What is the treatment for ethylene glycol toxicity?

Treatment of Ethylene Glycol Toxicity

Immediately initiate fomepizole (or ethanol if fomepizole unavailable) as soon as ethylene glycol poisoning is suspected, and add extracorporeal treatment (hemodialysis) for severe cases based on specific laboratory and clinical criteria. 1, 2

Immediate Antidotal Therapy

Fomepizole is the preferred alcohol dehydrogenase inhibitor and should be started immediately upon suspicion of ethylene glycol ingestion based on patient history, anion gap metabolic acidosis, increased osmolar gap, visual disturbances, oxalate crystals in urine, OR documented serum ethylene glycol concentration >20 mg/dL. 2

Fomepizole Dosing (Without Hemodialysis)

• Loading dose: 15 mg/kg IV over 30 minutes 2
• Maintenance: 10 mg/kg IV every 12 hours for 4 doses 2
• Then: 15 mg/kg IV every 12 hours until ethylene glycol <20 mg/dL and patient is asymptomatic with normal pH 2
• Critical: Administer as slow IV infusion over 30 minutes—never give undiluted or as bolus injection due to risk of venous irritation and phlebosclerosis 2
• Important: Do not use polycarbonate syringes or needles, as fomepizole interacts with polycarbonate and compromises syringe integrity 2

Fomepizole Dosing During Hemodialysis

Fomepizole is dialyzable and requires increased dosing frequency: 2

• During hemodialysis: Dose every 4 hours (instead of every 12 hours) 2
• At hemodialysis initiation: If <6 hours since last dose, do not give additional dose; if >6 hours since last dose, give next scheduled dose 2
• At hemodialysis completion:
  • If <1 hour since last dose: no additional dose 2
  • If 1-3 hours since last dose: give half of next scheduled dose 2
  • If >3 hours since last dose: give full next scheduled dose 2
• After hemodialysis: Resume 12-hour dosing interval 2

Ethanol as Alternative

If fomepizole is unavailable, ethanol can be used as an alternative alcohol dehydrogenase inhibitor, though it causes CNS depression, hypoglycemia, and is more difficult to maintain at therapeutic levels. 2, 3 Note that ethanol decreases fomepizole elimination by approximately 50% if used concomitantly. 2

Extracorporeal Treatment (ECTR) Indications

Hemodialysis is the preferred ECTR modality over continuous kidney replacement therapy or hemoperfusion. 1, 4 Each indication below is independent—meeting any single criterion warrants ECTR. 1

Absolute Indications (Strong Recommendations)

• Coma: Recommend ECTR in any patient with coma due to ethylene glycol poisoning 1
• Seizures: Recommend ECTR in patients presenting with seizures from ethylene glycol poisoning 1
• Metabolic acidosis: Recommend ECTR if pH ≤7.25 1
• Acute kidney injury: Recommend ECTR with AKI Stage 2 or 3 (creatinine ≥2x baseline or urine output <0.5 mL/kg/hr for ≥12 hours) 1
• Glycolate concentration: Recommend ECTR if glycolate >12 mmol/L 1, 4
• Anion gap: Recommend ECTR if anion gap (Na + K - Cl - HCO3) >27 mmol/L 1, 4, 5

Plasma Ethylene Glycol Concentration-Based Indications

The threshold varies based on antidote availability: 1

When fomepizole is used:

• Suggest ECTR if ethylene glycol >50 mmol/L (>310 mg/dL) 1

When ethanol is used:

• Recommend ECTR if ethylene glycol >50 mmol/L (>310 mg/dL) 1
• Suggest ECTR if ethylene glycol 20-50 mmol/L (124-310 mg/dL) 1

When no antidote is available:

• Recommend ECTR if ethylene glycol >10 mmol/L (>62 mg/dL) 1

Osmolar Gap-Based Indications (When Evidence of Ethylene Glycol Exposure Exists)

When fomepizole is used:

• Suggest ECTR if osmolar gap >50 1

When ethanol is used:

• Recommend ECTR if osmolar gap >50 1
• Suggest ECTR if osmolar gap 20-50 1

When no antidote is available:

• Recommend ECTR if osmolar gap >10 1

Additional ECTR Indications

• Suggest ECTR if glycolate concentration 8-12 mmol/L 1
• Suggest ECTR if anion gap 23-27 mmol/L 1
• Recommend ECTR for renal failure, significant or worsening metabolic acidosis, or measured ethylene glycol ≥50 mg/dL 2

What NOT to Use as Sole Indication

Do not initiate ECTR based solely on reported ingested dose, as this may be imprecise and requires confirmation from laboratory findings. 1 Similarly, oxalate crystals in urine, urine immunofluorescence, or hypocalcemia alone are not indications for ECTR but may help diagnose poisoning. 1

ECTR Cessation Criteria

Continue ECTR until ALL of the following are met: 1, 4

• Ethylene glycol concentration <4 mmol/L (undetectable or <20 mg/dL) 1, 2
• Anion gap <18 mmol/L 1, 4
• Patient is asymptomatic with normal pH 1, 2
• All acid-base abnormalities are reversed 1, 4

Supportive Care and Monitoring

Essential Laboratory Monitoring

• Frequent measurements: Blood gases, pH, electrolytes, BUN, creatinine, urinalysis 2
• Ethylene glycol-specific: Serum ethylene glycol concentrations, urinary oxalate crystals 2
• Glycolate monitoring: Glycolate concentration correlates better with acute kidney injury and mortality than ethylene glycol itself 5
• Hepatic enzymes and white blood cell counts: Monitor for transient transaminase elevations and eosinophilia with repeated fomepizole dosing 2
• Electrocardiography: Perform due to effects of acidosis and electrolyte imbalances on cardiovascular system 2

Metabolic Management

• Sodium bicarbonate: Administer for metabolic acidosis correction 2, 6
• Electrolyte supplementation: Potassium and calcium supplementation usually necessary 2
• Oxygen administration: Typically required 2
• Adjunctive vitamins: Consider thiamine and pyridoxine as adjuvant therapy 4

Critical Pitfall: Lactate Measurement Interference

Be aware that elevated glycolate can falsely elevate lactate measurements on some analyzers due to cross-reactivity, potentially masking the true severity of toxic alcohol poisoning. 5 This can lead to underestimation of poisoning severity if relying solely on lactate values.

Special Considerations

Alcohol Withdrawal Risk

Patients with concomitant alcohol use disorder are at risk for alcohol withdrawal, especially if ECTR is performed. 1, 4 Implement usual withdrawal prophylaxis measures.

Anticoagulation During ECTR

While cerebral hemorrhage is uncommon in ethylene glycol poisoning (unlike methanol), it occasionally occurs. 1 The decision to anticoagulate the ECTR circuit should be made on a case-by-case basis considering bleeding risk.

Concomitant Ethanol Ingestion

Ethanol competes with ethylene glycol for alcohol dehydrogenase and can protect against toxic metabolite formation. 7 However, this does not eliminate the need for definitive treatment with fomepizole and ECTR when indicated.

Drug Interactions

Fomepizole may interact with drugs that induce or inhibit the cytochrome P450 system (phenytoin, carbamazepine, cimetidine, ketoconazole), though this has not been formally studied. 2 After 30-40 hours of treatment, fomepizole induces its own metabolism, significantly increasing elimination rate. 2

Decontamination

Do not perform gastrointestinal decontamination with ipecac syrup, gastric lavage, or activated charcoal—these are not effective for ethylene glycol and should not delay transportation to the emergency department. 8