Makindo Medical Notes

Related Subjects: |Drug Toxicity - clinical assessment |Metabolic acidosis |Aspirin or Salicylates toxicity |Ethylene glycol toxicity |Ethanol toxicity |Methanol toxicity |Ricin toxicity |Carbon Tetrachloride Toxicity |Renal Tubular Acidosis |Lactic acidosis |Iron Toxicity |Tricyclic Antidepressant Toxicity |Opiate Toxicity |Carbon monoxide Toxicity |Benzodiazepine Toxicity |Paracetamol (Acetaminophen) toxicity |Amphetamine toxicity |Beta Blocker toxicity |Calcium channel blockers toxicity |Cannabis toxicity |Cyanide toxicity |Digoxin Toxicity |Lithium Toxicity |NSAIDS Toxicity |Ecstasy toxicity |Paraquat toxicity |Quinine toxicity |SSRI Toxicity |Theophylline Toxicity |Organophosphate (OP) Toxicity |Toxin elimination by dialysis |Drug Toxicity with Specific Antidotes

Alcohol dehydrogenase inhibition is crucial and must be administered as quickly as possible. This can be achieved by administering ethanol or fomepizole to prevent the metabolism of methanol into its toxic metabolites, formic acid and formaldehyde.

About

• Methanol poisoning is particularly concerning as it is treatable and presents with characteristic blood chemistry abnormalities.
• Methanol has been illicitly added to alcoholic beverages, increasing the risk of accidental ingestion.
• Even a small quantity, such as a single mouthful, can cause irreversible toxicity.

Aetiology

• Methanol is relatively harmless until it is metabolized by the body.
• Methanol is metabolized by Alcohol Dehydrogenase (ADH) into formaldehyde.
• Formaldehyde is further metabolized by Formaldehyde Dehydrogenase into formic acid.
• The metabolites, particularly formic acid, cause renal failure and a raised anion gap metabolic acidosis.
• Formic acid metabolizes slowly in the human body, with a half-life of about 20 hours.

Sources

• Windscreen washer fluid and other cleaning solvents.
• Antifreeze solutions and illicitly produced alcoholic beverages ("Moonshine").

Clinical Presentation

• Neurological symptoms such as dilated or fixed pupils, coma, convulsions, and blindness.
• Systemic symptoms including lethargy, Kussmaul respiration (deep, rapid breathing), and renal failure (acute tubular necrosis).
• Gastrointestinal symptoms like abdominal pain, nausea, vomiting, and in late stages, respiratory arrest.
• Ophthalmic manifestations include crystal formation within the eye, leading to 'snow field' cataract formation.

Investigations

• Laboratory Tests:
  • Full Blood Count (FBC), Urea & Electrolytes (U&E) may indicate acute kidney injury (AKI).
  • Lactate levels are typically elevated.
  • Arterial Blood Gas (ABG) shows metabolic acidosis with an increased anion gap and serum osmolar gap.
  • Hypoglycemia and hypocalcemia should be monitored and treated as necessary.
  • Methanol levels can be definitively diagnosed with gas or liquid chromatography, though these methods are laborious and expensive.
  • Creatine Kinase (CK) levels if there is concern for rhabdomyolysis.
• Imaging:
  • Electrocardiogram (ECG) to monitor cardiac function.

Management

• Criteria for Treatment:
  • Criterion A: Asymptomatic patients with normal blood gas - Observe.
  • Criterion B: pH >7.2 and HCO₃⁻ >20 - Observe for a minimum of 24 hours and administer bicarbonate if necessary due to increasing acidosis.
  • Criterion C: pH between 7.0-7.2 and HCO₃⁻ between 10-20 - Administer bicarbonate and ethanol (or fomepizole), and consider hemodialysis.
  • Criterion D: pH <7.2 and HCO₃⁻ <10 - Administer bicarbonate, fomepizole (or ethanol), hemodialysis, and folinic acid.
• Alcohol (Ethanol) Administration:
  • 5% Ethanol: Start with a loading dose of 15 mL/kg, followed by 2 mL/kg/hr.
  • 10% Ethanol: Start with a loading dose of 7.5 mL/kg, followed by 1 mL/kg/hr.
  • 20% Ethanol: Start with a loading dose of 4 mL/kg, followed by 0.5 mL/kg/hr.
  • 40% Ethanol: Start with a loading dose of 2 mL/kg, followed by 0.25 mL/kg/hr.
  • Double the infusion rate if the patient is a regular drinker.
• Fomepizole Administration:
  • Loading dose of 15 mg/kg, followed by 10 mg/kg every 12 hours.
  • If available quickly, administer fomepizole upon suspicion of methanol ingestion, anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or serum methanol concentration >20 mg/dL.
• Prompt Poison Control Consultation:
  • Obtain immediate advice from the National Poisons Information Service for the management of ethylene glycol and methanol poisoning.
  • Ensure the ABC (Airway, Breathing, Circulation), close monitoring, and administer oxygen to maintain oxygen saturation between 94-98%.
  • Provide intravenous fluids to maintain good diuresis.
  • Consider intravenous bicarbonate to correct severe acidosis (pH level <7.2).
  • Administer an alcohol loading dose of 50 g of ethanol (approximately 125 ml of gin, whisky, or vodka) orally immediately. Ethanol competes with methanol for alcohol dehydrogenase, reducing methanol metabolism.
  • Initiate intravenous ethanol infusion:
    • 10 mL/kg of ethanol in 5% Dextrose to achieve blood ethanol concentrations of 500 mg/L to 1 g/L.
    • Continue infusion until methanol is no longer detectable in the blood.
    • Closely monitor pH, anion gap, ABG, and renal function.
  • Administer fomepizole:
    • Loading dose of 15 mg/kg, followed by 10 mg/kg every 12 hours.
    • If available quickly, administer fomepizole upon suspicion of methanol ingestion, anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or serum methanol concentration >20 mg/dL.
  • Consider folinic acid (or folic acid):
    • 50 mg IV or orally (e.g., 10 tablets of 5 mg) every 6 hours for 24-48 hours.
  • Consider hemodialysis:
    • Indicated for pH <7.25, HCO₃⁻ <10, acute renal failure, visual disturbances >50%, or serum glycolic acid >8 mg/dL.
    • Contact the local renal unit early and proceed with dialysis until methanol is no longer detectable.

References

• Methanol Intoxication Approach
• Methanol Poisoning Information