What are the clinical features, differential diagnosis, and management of methanol poisoning?

Methanol Poisoning: Clinical Features, Differential Diagnosis, and Management

Clinical Features

Methanol poisoning presents in a characteristic biphasic pattern with an initial phase of mild intoxication followed by a latent period of 12-24 hours before severe metabolic acidosis and visual disturbances develop. 1, 2

Initial Presentation (0.5-4 hours post-ingestion)

• Gastrointestinal symptoms: Nausea, vomiting, and abdominal pain 1, 2
• CNS depression: Mild central nervous system suppression similar to ethanol intoxication 1, 2
• Inebriation without the smell of alcohol on breath (important clinical clue) 3

Late Presentation (12-24 hours post-ingestion)

• Visual disturbances: Blurred vision progressing to complete blindness—this is the pathognomonic feature 1, 2
• Blurred vision with normal consciousness is a strong suspicious sign of methanol poisoning 1
• Severe metabolic acidosis: Uncompensated high anion gap metabolic acidosis 1, 2
• Respiratory distress: Breathlessness due to metabolic acidosis 3
• Progressive CNS depression: Can progress to coma 3

Key Prognostic Indicators

• Severity of CNS depression, hyperglycemia, and metabolic acidosis correlate with mortality—NOT the serum methanol concentration itself 1
• The interval between ingestion and treatment initiation is more predictive of outcome than initial methanol level 4

Differential Diagnosis

Methanol toxicity must be distinguished from other causes of high anion gap metabolic acidosis using the mnemonic approach. 5

High Anion Gap Metabolic Acidosis Differential

• Ethylene glycol poisoning: Look for calcium oxalate crystals in urine, renal failure 5
• Lactic acidosis: Measure blood lactate 5
• Diabetic ketoacidosis: Check glucose, ketones 5
• Salicylate toxicity: Measure serum salicylate level 5
• Chronic renal failure: Assess renal function 5

Diagnostic Laboratory Criteria

• Anion gap calculation: Na⁺ - (Cl⁻ + HCO₃⁻); an anion gap >27 mmol/L indicates severe toxicity requiring hemodialysis even with fomepizole** 5
• Osmolar gap: Elevated >10-50 mOsm/kg (depending on clinical context) 5
• Osmolar gap formula: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 5

Important Caveats

• Both osmolar gap and anion gap can be normal or minimally elevated depending on timing of presentation and coingestion of ethanol 6
• If ethanol was coingested, methanol metabolism is delayed, potentially masking the osmolar gap 6
• As methanol is metabolized to formate, the osmolar gap decreases while the anion gap increases 6

Management

Begin fomepizole treatment immediately upon suspicion of methanol poisoning based on history, anion gap metabolic acidosis, increased osmolar gap, visual disturbances, OR documented methanol concentration >20 mg/dL. 7

Immediate Resuscitation and Antidote Administration

First-Line Antidote: Fomepizole

Fomepizole is the preferred first-line antidote due to its superior safety profile, simpler dosing, and more predictable pharmacokinetics compared to ethanol. 8, 2

Dosing Protocol 7:

• Loading dose: 15 mg/kg IV over 30 minutes
• Maintenance: 10 mg/kg IV every 12 hours for 4 doses
• Then: 15 mg/kg IV every 12 hours thereafter until methanol <20 mg/dL and patient is asymptomatic with normal pH 7

During hemodialysis: Increase frequency to every 4 hours due to dialyzability 7

Alternative Antidote: Ethanol

• Use ethanol ONLY when fomepizole is unavailable 8, 2
• Ethanol has significant disadvantages: Complex dosing, need for blood level monitoring, risk of hypoglycemia, CNS depression, and higher medication error rates 8, 2

Correction of Metabolic Acidosis

• Administer intravenous sodium bicarbonate to correct acidosis 4, 2
• Acidosis correction is critical as it reduces formic acid diffusion into cells and decreases ocular toxicity 2

Folinic Acid Administration

• Administer intravenous folinic acid to enhance formic acid metabolism to carbon dioxide and water 2
• This enhances the activity of 10-formyl tetrahydrofolate synthetase, the enzyme that converts formate to CO₂ and H₂O 2

Hemodialysis Indications

Hemodialysis should be initiated in addition to fomepizole for: 7

• Methanol concentration ≥50 mg/dL 7
• Severe metabolic acidosis (anion gap >27 mmol/L) despite fomepizole treatment 8
• Renal failure 7
• Significant or worsening metabolic acidosis 7
• Visual disturbances 4

Hemodialysis modality preference 9:

• Intermittent hemodialysis is preferred over continuous renal replacement therapy when available 9
• CRRT is acceptable if intermittent hemodialysis cannot be initiated quickly 9

Cessation Criteria

Discontinue treatment when: 7

• Methanol concentration is undetectable or <20 mg/dL 7
• Patient is asymptomatic with normal pH 7
• Anion gap <18 mmol/L 9

Special Considerations

Coingestions

• If intentional poisoning is suspected, obtain toxicology screening for coingestions, particularly ethanol 9
• 66% of intentional poisonings involve ethanol coingestion 9
• Ethanol coingestion delays methanol metabolism and can mask early toxicity 3

Follow-up

• All patients require clinical follow-up 1-2 months after treatment 9
• Late cognitive impairments can develop including memory disturbance, depression, anxiety, and vestibular problems 9
• Patients not recovered to baseline should undergo formal neuropsychological evaluation 9
• Mandatory psychiatric evaluation for all intentional poisonings due to high suicide completion risk 9

Critical Pitfalls to Avoid

• Do NOT delay treatment waiting for methanol levels—treat based on clinical suspicion 7, 1
• Do NOT rely solely on methanol concentration to predict severity—acidosis and CNS depression are better prognostic indicators 1
• Do NOT withhold fomepizole if hemodialysis is unavailable—fomepizole alone can prevent toxicity if given early 8
• Do NOT use polycarbonate syringes or needles when administering fomepizole as it can compromise syringe integrity 7
• Do NOT assume normal osmolar or anion gaps exclude methanol poisoning—timing and coingestions affect these values 6