Clinical manifestations of methanol poisoning .pptx

A note on the toxicological profile of patients with methanol poisoning

1. Methanol Poisoning Chief : Prof Dr Sathish Kumar M.D., Assistant Professors : Dr. L.Muthumani D.A.,M.D.,FRCP Dr. M. Anbarasan M.D., Unit M3

2. Introduction Grains (barley, wheat,corn) Grapes Fermentation Fermentation Beer Wine Distillation Distillation Whiskey Brandy

3. Indian scenario Molasses (Sugar cane) Fermentation using yeast Alcohol (8-10%) Fractional Distillation (Methanol 65 ℃ Ethanol 78 ℃) Ethanol is separated (99% purity, diluted to 40-42%, flavours and colours are added and marketed as Spirit (whiskey, Brandy, Vodka)

4. Illicit liquor Rudimentary methods of fractional distillation To increase yield, urea is added (as a nourishment for yeast) Zinc acts a catalyst to fermentation process ( Batteries ) Rectified spirit (Industrial alcohol) Toxic alcohol ( Ethanol +methanol + ethylene glycol + aldehyde)

5. Methanol Colourless, volatile and slightly sweet Rapidly absorbed from GIT (Peak level 30-60 min) Transdermal, inhalational LETHAL DOSE 15 mL of 40% methanol 4 mL pure methanol - Blindness Metabolism - Hepatic (90%)

6. Pharmacokinetics Methanol per-se is non toxic Formic acid is toxic Toxicity is potentiated by metabolic acidosis Formic acid is degraded to Carbon dioxide and water

7. Clinical features 12- 24 hours Severe or unusual drowsiness Hyperventilation (Metabolic acidosis) GI symptoms Visual disturbances - Blurring, dense central scotoma Neurological signs Coma and death

8. Differential diagnosis Sepsis Renal failure DKA or MALA Alcoholic ketoacidosis (most difficult) RL + Thiamine + Dextrose challenge improves acidosis Avoid bicarb

9. Poor prognosis Coma on admission severe metabolic acidosis (HCO3 <10mmol/L (<10mEq), BD>15 mmol/L, pH typically <7.0) lack of hyperventilation despite this severe acidosis S-methanol is not prognostic.

10. Management When there is one, there is usually many Public health issue ABC D - Decontamination Sodium bicarbonate Antidotes (Fomipizole / Ethanol) Folic acid RRT Supportive care

11. Sodium bicarbonate Acidosis potentiates Formic acid toxicity by decreasing its renal elimination Initial aggressive management Immediate bicarb if pH < 7.0 Consider bicarb after Fluid+thiamine+dextrose in mod- mild acidosis Dose ( aim a full correction) (0.3 x weight x base deficit (BD)) = mmol buffer (bicarbonate) If base deficit >20 - give a minimum of 500 mmol over 0.5-1 hour If ABG is NA, give 150-250 mmol until hyperventilation settles If IV soda bicarb is not available,10 tablets (500mg strength)

12. Antidotes Fomipizole ( 4- methyl pyrazole) - preferred first line stronger competitive inhibitor of ADH doesnt cause sedation unlike Ethanol 1.5 g/ 1.5 mL > Loading dose 15 mg/kg IV infusion over 30 min, THEN > 10 mg/kg IV every 12hr for 4 doses, THEN > increase to 15 mg/kg every 12hr after 5th dose (inducing its own metabolism) > Dosing during haemodialysis (HD) 10mg/kg Q4H Cost, orphan drug, auto induction

13. Ethanol Ethanol competes with methanol for ADH, thus preventing metabolism of methanol to its toxic by-products ADH has greater affinity for ethanol Dose Aim : ethanol blood concentration of 100 – 150 mg/dl IV or orally or via NG tube with the same rates 10% ethanol solution should be utilized for IV administration Any ethanol solution can be administered orally or through a nasogastric tube, but concentrations of 40% or above should be diluted Monitor ABG, blood glucose

14. Folic Acid To enhance folate-dependent metabolism of formic acid to carbon dioxide and water, thus reducing toxic metabolites of methanol. RENAL REPLACEMENT THERAPY (6-8 hrs) Small molecule, less bound to protein, low Vd ⎯ New visual disturbances (concomitant metabolic acidosis or detected methanol level) ⎯ Severe metabolic acidosis ⎯ > 30mL of methanol ingested (or 1g/kg). ⎯ Serum methanol level greater than 16 mmol/l (50 mg/dl). ⎯ The slow elimination of methanol during antidote treatment

15. Optic neuritis High dose IV steroids 3 days Oral steroids 1 mg/kg Improvement in visual status Early administration has better prognosis

16. THANK YOU ! A lcohol in any form is injurious to health There is no safe limit