A 32-year-old man is brought to the emergency department 6 hours after ingesting approximately 100 mL of methanol-contaminated alcohol at a local distillery. He is conscious, alert, and complains of visual disturbances (blurred vision) and mild abdominal pain. Vital signs are stable. Serum methanol level is 45 mg/dL. Arterial blood gas shows pH 7.28, HCO₃⁻ 16 mEq/L, and normal anion gap at present. What is the most appropriate immediate next step in management?

Explanation

## Clinical Context Methanol poisoning presents with a triad of visual disturbances, metabolic acidosis, and CNS depression. The patient has confirmed methanol ingestion with detectable serum level and early signs of toxicity (visual disturbance, mild acidosis). Early intervention before severe metabolic acidosis develops is critical. ## Mechanism of Methanol Toxicity Methanol itself is relatively non-toxic; however, hepatic alcohol dehydrogenase (ADH) metabolizes it to formaldehyde and then formic acid, which causes: - Severe metabolic acidosis (anion gap) - Optic nerve and retinal damage (permanent blindness if untreated) - CNS depression ## Management Algorithm ```mermaid flowchart TD A[Methanol ingestion confirmed]:::outcome --> B{Serum methanol level & clinical signs?}:::decision B -->|Level > 20 mg/dL OR symptomatic| C[Inhibit ADH metabolism]:::action C --> D{Fomepizole available?}:::decision D -->|Yes| E[Fomepizole 15 mg/kg IV loading]:::action D -->|No| F[Ethanol 10% IV to achieve 100-150 mg/dL]:::action E --> G[Maintenance: 10 mg/kg Q12H for 48 hrs]:::action F --> G G --> H[Haemodialysis if severe acidosis or level > 50 mg/dL]:::action H --> I[Continue antidote until methanol undetectable]:::outcome ``` ## Why Fomepizole Over Ethanol | Feature | Fomepizole | Ethanol | |---------|-----------|----------| | **Mechanism** | Competitive ADH inhibitor (Ki ~0.02 μM) | Competitive ADH inhibitor (Ki ~1 mM) | | **Selectivity** | Highly selective for ADH | Non-selective; CNS effects | | **Monitoring** | No blood level monitoring needed | Requires frequent blood ethanol levels | | **Hypoglycaemia risk** | None | Yes (especially in fasting patients) | | **Adverse effects** | Minimal; rare headache, rash | Intoxication, hypoglycaemia, seizures | | **Preferred agent** | **First-line in most centres** | Backup if fomepizole unavailable | **Key Point:** Fomepizole is the antidote of choice for methanol poisoning in modern practice. It has superior pharmacokinetics, does not cause intoxication, and does not require frequent blood level monitoring. **High-Yield:** The goal of ADH inhibition is to prevent formation of formic acid while the body eliminates unchanged methanol via respiration and renal excretion. Fomepizole dosing: loading 15 mg/kg IV, then 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every 12 hours if methanol still detectable. **Clinical Pearl:** Visual disturbances (blurred vision, photophobia, "snow-field" vision) are pathognomonic for methanol toxicity and indicate optic nerve involvement. Early fomepizole administration can prevent permanent blindness. **Warning:** Do not delay antidote therapy while waiting for confirmatory tests. If methanol poisoning is suspected clinically (history + visual symptoms + metabolic acidosis), initiate fomepizole immediately. ## Indications for Haemodialysis - Serum methanol > 50 mg/dL - Severe metabolic acidosis (pH < 7.25) - Renal failure - Neurological or cardiac complications This patient has mild acidosis and moderate methanol level, so fomepizole monotherapy is appropriate now; haemodialysis may be needed if acidosis worsens. [cite:Forensic Medicine & Toxicology (Reddy) Ch 13; Harrison 21e Ch 473]