A 35-year-old woman is brought to the emergency department 3 hours after ingesting an unknown substance. She presents with altered sensorium, hypocalcemia (7.2 mg/dL), hyperammonemia, and acute kidney injury (creatinine 2.8 mg/dL). Arterial blood gas shows metabolic acidosis (pH 7.22, HCO₃⁻ 12 mEq/L) with an anion gap of 18. Urine microscopy reveals needle-shaped calcium oxalate monohydrate crystals. Serum osmolality is 340 mOsm/kg with an osmolar gap of 28. What is the most appropriate immediate intervention?

Explanation

## Clinical Diagnosis: Ethylene Glycol Poisoning with Acute Kidney Injury ### Recognition of Ethylene Glycol Toxicity **Key Point:** Ethylene glycol poisoning is characterized by the triad of **metabolic acidosis, hypocalcemia, and acute kidney injury** — the presence of **calcium oxalate monohydrate crystals in urine is pathognomonic**. ### Diagnostic Features in This Case | Feature | Finding | Significance | |---------|---------|-------------| | **Onset** | 3 hours | Early (2–6 hour window) | | **Metabolic acidosis** | pH 7.22, HCO₃⁻ 12, AG 18 | Glycolic acid accumulation | | **Hypocalcemia** | 7.2 mg/dL | Calcium oxalate precipitation in tissues | | **Acute kidney injury** | Cr 2.8 mg/dL | Crystal-induced acute tubular necrosis | | **Urine crystals** | Calcium oxalate monohydrate (needle-shaped) | **Pathognomonic for ethylene glycol** | | **Osmolar gap** | 28 mOsm/kg | Unmeasured osmoles (parent ethylene glycol) | | **Hyperammonemia** | Present | Metabolic derangement from glycolic acid | **High-Yield:** The **calcium oxalate monohydrate crystals** are the diagnostic hallmark of ethylene glycol poisoning and differentiate it from methanol (no crystals) and isopropanol (no crystals or acidosis). ### Pathophysiology of Ethylene Glycol Toxicity ```mermaid flowchart TD A[Ethylene glycol ingestion]:::outcome --> B[Rapid GI absorption]:::action B --> C[Alcohol dehydrogenase metabolism]:::action C --> D[Glycolaldehyde formation]:::outcome D --> E[Glycolic acid accumulation]:::urgent E --> F[Metabolic acidosis + hypocalcemia]:::urgent E --> G[Oxalic acid formation]:::outcome G --> H[Calcium oxalate crystals in kidneys]:::urgent H --> I[Acute kidney injury]:::urgent E --> J[CNS depression, altered mental status]:::urgent ``` ### Why Fomepizole + Hemodialysis + Calcium Supplementation Is Correct **1. Fomepizole (4-methylpyrazole):** - **Mechanism:** Competitive inhibitor of alcohol dehydrogenase (ADH); prevents conversion of ethylene glycol to toxic metabolites (glycolaldehyde → glycolic acid → oxalic acid) - **Dosing:** 15 mg/kg IV bolus, then 10 mg/kg every 12 hours until serum ethylene glycol is undetectable or < 20 mg/dL - **Timing:** Must be given urgently; efficacy decreases as toxic metabolites accumulate - **Advantage over ethanol:** Fomepizole has higher affinity for ADH (Km 1.9 mM vs. ethanol's Km 1 mM) and does not cause CNS depression **2. Hemodialysis:** - **Indications in this patient:** - Acute kidney injury (Cr 2.8 mg/dL) - Severe metabolic acidosis (pH 7.22) - Hypocalcemia (7.2 mg/dL) - Clinical toxicity (altered mental status) - **Dual benefit:** Removes both parent ethylene glycol AND toxic metabolites (glycolic acid, oxalic acid) - **Timing:** Should be initiated immediately; delays worsen outcomes **3. Calcium Supplementation:** - **Indication:** Symptomatic hypocalcemia (7.2 mg/dL; normal 8.5–10.5 mg/dL) - **Mechanism:** Calcium oxalate precipitates in tissues, depleting serum calcium; supplementation restores ionized calcium - **Dosing:** 10% calcium gluconate 10–20 mL IV over 2–5 minutes; monitor for QT prolongation - **Monitoring:** Serial serum calcium, phosphate, and magnesium **4. Supportive Care:** - Sodium bicarbonate for alkalinization (enhances renal excretion of glycolic acid) - Thiamine and pyridoxine (cofactors for alternative metabolism pathways) - Correction of electrolyte abnormalities **Mnemonic: FOMEPIZOLE HEMODIALYSIS CALCIUM = FHC** - **F** = Fomepizole (ADH inhibitor) - **H** = Hemodialysis (removes parent + metabolites) - **C** = Calcium supplementation (corrects hypocalcemia) [cite:Harrison 21e Ch 473; Park 26e Ch 24] ### Clinical Pearl **Clinical Pearl:** In ethylene glycol poisoning with acute kidney injury, hemodialysis is **not optional** — it is mandatory. Fomepizole alone cannot prevent kidney damage once glycolic acid has accumulated; dialysis removes both the parent compound and its toxic metabolites while the kidneys recover.