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 needed as quickly as possible by giving alcohol or fomepizole to prevent the metabolism of Methanol to its toxic metabolites formic acid and formaldehyde.

About

• Interesting as they are treatable and cause characteristic blood chemistry
• Methanol has been added to alcoholic drinks.
• Even a mouthful can cause irreversible toxicity

Aetiology

• Methanol is harmless until metabolised
• Methanol ? (Alcohol Dehydrogenase) ? Formaldehyde
• Formaldehyde ? (Formaldehyde dehydrogenase) ? Formic acid
• The metabolites 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.

Source

• Windscreen washer fluid, Cleaning solvents
• Antifreeze, "Moonshine"

Clinical

• Dilated or fixed pupils, Coma and Convulsions, blindness
• Lethargy, Kussmaul respiration, Renal failure (ATN), Parkinsonism
• Abdominal pain, Nausea, Vomiting and late stages can cause respiratory arrest
• Crystals forming within the eye can lead to so-called 'snow field' cataract formation.

Investigations

• FBC, U&E - may show AKI. ECG
• Lactate is typically high
• ABG: Metabolic acidosis + increased anion gap and serum osmolar gap
• Hypoglycaemia: monitor and treat
• Hypocalcaemia
• Methanol: Definitive diagnosis of methanol intoxication presently requires measurement with gas or liquid chromatography, a labourious and expensive procedure.
• CK: if there is concern of rhabdomyolysis

Management: Criteria

• Criterion for treatment (patients' blood gases):
• A. Asymptomatic patients, normal blood gas: Observe.
• B. pH>7.2, HCO₃>20: Observe minimum 24 hours. Give bicarbonate if necessary (increasing acidosis)
• C. pH 7.0-7.2, HCO₃ 10-20: Give bicarbonate, ethanol (or fomepizole), consider HD
• D. pH<7.2, HCO₃<10: Give bicarbonate, fomepizole (or ethanol), HD, folinic acid

Ethanol (double infusion rate if regular drinker)

• 5% Ethanol start at 15 mL/kg and then 2 ml/kg/hr
• 10% Ethanol start at 7.5 mL/kg and then 1 ml/kg/hr
• 20% Ethanol start at 4 mL/kg and then 0.5 ml/kg/hr
• 40% Ethanol start at 2 mL/kg and then 0.25 ml/kg/hr

Management: Take prompt poisons advice

• Advice on the treatment of ethylene glycol and methanol poisoning should be obtained from the National Poisons Information Service
• ABC, close monitoring, Oxygen to give sats of 94-98%. IV fluids to maintain good diuresis. Consider IV bicarbonate to correct severe acidosis (pH level <7.2)
• Alcohol loading dose: of 50 g of ethanol (conveniently given as approximately 125 ml of gin, whisky, or vodka) * should be administered immediately orally. It has an affinity in the order of 100 (some say 8,000) times that of methanol for alcohol and aldehyde dehydrogenases
• IV (Ethyl) Alcohol infusion: intravenous infusion of ethanol usually 10ml/kg in 5% Dextrose to provide blood ethanol concentrations of 500 mg to 1 g/l. The infusion should be continued until ethylene glycol is no longer detectable in the blood. Keep a close watch on pH and Anion gap as well as ABG and renal function.
• Fomepizole loading dose 15 mg/kg then 10 mg/kg every 12 hours. if it can be quickly obtained: give on suspicion of methanol ingestion and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, serum methanol concentration greater than 20 mg/dL
• Consider FOLINIC (OR FOLIC) ACID: 50 mg iv. or orally (e.g. 10 tablets of 5 mg) every 6 hours for 24-48 hrs.
• Consider Bicarbonate IV
• Consider haemodialysis as a treatment method and contact local renal unit early and dialyse until no ethylene glycol is detectable in the blood. Indications include pH < 7.25, HCO₃ < 10, Acute renal failure, Visual disturbance >50, Serum glycolic acid >8

References

• Methanol intoxication approach
• methanol poisoning