What is the role of ethanol treatment in a patient with ethylene glycol intoxication, particularly when fomepizole is unavailable?

Ethanol Treatment for Ethylene Glycol Poisoning When Fomepizole is Unavailable

Ethanol is an effective alternative alcohol dehydrogenase inhibitor when fomepizole is unavailable, but requires more aggressive hemodialysis thresholds and intensive monitoring to maintain therapeutic blood levels of 100-150 mg/dL. 1

Ethanol Dosing Protocol

Loading and Maintenance Doses

• Loading dose: 10 mL/kg of 10% ethanol solution IV (or 0.8-1.0 g/kg) 1
• Maintenance dose: 1.4-2.0 mL/kg/hour of 10% ethanol solution to maintain blood ethanol levels of 100-150 mg/dL 1
• During hemodialysis: Increase maintenance rate dramatically to 250-350 mg/kg/hour because ethanol is highly dialyzable (elimination half-life during dialysis: 1.5-3.0 hours; clearance >100 mL/min) 1, 2

Critical Monitoring Requirements

• Monitor ethanol levels every 2-4 hours during treatment, especially during hemodialysis 1
• Adjust infusion rates based on measured ethanol concentrations to maintain therapeutic range 1
• Watch for CNS depression, dysphoria, and hypoglycemia as complications of ethanol therapy 3, 1

Lower Thresholds for Hemodialysis with Ethanol

When using ethanol instead of fomepizole, the EXTRIP workgroup recommends hemodialysis at lower ethylene glycol concentrations because ADH blockade with ethanol is unpredictable and treatment failures occur even with minimal acidosis. 1

Hemodialysis Indications with Ethanol (Stronger Recommendations)

• Ethylene glycol concentration >50 mmol/L (>310 mg/dL) OR osmol gap >50 - strongly recommend hemodialysis 1
• Ethylene glycol concentration 20-50 mmol/L (124-310 mg/dL) OR osmol gap 20-50 - suggest hemodialysis 1
• Anion gap >27 mmol/L - strongly recommend hemodialysis 3, 1
• Glycolate concentration >12 mmol/L - strongly recommend hemodialysis 3
• Severe clinical features: coma, seizures, or acute kidney injury (KDIGO stage 2 or 3) - strongly recommend hemodialysis 3, 1

Rationale for Lower Thresholds

The rationale for more aggressive hemodialysis when using ethanol is threefold: 1

• Ethanol provides less predictable ADH blockade compared to fomepizole
• Treatment failures documented even without significant acidosis at presentation
• Prolonged ethanol therapy (>48 hours often needed for high concentrations) carries substantial risks including CNS depression and requires high-dependency unit admission

Duration and Cessation Criteria

Continue Ethanol Until:

• Ethylene glycol concentration <4 mmol/L (25 mg/dL) 1
• Anion gap normalizes to <18 mmol/L 1
• Metabolic acidosis resolves 1

Stop Hemodialysis When:

• Anion gap <18 mmol/L 3
• Ethylene glycol concentration <4 mmol/L (25 mg/dL) 3
• All acid-base abnormalities are corrected 3

Critical Pitfalls to Avoid

Inadequate Ethanol Levels During Dialysis

• Most common error: Failing to increase ethanol infusion rate during hemodialysis leads to breakthrough metabolism of ethylene glycol 1, 2
• Both fomepizole and ethanol are readily dialyzable and require increased dosing during extracorporeal treatment 3

Alcohol Withdrawal Risk

• Patients with concomitant alcohol use disorder are at high risk for withdrawal, especially during hemodialysis 3
• Implement usual withdrawal prophylaxis measures (benzodiazepines) proactively 3

Delayed Treatment Decisions

• With ethylene glycol concentration >50 mmol/L and ethanol therapy (T1/2 = 14 hours), treatment would require >48 hours before reaching safe concentrations, during which risks of ethanol side effects and therapeutic failure become considerable 3
• This prolonged exposure justifies lower thresholds for hemodialysis when using ethanol versus fomepizole 3

Comparison to Fomepizole

While ethanol remains an effective alternative, fomepizole is preferred when available because it provides more predictable ADH inhibition without CNS depression, requires no level monitoring, and allows higher thresholds before hemodialysis is needed. 1, 4, 5, 6

The key difference: fomepizole allows treatment of ethylene glycol concentrations up to 50 mg/dL without hemodialysis if renal function is intact and no acidosis develops, whereas ethanol requires hemodialysis at lower concentrations due to unpredictability 3, 1, 7, 5