Methanol Eth t yle l ne e G ly l col

Transcription

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2 Methanol Ethylene Glycol

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4 History General Specification Medico legal Importance Digestion and Absorption Breakdown and Removal Alcohol s Acute Effects on the Body Intoxication signs Management Chronic Alcoholism

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6 Low molecular weight No odor (specific odor) Highly soluble in water Absorbed much less in water Pure form transparent, colorless, burning taste Inebriant cerebral neurotoxic poison

7 Manner of poisoning Accidental (child, Mental Retard, ) Suicidal (rare) with other poison Overdrinking Road traffic accidents Industrial accident Problems of marital relationship Violence, Aggregation, Sexual assault

8 Alcohol can be called a food because it contains calories The calories are empty calories and don t contain any Vitamins, minerals, or any other essential nutrients Absorption begins immediately in the mouth Up to 20% can be absorbed directly from the stomach The remainder passes into the small intestine to be absorbed

9 The removal of alcohol from the body begins as soon as the alcohol is absorbed in bloodstream Small amounts leave un-metabolized through sweat, urine, and breath (5-10%) The proportion of alcohol in exhaled air has a constant and predictable relationship to the blood alcohol concentration 1:2100(breathanalyzer) The rate of metabolization is vary from person to person.

10 Sweat glands perspiration 2-6% Kidneys urine 2-4% Lungs expired air 2-4% Liver 90%

11 O 2 P450 Oxygenase NADPH + H+ NADP+ Ethanol Alcohol dehydrogenase Acetaldehyde NAD+ Catalase NADH + H+ H2O2 H2O Peroxisome

12 EtOH Alcohol de Hydrogenase Acetaldehyde Aldehyde de Hydrogenase Acetaldehyde Syndrome Acetate CO2+H2O

13 1 Pint Drunk 1 Pint Drunk Hours Legal Limit Midnight Noon am am am am am pm Healthy individual: Reduction in blood concentration approx 15 mg / 100ml / hour Alcoholic - Reduction? 25mg / 100ml / hour

14 related to V D (volume of distribution) D approximates total body H 2 O 2 Body H 2 O 60% body wt. Eg 83 Kg (B.W. 50L) drinks 5 units = 40 g EtOH (1 uint = 8 g) Blood EtOH = 40g / 50L (40mg / 50 ml) Blood EtOH = 80mg / 100 ml

15 Sex Age Adiposity Smoking Delayed gastric empting Carbonation/Cold drinks Eating Alcohol content of drink Speed of drinking Metabolism General state of health Medication

16 Men and women with same body weight and alcohol intake have different BAC levels, hers will be higher Women contain less water to dilute alcohol During the premenstrual phase of her cycle, a woman absorbs alcohol significantly faster Women on birth control absorb alcohol faster Men have more ADH which accounts for 30% of metabolization of alcohol in men Men do better than women with tasks that involve coordination and motor movement

17 Alcohol is an irritant and promote the flow of gastric juices Moderate drinking has minor effects on circulatory system but does expand surface blood vessels, which accounts for red flush and feeling of warmth Alcohol effects the pituitary gland which tells the kidneys to produce more than normal amounts of dilute urine

18 Beer 3-6% Antiseptic 10-70% Wine 16% Perfume 40-80% Whisky 40% Aftershave 40-80% Vodka 60% Mouthwash 15-25%

19 Loose muscle tone Loss of fine motor coordination Skin cool to the touch (profuse sweating) Eyes (glossy),pupils ( responses) Smell of alcohol on the breath Very poor correlation between the strength of smell and Blood Alcohol Cocentration Staggering drunken gait

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21 < 150 mg% mg% mg% Warmth Well-being Hyper talketive Self-confidence In coordination Decrease reflex Reaction Time Dysartheria Ataxia Diplopia Flushing Sweating Tachycardia Hypothermia Drowsiness Coma Metabolic acidosis Respiratory depression

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23 Supportive care Complete bed rest Other condition look like alcohol intoxication Attention to concomitant» Trauma (head & abdomen)» medication Dextrose 50% Thiamine Folic acid Multi Vitamin Diazepam hemodialysis NO gastric lavage NO Charcoal

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25 Alcohol is the single most important cause of morbidity and mortality from liver disease Cirrhosis Alcoholic hepatitis Fatty liver Abstinence may reverse damage

26 Cardiomyopathy May be reversible Hypertension Cardiac arrhythmias High incidence of sudden death Stroke 4 fold increase

27 Acute alcohol intoxication; depressant Alcohol withdrawal syndrome Impairs thinking and judgment Impairs perceptual skills Impairs motor skills Chronic effects: Amnesia Dementia

28 Wernicke s encephalopathy Korsakoff s psychosis Alcohol-induced dementia Fetal alcohol syndrome

29 Testesteron Ovulation Osteoblast Triglyceride Hypoglycemia Ketoacidosis Mal absorbtion Malnutrition Cardiac abnormalities Pancreatitis Hepatitis Gastritis Neuropsychiatric effect

30 Pleasant experience Magic elixir Reduces tension Helps to handle stress Sexual pleasure Improves social skills Confidence builder Power Aggression

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33 Methanol (methyl alcohol, wood alcohol) is present in many products. Poisoning is uncommon. Ingestion of just 0.15 ml/kg of 100% methanol may cause toxicity. Fatal dose : ml

34 Pediatric cases are usually accidental. Adult cases usually involve suicidal ingestion or ingestion of methanol as an alcohol substitute. Toxic effects are typically severe, if untreated. Death may occur in untreated patients. Inhalation or dermal absorption can produce toxicity. Absorbtion and distribution same as Ethanol

35 Methanol is metabolized by the enzyme alcohol dehydrogenase to formaldehyde, which is then metabolized to formic acid. Retinal toxicity is caused by formic acid accumulation.

36 Methanol Ethanol Alcohol de Hydrogenase Fomepizole Formaldehyde Aldehyde de Hydogenase Formic acid Folic acid Retinal toxicity Metabolic acidosis CO2+H2O

37 30 min- 2 hours Resemble mild ethanol intoxication 6 30 hours Dizziness, drowsiness, vomiting, diarrhea, abdominal pain, ocular sign Incubation Time hours

38 Vital Signs 1. Hyperpnea usually develops to compensate metabolic acidosis. 2. Hypotension may develop late in severe cases. HEENT 1. Blurred, double, or hazy vision begins several hours after ingestion. 2. Constricted visual fields, dilated pupils, hyperemic optic disk and retinal edema, and transient or permanent blindness may develop.

39 Gastrointestinal 1. Nausea & vomiting 2. Abdominal pain Renal 1. Hematuria 2. Acute renal insufficiency Neurologic 1. The earliest sign is inebriation, which progresses to ataxia, seizures, and coma in severe cases. 2. Parkinsonism may develop as a sequelae of severe intoxication.

40 Essential Tests: 1. Serum electrolytes (Hyperkalemia) 2. BUN and creatinine 3. Glucose (Hyperglycemia) 4. Arterial blood gases Elevated anion gap metabolic acidosis supports the diagnosis. 5. Serum methanol level (greater than 20 mg/dl)

41 Recommended Tests: 1. Serum ethanol level 2. Serum acetaminophen and aspirin levels 3. Head CT 4. Lumbar puncture and cultures may be performed in patients with altered mental status, headache, seizure or fever.

42 Supportive care Antidotes Ethanol Fomepizole Sodium bicarbonate Hemodialysis Folic acid

43 Indications : History of possible methanol ingestion. Clinical evidence of toxicity. Serum methanol level greater than 20 mg/dl. It may be used if fomepizole is not available.

44 Loading dose Gram/kg of Ethanol 10% (Oral) Non-drinker/child 0.8 Average drinker 1.4 Chronic drinker 2 Maintenance Dose (MD) 100 mg /kg /hour of Ethanol 10% (Oral) Increase M.D. 2-3 times during hemodialysis Ethanol concentration: mg%

45 Methanol level > mg/dl Severe metabolic acidosis not respond to treatment Renal failure Ocular signs Coma Pulmonary edema

46 Folate or Leucovorine (tetrahydrofolate) to hasten elimination of formic acid. Leucovorin 1mg/kg Max 50 mg/dose/iv/4-6 hours until methanol becomes undetectable. Folate 1mg/kg Max 50 mg/dose/p.o/4-6 hours until methanol becomes undetectable.

47 Full recovery if appropriate management is initiated before severe effects develop. Permanent visual deficits may develop. Parkinsonism occurs rarely, associated with basal ganglia infarcts. Polyneuropathy occurs rarely.

48 Asymptomatic patients may be discharged when the following conditions are met: Normal electrolytes, BUN, and creatinine Norma ABG Serum ethanol and methanol levels of zero

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50 Ethylene glycol is a sweet, odorless and colorless liquid. It is a common component of antifreeze used in: Heating and cooling systems Inks Brake Fluid

51 It is used as an industrial solvent in: Paints Plastics It is used in synthesis of: Resins Synthetic Fibers Waxes

52 Poisoning is uncommon. Death occurs in patients who do not receive medical care. Poisoning most commonly occurs: Accidental ingestion Suicidal Attempt

53 ADH Ethylene Glycol Glycoaldehyde Glyoxalate ADH Pyridoxine Oxalate Glycine Ethylene Glycol is non-toxic Toxicity being to

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55 The first phase : 3 min 12 hours Resemble ethanol intoxication without alcohol smell Nausea, Vomiting & hematemesis The major effects are on the CNS Coma Seizure Nystagmus

56 The second Phase: hours Tachycardia Mild Hypertension Pulmonary edema CHF Due to deposition of calcium oxalate within the vascular tree, myocardium and lung parenchyma

57 The third phase: hours Flank pain Causto Vertbral Angle (CVA) Tenderness Acute tubular necrosis

58 Serum ethylene glycol level Levels should be obtained in all patients with a history of ingestion. Level > 20 mg/dl is an indication for fomepizole or ethanol therapy. Level > mg/dl is an indication for hemodialysis.

59 Serum electrolytes, BUN, creatinine ABG Elevated anion gap metabolic acidosis supports the diagnosis. Urinalysis with microscopic examination The presence of calcium oxalate crystals with a history of ingestion or metabolic acidosis is strong evidence of poisoning. The absence of crystals does not exclude the diagnosis.

60 Focus treatment: Supportive care Treatment with fomepizole Treatment with ethanol Hemodialysis as indicated.

61 Indications History of possible ethylene glycol ingestion Evidence of toxicity Serum ethylene glycol level above 20 mg/dl Contraindications Allergic response to fomepizole

62 Indications Fomepizole is not available. If levels are not immediately available, therapy should be instituted if there is: A reliable history of significant ingestion Unexplained anion gap acidosis

63 Pyridoxine and thiamine to hasten elimination of toxic ethylene glycol metabolites. Pyridoxine Dose 1 to 2 mg/kg administered intravenously every 6 hours until ethylene glycol level is undetectable.

64 Thiamine Dose Adult dose is 100 mg/i.v. over 5 minutes every 6 hours until ethylene glycol level is undetectable. Pediatric dose is 50 mg/i.v. over 5 minutes every 6 hours until ethylene glycol level is undetectable. Sodium Bicarbonate Sodium bicarbonate should not be used routinely but may be used as a temporarily for lifethreatening acidosis prior to hemodialysis.

65 Hemodialysis is recommended Ethylene glycol level > mg/dl Severe metabolic acidosis not respond to treatment Renal failure Mental status changes

66 Asymptomatic patients Serum ethylene glycol levels < 20 mg/dl No anion gap metabolic acidosis Stable renal function

67 History of possible methanol ingestion. Clinical evidence of toxicity. Serum methanol level greater than 20 mg/dl.

68 Allergic reaction to fomepizole Metronidazole GI ulceration Child < 5 years Severe hepatic disease

69 Loading Dose : 15mg/kg (IV) Maintenance Dose : 10 mg/kg/12h for 4 doses then 15mg/kg/12h Each dose is diluted in 100 ml normal saline or D5W and infused over 30 minutes.

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