What are the diagnostic criteria and treatment for methanol toxicity?

Diagnosis of Methanol Toxicity

Methanol toxicity should be diagnosed based on clinical suspicion combined with metabolic acidosis (high anion gap), elevated osmolar gap, and confirmed by serum methanol concentration >20 mg/dL or elevated serum formate levels, with treatment initiated immediately upon suspicion without waiting for confirmatory testing. 1

Clinical Presentation

The diagnosis requires high clinical suspicion as methanol poisoning can be elusive 2. Key clinical features include:

• Initial symptoms: Nausea, vomiting, abdominal pain, and mild CNS depression 3
• Latent period: 12-24 hours following ingestion before severe toxicity develops 3
• Late manifestations: Visual disturbances (blurred vision, altered visual fields, complete blindness), severe metabolic acidosis, seizures, stupor, and coma 1, 3
• Neurologic findings: Ataxia may occur with methanol toxicity 4

Laboratory Diagnostic Criteria

Primary Diagnostic Tests

Metabolic acidosis with elevated anion gap is the hallmark finding 1, 2:

• Calculate anion gap as: Na⁺ - (Cl⁻ + HCO₃⁻) 4
• Anion gap >27 mmol/L indicates severe toxicity requiring hemodialysis even with fomepizole 5

Elevated osmolar gap (>10-50 mOsm/kg depending on clinical context) 4:

• Calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 4
• Osmolar gap may be absent if presentation is delayed and methanol has already been metabolized 6

Serum methanol concentration >20 mg/dL confirms poisoning and mandates treatment 1:

• Methanol >50 mg/dL (>50 mmol/L) indicates need for hemodialysis 5, 1
• Gas or liquid chromatography is definitive but often unavailable acutely 6

Emerging Diagnostic Test

Serum formate measurement is highly sensitive and specific 7:

• Normal upper limit: 2 mg/dL (0.4 mmol/L) 7
• Elevated formate detected in 14 of 15 methanol-poisoned patients, including asymptomatic cases 7
• More sensitive than anion gap or osmolar gap at low methanol concentrations 7
• Bedside formate test strips are under development and have shown promise in clinical cases 8

Diagnostic Algorithm

Initiate treatment immediately upon suspicion based on ANY of the following 1:

1. Patient history of methanol ingestion (windshield washer fluid, antifreeze, model airplane fuel, illicit alcohol) 6
2. Anion gap metabolic acidosis (unexplained high anion gap) 1
3. Increased osmolar gap 1
4. Visual disturbances (blurred vision, blindness) 1
5. Oxalate crystals in urine (though this suggests ethylene glycol rather than methanol) 1
6. Documented methanol concentration >20 mg/dL 1

Important Caveats

• Do not wait for confirmatory methanol levels to begin treatment—the diagnosis may be difficult because methanol concentrations diminish as they are metabolized 1
• Absence of acidosis does not rule out poisoning: Early presentation or concomitant ethanol ingestion can mask acidosis 7, 6
• Both anion gap and osmolar gap can be normal depending on timing of presentation 6
• Repeated testing may be necessary in patients developing metabolic acidosis after initial normal results 7

Differential Diagnosis

Methanol toxicity must be distinguished from other causes of high anion gap metabolic acidosis 4:

• Lactic acidosis
• Diabetic ketoacidosis
• Ethylene glycol poisoning (look for calcium oxalate crystals in urine) 4
• Salicylate toxicity
• Chronic renal failure 4

Measure blood lactate, serum salicylate, and consider ethylene glycol levels when the diagnosis is uncertain 4.

Monitoring Parameters

Once diagnosed, frequently monitor 1:

• Arterial blood gases for pH and acid-base status
• Serum electrolytes for anion gap calculation
• Methanol concentrations to guide treatment duration
• Formate levels if available 7