initiate hemodialysis immediately if ANY of the following criteria are met:

• Anion gap >27 mmol/L (calculated as Na+ + K - Cl - HCO3-) 3, 1
• Coma 3, 1
• Seizures 3, 1
• Acute kidney injury (KDIGO stage 2 or 3) 3, 1
• Ethylene glycol concentration ≥50 mg/dL (≥50 mmol/L or 310 mg/dL) when using fomepizole 3, 1
• Glycolate concentration >12 mmol/L 3, 1
• Significant or worsening metabolic acidosis despite supportive care 2

Hemodialysis Indications (Conditional Recommendations)

Consider hemodialysis if:

• Anion gap 23-27 mmol/L 3
• Glycolate concentration 8-12 mmol/L 3
• Osmol gap >50 when using fomepizole 3
• Chronic kidney disease with eGFR <45 mL/min/1.73m² 3, 1

Hemodialysis Technical Considerations

• Intermittent hemodialysis is the preferred modality over all other extracorporeal treatments for faster removal of ethylene glycol and metabolites. 3, 1

• Continuous kidney replacement therapy (CKRT) is second-line if intermittent hemodialysis is unavailable or if the patient has marked brain edema. 3, 1

• During hemodialysis, increase fomepizole dosing frequency to every 4 hours because fomepizole is dialyzable. 1, 2

• At the beginning of hemodialysis: if <6 hours since last fomepizole dose, do not administer; if >6 hours, give the next scheduled dose. 2

• At the end of hemodialysis: if <1 hour since last dose, do not administer; if 1-3 hours, give half the next scheduled dose; if >3 hours, give the full next scheduled dose. 2

Cessation of Treatment

Stop hemodialysis when:

• Anion gap is <18 mmol/L (strongest criterion) 3
• Ethylene glycol concentration is <4 mmol/L (25 mg/dL) 3
• Acid-base abnormalities are corrected 3

Discontinue fomepizole when:

• Ethylene glycol concentration is undetectable or <20 mg/dL AND the patient is asymptomatic with normal pH. 2

Critical Pitfalls to Avoid

• Do not rely solely on reported ethylene glycol dose for treatment decisions—the amount ingested does not reliably predict toxicity. 3, 1

• Do not delay fomepizole administration waiting for laboratory confirmation—early treatment prevents formation of toxic metabolites (glycolate, glyoxylate, oxalate) that cause renal injury and acidosis. 4, 5

• Ethylene glycol concentrations diminish as metabolites accumulate, so monitor both parent compound levels AND acid-base status (anion gap, arterial blood gases) to guide treatment. 2

• Anion gap may overestimate or underestimate glycolate levels, so use multiple parameters together rather than relying on a single value. 1

• Early presentation with normal renal function and treatment with fomepizole before acidosis develops can prevent the need for hemodialysis entirely, even with extremely high ethylene glycol levels (>700 mg/dL). 5, 6

• Patients with plasma glycolate concentrations >97.7 mg/dL (12.9 mmol/L) at presentation are at highest risk for renal injury regardless of initial ethylene glycol concentration. 4

Supportive Care

• Correct metabolic acidosis with sodium bicarbonate as needed. 1

• Administer thiamine and pyridoxine as cofactors to enhance metabolism of toxic intermediates. 1

• Monitor for hypocalcemia (from calcium oxalate crystal formation) and supplement calcium as needed. 2

• Provide mechanical ventilation if respiratory failure develops. 1

• Use vasopressors for refractory hypotension. 1

• Monitor for alcohol withdrawal in patients with alcohol use disorder, especially during hemodialysis. 1

Monitoring Parameters

• Frequent measurements of arterial blood gases, pH, serum electrolytes (anion gap), BUN, creatinine throughout treatment 2

• Serial ethylene glycol and glycolate concentrations 2

• Urinalysis for oxalate crystals 2

• Hepatic enzymes and white blood cell counts (transient transaminase elevations and eosinophilia can occur with fomepizole) 2

• Electrocardiography (acidosis and electrolyte imbalances affect cardiovascular system) 2