A 28-year-old woman is admitted to the ICU 8 hours after consuming approximately 150 mL of bootleg whiskey contaminated with ethylene glycol. She presents with altered sensorium, severe metabolic acidosis (pH 7.15, HCO₃⁻ 8 mEq/L, anion gap 22), and acute kidney injury (creatinine 2.8 mg/dL). Serum ethylene glycol level is 78 mg/dL. She is intubated for airway protection. What is the most appropriate immediate next step in management?

Explanation

## Clinical Context This is a severe case of ethylene glycol poisoning with: - High serum level (78 mg/dL) — toxic range - Severe metabolic acidosis (pH 7.15) — indicates significant toxic metabolite accumulation - Acute kidney injury — risk of oxalate crystal nephropathy - Altered mental status — CNS toxicity This constellation demands urgent dual therapy: immediate ADH inhibition + haemodialysis. ## Pathophysiology of Ethylene Glycol Toxicity ```mermaid flowchart TD A[Ethylene glycol ingestion]:::outcome --> B[Hepatic alcohol dehydrogenase]:::action B --> C[Glycolaldehyde]:::outcome C --> D[Glycolic acid]:::outcome D --> E[Glyoxylic acid]:::outcome E --> F[Oxalic acid]:::outcome F --> G{Calcium oxalate crystals}:::decision G -->|Kidney| H[Acute tubular necrosis + AKI]:::urgent G -->|CNS| I[Cerebral oedema]:::urgent G -->|Systemic| J[Severe metabolic acidosis]:::urgent H --> K[Permanent renal failure if untreated]:::urgent ``` ## Management Strategy for Severe Ethylene Glycol Poisoning | Intervention | Timing | Rationale | |--------------|--------|----------| | **Fomepizole loading** | **Immediate** | Blocks ADH; stops toxic metabolite formation within minutes | | **Haemodialysis** | **Urgent (concurrent)** | Removes ethylene glycol AND toxic metabolites (glycolic, glyoxylic, oxalic acid); corrects severe acidosis | | **Sodium bicarbonate** | After dialysis initiation | Alkalinizes urine to prevent oxalate precipitation in tubules | | **Thiamine + pyridoxine** | Concurrent | Cofactors for alternative metabolism pathways (minor role) | **Key Point:** In severe ethylene glycol poisoning with high serum level, severe acidosis, or AKI, **both fomepizole AND haemodialysis must be started immediately and concurrently**. Do not delay dialysis waiting for antidote, and do not omit antidote waiting for dialysis. **High-Yield:** Fomepizole dosing in severe cases: - Loading: 15 mg/kg IV over 30 minutes - Maintenance: 10 mg/kg IV every 12 hours for 48 hours - If dialysis is performed: increase frequency to every 4 hours during dialysis (fomepizole is dialysable) **Clinical Pearl:** Ethylene glycol poisoning classically presents in **three phases**: 1. **Phase 1 (0–12 hrs):** CNS depression, intoxication (mimics ethanol) 2. **Phase 2 (12–24 hrs):** Cardiopulmonary manifestations (tachycardia, pulmonary oedema, myocarditis) 3. **Phase 3 (24–72 hrs):** Renal failure, severe acidosis, crystalluria (calcium oxalate monohydrate "needle" crystals) This patient is in Phase 2–3, requiring aggressive intervention. **Warning:** Delaying haemodialysis in the hope that fomepizole alone will suffice is dangerous. Fomepizole prevents *new* toxic metabolite formation but does not remove already-formed formic acid, glycolic acid, or oxalic acid. In severe poisoning with high serum level and AKI, dialysis is mandatory. ## Why Fomepizole + Dialysis (Not Ethanol + Dialysis) - Fomepizole has superior pharmacokinetics and does not cause intoxication - Ethanol is acceptable only if fomepizole is unavailable - In this severe case with AKI, fomepizole is preferred ## Supportive Measures - Correct severe acidosis with sodium bicarbonate (target pH > 7.25) to reduce oxalate precipitation - Thiamine 100 mg IV + pyridoxine 50 mg IV (cofactors for alternative metabolism) - Aggressive fluid resuscitation (avoid hypovolaemia, which worsens AKI) - Monitor serum ethylene glycol, calcium, and renal function hourly [cite:Forensic Medicine & Toxicology (Reddy) Ch 13; Harrison 21e Ch 473; Poisoning & Drug Overdose (Olson) Ch 8]