A 28-year-old woman is admitted to a tertiary care hospital in Mumbai with a 2-hour history of nausea, vomiting, abdominal pain, and altered consciousness. She had ingested an unknown quantity of antifreeze fluid 4 hours prior. Laboratory investigations reveal: pH 7.22, HCO₃⁻ 10 mEq/L, anion gap 18, serum calcium 6.2 mg/dL (low), and urine microscopy shows needle-shaped crystals. Serum osmolality is 310 mOsm/kg. What is the most appropriate immediate intervention?

Explanation

## Clinical Diagnosis: Ethylene Glycol Poisoning ### Pathognomonic Features of Ethylene Glycol Toxicity **Key Point:** Ethylene glycol (found in antifreeze) is metabolized to **glycolic acid and oxalic acid**, causing: 1. **High-anion-gap metabolic acidosis** (pH 7.22, HCO₃⁻ 10, anion gap 18) 2. **Hypocalcaemia** (serum Ca 6.2 mg/dL) due to precipitation of calcium oxalate 3. **Needle-shaped calcium oxalate crystals in urine** (pathognomonic) 4. **Elevated serum osmolality** (310 mOsm/kg) ### Metabolic Pathway of Ethylene Glycol $$\text{Ethylene glycol} \xrightarrow{\text{ADH}} \text{Glycolaldehyde} \xrightarrow{\text{LDH}} \text{Glycolic acid} \xrightarrow{} \text{Oxalic acid}$$ Oxalic acid binds calcium → **calcium oxalate precipitation** → hypocalcaemia and crystalluria. ### Comparison: Ethylene Glycol vs. Methanol | Feature | Ethylene Glycol | Methanol | |---------|-----------------|----------| | **Source** | Antifreeze, coolant | Industrial solvent, illicit alcohol | | **Latent period** | 1–12 hours | 6–24 hours | | **Visual symptoms** | Absent | Prominent (photophobia, blindness) | | **Optic nerve involvement** | No | Yes (optic disc hyperaemia) | | **Serum calcium** | Low (hypocalcaemia) | Normal | | **Urine crystals** | Calcium oxalate (needle-shaped) | Absent | | **Renal involvement** | Severe (acute kidney injury) | Mild | | **Cardiac involvement** | Myocarditis, pulmonary oedema | Rare | | **Metabolite** | Glycolic acid, oxalic acid | Formic acid | **High-Yield:** The **triad of metabolic acidosis + hypocalcaemia + calcium oxalate crystals** is diagnostic of **ethylene glycol poisoning**. ### Immediate Management Protocol ```mermaid flowchart TD A[Ethylene glycol poisoning suspected]:::outcome --> B{Fomepizole available?}:::decision B -->|Yes| C[Fomepizole 15 mg/kg IV loading]:::action B -->|No| D[Ethanol 10% IV: loading 7-10 mL/kg]:::action C --> E[Sodium bicarbonate to correct acidosis]:::action D --> E E --> F[Calcium gluconate for hypocalcaemia]:::action F --> G{Severe renal failure or high glycol level?}:::decision G -->|Yes| H[Hemodialysis + continuous ADH inhibition]:::action G -->|No| I[Continue ADH inhibitor + supportive care]:::action H --> J[Monitor urine output, renal function, electrolytes]:::outcome I --> J ``` ### Specific Treatment Steps 1. **ADH Inhibition (First-line):** - **Fomepizole:** 15 mg/kg IV loading, then 10 mg/kg every 12 hours (preferred) - **Ethanol:** If fomepizole unavailable (10% IV solution, target blood ethanol 100–150 mg/dL) 2. **Correct Metabolic Acidosis:** - **Sodium bicarbonate:** 1–2 mEq/kg IV to target pH > 7.30 - Alkalinization enhances renal excretion of glycolic acid 3. **Treat Hypocalcaemia:** - **Calcium gluconate:** 10–20 mL of 10% solution IV (monitor for arrhythmias) - Correct only if symptomatic (tetany, seizures, QT prolongation) 4. **Hemodialysis Indications:** - Severe metabolic acidosis (pH < 7.25) - Acute kidney injury - Serum ethylene glycol > 50 mg/dL - Refractory hypocalcaemia - Pulmonary oedema or myocarditis **Clinical Pearl:** Fomepizole is superior to ethanol because it does not cause CNS depression, hypoglycaemia, or lactic acidosis, and has predictable kinetics. ### Why Calcium Oxalate Crystals Are Diagnostic Calcium oxalate precipitates in: - **Urine** → needle-shaped monohydrate crystals (pathognomonic) - **Serum** → hypocalcaemia, tetany, arrhythmias - **Tissues** → acute kidney injury, myocarditis **Warning:** Hypocalcaemia can cause life-threatening arrhythmias (prolonged QT, Torsades de Pointes). Monitor ECG continuously.