Makindo Medical Notes

🧪 Alcohol dehydrogenase inhibition is the cornerstone of methanol toxicity treatment. Antidotal therapy — with fomepizole or, if unavailable, ethanol — must be initiated immediately to prevent conversion of methanol into its toxic metabolites, formaldehyde and formic acid. Delay in antidote administration is the single biggest predictor of blindness and death.

📖 About

• Methanol poisoning is a classic example of a treatable toxic metabolic acidosis — it presents with a high anion and osmolar gap and characteristic visual and CNS toxicity.
• Outbreaks occur after ingestion of illicit alcohol (“moonshine”) or adulterated spirits, or through exposure to industrial solvents (e.g., antifreeze, cleaning fluid).
• Even a few millilitres can be lethal: as little as 10 mL may cause blindness; 30 mL can be fatal.

🧬 Aetiology & Pathophysiology

• Methanol itself is relatively inert until metabolised by hepatic enzymes.
• Step 1: Methanol → (via Alcohol Dehydrogenase, ADH) → Formaldehyde.
• Step 2: Formaldehyde → (via Aldehyde Dehydrogenase) → Formic Acid.
• Formic acid is a mitochondrial toxin that inhibits cytochrome oxidase → impaired oxidative phosphorylation → severe lactic acidosis.
• It accumulates particularly in optic nerves and basal ganglia → visual loss and neurological injury.
• Half-life of formic acid ≈ 20 hours (longer in metabolic acidosis or renal failure).

🔍 Common Sources

• Windscreen washer fluid, antifreeze, solvents, model engine fuel.
• Illicit spirits or industrial alcohol substitutes.
• Laboratory methanol or contaminated ethanol-based products.

🧠 Clinical Presentation

• 🕐 Latent phase (6–24h): patient may appear intoxicated or mildly unwell.
• 🧍 Systemic: Headache, dizziness, nausea, vomiting, abdominal pain.
• 🫁 Respiratory: Deep, rapid “Kussmaul” breathing due to metabolic acidosis.
• 👁️ Ophthalmic: Blurred vision, photophobia, “snow field” vision, progressing to blindness (optic neuritis).
• 🧠 Neurological: Confusion, agitation, seizures, coma.
• 🧪 Late: Severe acidosis, renal failure, visual loss, or respiratory arrest.

🧾 Investigations

• Blood tests: FBC, U&E (look for AKI), LFT, calcium (↓), CK if rhabdomyolysis suspected.
• ABG: Metabolic acidosis with raised anion gap (≥16 mmol/L).
• Osmolar gap: Elevated (>10–15 mOsm/kg) — early diagnostic clue before acidosis develops.
• Lactate: Falsely elevated due to formate interference in analyzers.
• Methanol level: Confirmatory but rarely available quickly — do not delay antidote.
• Urinalysis: May show calcium oxalate crystals (if mixed ethylene glycol ingestion).
• Imaging: CT/MRI: bilateral basal ganglia necrosis (putaminal lesions) in delayed cases.

📉 Key Diagnostic Triad

• 1️⃣ High anion gap metabolic acidosis
• 2️⃣ Raised osmolar gap
• 3️⃣ Visual or neurological symptoms

⚕️ Management Overview

Immediate priorities: Resuscitate → Antidote → Correct acidosis → Dialyse → Supplement folate

🏥 1. Immediate Stabilisation

• Secure airway, breathing, and circulation (ABCs).
• Administer oxygen (target SpO₂ 94–98%).
• IV fluids to maintain perfusion and enhance renal clearance.
• Monitor glucose — hypoglycaemia is common.
• Insert urinary catheter if oliguric; assess fluid output.

🧪 2. Antidotal Therapy

• Goal: Inhibit alcohol dehydrogenase to stop toxic metabolite formation.
• Fomepizole (preferred):
  • Loading: 15 mg/kg IV over 30 min.
  • Maintenance: 10 mg/kg every 12 h × 4 doses, then 15 mg/kg every 12 h until methanol <20 mg/dL, pH normalised, and asymptomatic.
  • During haemodialysis: give same dose every 4 h (it is dialysable).
• Ethanol (if fomepizole unavailable):
  • 5% solution: 15 mL/kg loading, then 2 mL/kg/h maintenance.
  • 10% solution: 7.5 mL/kg loading, then 1 mL/kg/h maintenance.
  • 40% spirits (emergency oral): 2 mL/kg loading, then 0.25 mL/kg/h.
  • Double infusion rate for chronic alcohol users (enzyme induction).
• Therapeutic blood ethanol level: 100 mg/dL (22 mmol/L).

🧫 3. Correct Metabolic Acidosis

• Administer IV sodium bicarbonate if pH <7.25 or HCO₃⁻ <15 mmol/L.
• Monitor venous pH, K⁺, and lactate.
• Target pH >7.3 to improve formate metabolism.

🧬 4. Enhance Elimination

• Haemodialysis: Rapidly removes methanol, formate, and corrects acidosis.
• Indications:
  • pH <7.25 or HCO₃⁻ <10
  • Visual symptoms or coma
  • Serum methanol >50 mg/dL (15 mmol/L)
  • Renal failure or rising creatinine
• Continue until methanol undetectable and acidosis resolves.

🌿 5. Cofactor Therapy

• Folinic acid (Leucovorin): 50 mg IV/PO every 4–6 h for 24–48 h. → Accelerates formate metabolism to CO₂ and water.
• If folinic acid unavailable: give Folic acid 50 mg IV or 10 × 5 mg tablets orally.
• Thiamine (100 mg IV) and pyridoxine (50 mg IV) are added if ethylene glycol ingestion possible.

⚠️ 6. Monitoring

• Repeat ABG, osmolar gap, and electrolytes every 2–4 hours.
• Monitor vision daily — irreversible damage may occur within 24 h.
• Maintain careful fluid balance; watch for pulmonary oedema if large fluid loads given.

🧩 Treatment Summary Table

🚫 Contraindications

• No absolute contraindication to antidote therapy — delay is more harmful.
• Relative: known allergy to fomepizole (use ethanol instead).

💊 Common Side Effects of Antidotes

• Ethanol: Hypoglycaemia, CNS depression, hypotension.
• Fomepizole: Headache, mild rash, transient ↑ liver enzymes, injection-site irritation.

📚 References

• Methanol Intoxication: Diagnostic and Treatment Approach. Am J Kidney Dis 2016.
• Methanol Poisoning Information (Methanol Institute)
• TOXBASE: Methanol and Ethylene Glycol Management Guidelines
• Brent J. “Fomepizole for Toxic Alcohol Poisoning.” N Engl J Med 2009;360:2216–2223.