Dr. Ali Mohammad Ali Mohammadi FORENSIC MEDICINE AND TOXICOLOGY . METHANOL POISONING Dr. Ali Mohammad Ali Mohammadi FORENSIC MEDICINE AND TOXICOLOGY .

MECHANISM OF ACTION METHANOL FORMALDEHYDE FORMIC ACID ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE METHANOL FORMALDEHYDE FORMIC ACID METHANOL ITSELF NOT TOXIC. FORMALDEHYDE VERY TOXIC, BUT VERY RAPIDLY METABOLISED TO FORMIC ACID. FORMIC ACID RESPONSIBLE FOR THE TOXICITY RELATED TO METHANOL INGESTIONS

MECHANISM OF ACTION OCULAR TOXICITY CIRCULUS HYPOXICUS METHANOL OCULAR TOXICITY FORMALDEHYDE INHIBITION OF MITOCHONDRIAL RESPIRATION INCREASED FORMIC ACID TOXICITY FORMIC ACID CIRCULATORY FAILURE CIRCULUS HYPOXICUS TISSUE HYPOXIA ACIDOSIS ACIDOSIS LACTIC ACID PRODUCTION Early stage of poisoning GENERAL TOXICITY

SIGNS AND SYMPTOMS INITIAL INEBRIATION - ESPECIALLY IF ETHANOL COINGESTED AFTER 12 - 24 HOUR DELAY - PROGRESSION TO ACIDOSIS AND OTHER SIGNS AND SYMPTOMS MAY BE FURTHER DELAY WITH CONTINUED INGESTION OF ETHANOL

SIGNS AND SYMPTOMS CNS - INEBRIATION PROGRESSING TO COMA, CONVULSIONS RETINAL - BLURRED VISION, PHOTOPHOBIA, VISUAL ACUITY LOSS, DILATED NON-REACTIVE PUPILS, OPTIC NERVE HYPERAEMIC - BECOMING OEDEMATOUS GIT - NAUSEA, VOMITING CARDIAC - TACHYCARDIA, HYPERTENSION PROGRESSING TO HYPOTENSION AND CARDIOGENIC SHOCK RESPIRATORY - TACHYPNOEA

INVESTIGATION BLOOD METHANOL LEVEL! ABG - METABOLIC ACIDOSIS OSMOLAL GAP - INCREASED (METHANOL) ANION GAP - INCREASED (FORMIC ACID, LACTIC ACID) BLOOD ETHANOL MAGNESIUM, AMYLASE, POTASSIUM

Lab ABG – metabolic acidosis Creatinine, BUN & lytes – increased anion gap Increased Osmolal gap Osmolal gap = measured osmolality – calculated osmolality Calculated osmolality = 2 x Na + glucose in mm/L + BUN in mm/L + Ethanol in mm/L

Osmolal Gap cont’d Can’t tell whether toxic alcohol is Methanol, Ethanol, Ethylene Glycol or Isopropyl Alcohol Only increased by parent alcohols therefore not good for late presentation

TREATMENT HAZARD ASSESSMENT ABC’s TOXICOKINETICS ABSORPTION DISTRIBUTION METABOLISM ELIMINATION TOXICODYNAMICS SUPPORTIVE CARE

TREATMENT CORRECTION OF METABOLIC ACIDOSIS BICARBONATE (AGGRESSIVE TREATMENT) CAN REVERSE VISUAL IMPAIRMENT REDUCES MOVEMENT OF FORMATE TO THE CNS MAY REQUIRE 400 TO 600 MMOL DURING FIRST FEW HOURS REHYDRATION

MECHANISM OF ACTION METHANOL FORMALDEHYDE FORMIC ACID ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE METHANOL FORMALDEHYDE FORMIC ACID

MECHANISM OF ACTION X METHANOL ETHANOL ALDEHYDE ACETIC ACID FORMALDEHYDE FORMIC ACID ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE ETHANOL ALDEHYDE ACETIC ACID

(REDUCES FORMATION OF TOXIC METABOLITES) TREATMENT ETHANOL (REDUCES FORMATION OF TOXIC METABOLITES) MAINTAIN BLOOD ETHANOL LEVEL OF 100 - 150 mg/dl LOADING DOSE BEWARE OF EXISTING ETHANOL LEVEL MAINTENANCE DOSE TITRATED AGAINST RATE OF ELIMINATION NON-ALCOHOLIC 15 - 20 mg/dl/h CHRONIC ALCOHOLIC 30 - 40 mg/dl/h CHILD 30 mg/dl/h

TREATMENT ETHANOL INDICATIONS BLOOD METHANOL LEVELS GREATER THAN 6.25 mmol/l (20 mg/dl) IF HAEMODIALYSIS IS TO BE COMMENCED

TREATMENT ETHANOL HALF LIFE OF METHANOL IS USUALLY 15 - 30 HOURS HALF LIFE OF METHANOL WITH ETHANOL TREATMENT IS 45 - 50 HOURS YOU MAY THEREFORE HAVE A NON-SOBER PATIENT ON THE WARD FOR SEVERAL (4 - 5) DAYS...

TREATMENT HAEMODIALYSIS METHANOL LOW MOLECULAR WEIGHT NOT PROTEIN BOUND LOW VOLUME OF DISTRIBUTION THEREFORE IDEAL FOR HAEMODIALYSIS

TREATMENT HAEMODIALYSIS INDICATIONS ANY DEGREE OF VISUAL IMPAIRMENT SEVERE METABOLIC ACIDOSIS BLOOD METHANOL LEVEL GREATER THAN 15 mmol/l (50mg/dl)

METABOLISM METHANOL FORMALDEHYDE FORMIC ACID CO2 and H2O ALCOHOL DEHYDROGENASE ALDEHYDE DEHYDROGENASE METHANOL FORMALDEHYDE FORMIC ACID FOLIC ACID THF MAGNESIUM CO2 and H2O

TREATMENT FOLINIC ACID/FOLIC ACID 50 mg IV EVERY FOUR HOURS FOR 24 HOURS, OR WHILE FORMIC ACID MAY STILL BE ACCUMULATING MAGNESIUM MgSO4 TITRATED AGAINST BLOOD MAGNESIUM LEVELS

METHYLATED SPIRITS METHYLATED SPIRITS IS 5% METHANOL, 95% ETHANOL ACUTE INGESTION PRESENTS AS ETHANOL, RATHER THAN METHANOL, POISONING METHANOL INTOXICATION IS ONLY A CONCERN IF METHYLATED SPIRSTS IS INGESTED CHRONICALLY

METHYLATED SPIRITS EXAMPLE IF 250 ml METHYLATED SPIRITS INGESTED: BLOOD ETHANOL LEVEL = 450 mg/dl (LD50) BLOOD METHANOL LEVEL = 24 mg/dl

METHYLATED SPIRITS EXAMPLE IF 1.5 l METHYLATED SPIRITS INGESTED OVER SEVERAL DAYS: BLOOD ETHANOL LEVEL ~ 450 mg/dl (LD50) BLOOD METHANOL LEVEL = 142 mg/dl (IN 12 HOURS ETHANOL LEVEL = 100 mg/dl METHANOL LEVEL = 124 mg/dl)