Alcohol intoxication & withdrawal

ALCOHOL INTOXICATION AND WITHDRAWAL

1. ALCOHOL INTOXICATION AND WITHDRAWAL DR. PREM MOHAN JHA JR3 , P.G. DEPTT. OF MEDICINE. S.N.M.C., AGRA

2. INTRODUCTION The harmful use of alcohol results in 2.5 million deaths each year . 320,000 young people between the age of 15 and 29 die from alcohol-related causes, resulting in 9% of all deaths in that age group . Global Status Report On Alcohol 2004, Geneva, WHO.

3. ACUTE ETHANOL INTOXICATION Legal limit for intoxication - 80mg/ dL Odor threshold - 10 ppm

4. ABSORPTION Stomach (70%), D uodenum (25%) Mouth and Esophagus (small amounts) European journal of internal medicine 19 (2008) 561-567 .

5. DISTRIBUTION& ELIMINATION Distributed to almost every tissue. Vd =0.5 l/kg. Half life = 2 – 6 hr . Ethanol A cetadehyde+NADH +NAD Acetate CO2+H2O Acetyl coA Clin J Am Soc Nephrol 3 (2008) 208-225

6. CLEARANCE 15 – 18 mg/ 100 ml blood/ hr. Zeero order kinetics. I ndependent of alcohol conc. 2 – 10 % is excreted directly through the lungs, urine, or sweat, but T he greater part (90 – 95%) is metabolized ( oxidised ) to acetaldehyde, primarily in the liver. Blood levels of ethanol are expressed as milligrams or grams of ethanol per deciliter (e.g., 100 mg/ dL = 0.10 g/ dL ) Values of 0.02 g/ dL resulting from the ingestion of one typical drink . Harrisons principles of internal medicine, 18 th ed , vol.2

7. PATHOPHYSIOLOGY Stimulate GABA A recepto ↑NAD/NAD ratio. ↑ ketogenesis . ↓gluconeogenesis ↑ glycogenolysis Fluid & electrolyte imbalance. Harrisons principles of internal medicine, 18 th ed , vol.2

8. Effects of Blood Alcohol Levels in the Absence of Tolerance Blood Level, g/ dL USUAL EFFECT O.O2 Decreased inhibitions, a slight feeling of intoxication 0.08 Decrease in complex cognitive functions and motor performance 0.20 Obvious slurred speech, motor incoordination, irritability, and poor judgment 0.30 Light coma and depressed vital signs 0.40 Death Harrisons principles of internal medicine, 18 th ed , vol.2

9. SIGNS THAT IMMEDIATE MEDICAL ATTENTION IS NEEDED Nervous system depression (sleepiness, coma, lethargy, and decreased response to pain) Withdrawal accompanied by pain Digestive problems that include vomiting, bleeding, and dehydration Slow or absent breathing Grand mal seizures Delirium tremens Disturbances of vision, mental confusion, and muscular incoordination Disinterested behavior and loss of memory European journal of internal medicine 19 (2008) 561-567.

10. ASSCOCIATED ACUTE PROBLEMS Alcoholic ketoacidosis. Alcoholic hypoglycemia. Fluid & electrolyte imbalance. Wernicke’s encephalopathy. Acute effects on heart . Acute GI efects . Acute alcoholic myopathy . Trauma Associated other substance poisoining . European journal of internal medicine 19 (2008) 561-567.

11. Alcoholic ketoacidosis: High anion gap acidosis Normal or low glucose level Chronic alcoholics Binge drinking weeks before symptoms Dehydration, starvation due to vomiting ,gastritis Clin J Am Soc Nephrol 3 (2008) 208-225

12. Alcohol P oor food intake D ehydration ↓ ↓ ↓ Acetaldehyde glycogenolysis ↑counter regulatory ↓ hormones Acetate ↓ ↓ ↓ ↑NADH/NAD ↑Glucagon ratio ↓ I nsulin ↓gluconeogenesis KETOGENESIS Clin J Am Soc Nephrol 3 (2008) 208-225

13. Altered mental status Kussumal breathing Ketotic breath Lab finding high anion gap acidosis ↑beta hydroxybutyrate:acetoacetate ↓insulin level Exclude other causes of ↑metabolic acidosis . Clin J Am Soc Nephrol 3 (2008) 208-225 Alcoholic ketoacidosis:

14. ALCOHOLIC HYPOGLYCEMIA Chronic “street alcoholic” found unresponsive Symptoms Neuroglycopenic → confusion,fatigue,seizure , Loss of consciousness→death Autonomic responses → palpitation ,tremor , sweating Signs Pallor ,diaphoresis Tachycardia,raised systolic B.P Transient focal neurological signs European journal of internal medicine 19 (2008) 561-567 .

15. “all alcoholics are dehydrated” is false. Immediate ↑ in urine volume followed by ↑ADH. Hydration also depends on - diet,nonalcoholic fluids,type of drinks -vomiting, diarrhea,infection Water intoxication & hyponatremia in severe chronic alcoholics→seizure & altered sensorium Central pontine mylenolysis WATER AND ELECTROLYTES DISORDERS Clin J Am Soc Nephrol 3 (2008) 208-225

16. Other electrolytes abnormalities Hypomagnesemia Hypophosphatemia Hpokalemia Hypocalcemia Clin J Am Soc Nephrol 3 (2008) 208-225 WATER AND ELECTROLYTES DISORDERS

17. As high as 12.5% in alcoholics. Major reversible cause of death. If untreated 10-20% mortality rate. Thiamine deficiency is the root cause. Magnesium deficiency in thiamin resistant cases. Clinical features G lobal confusion O cular abnormalities A taxia WERNICKE-KORSAKOFF’S SYNDROME European journal of internal medicine 19 (2008) 561-567 .

18. ACUTE EFFECT ON HEART Direct negative inotropic effect & vasodilation. PR & QT prolongation Both supraventricular & venntricular arrythmia . “holiday heart syndrome” Various degree of heart block. + ve correlation between and sudden cardiac death. European journal of internal medicine 19 (2008) 561-567.

19. ACUTE ALCOHOLIC MYOPATHY Acute muscle necrosis mainly in binge drinkers Alcoholism is the most common cause of rhabdomyelisis Raised CKMM,myoglobinuria , Acute tubular necrosis →↑urea , creatinine Conservative management European journal of internal medicine 19 (2008) 561-567 .

20. ACUTE GASTROINTESTINAL EFFECT Acute gastritis & esophagitis. Epigastric distress and gastrointesinal bleeding. Mallory- weiss tear. Acute hepatitis & pancreatitis. European journal of internal medicine 19 (2008) 561-567 .

21. Toxic Metabolic Infectious diseases Neurologic Trauma Miscellaneous. DIFFERENTIAL DIAGNOSIS IN ACUTELY INTOXICATED PATIENT. European journal of internal medicine 19 (2008) 561-567.

22. DIAGNOSIS HISTORY Quantity of alcohol consumed Type of beverage Time course of symptoms Circumstances Eventual injuries PHYSICAL EXAMINATION Vital signs Nutritional status Hydration Alcoholism related signs e.g. capillary prominence,spider naevi , telengiectasias , palmar erythema, muscular atrophy European journal of internal medicine 19 (2008) 561-567.

23. LAB INVESTIGATIONS BAC (blood alcohol conc.) – most imp. Serum osmolality – increases Sodium, potassium, calcium B. urea nitrogen, B. sugar, A mylase, European journal of internal medicine 19 (2008) 561-567. LFT, ABG, Urine/blood ketones, ECG, CXR-PA, CT Head when head trauma suspected

24. TREATMENT Airway assessment Breathing Circulation IV assess Rules tube, Propped Up Position – to avoid aspiration. Foleys catheterisation Thiamin 100 mg im / iv stat. Mechanical ventilation if required . European journal of internal medicine 19 (2008) 561-567 .

25. IV solution containing : 1 ltr 0.45% DEXTROSE NORMAL SALINE,2 gm MAGNESIUM SULPHATE, 1 mg FOLATE, 100 mg THIAMINE. Antiemetic drugs Sedatives – agitated, violent pt Droperidol , haloperidol Physical restrains- used only in extreme conditions Mechanical ventilation & intensive care European journal of internal medicine 19 (2008) 561-567. TREATMENT contd …

26. METADOXINE is the one specific drug that is useful in tt of acute alcohol intoxication It fascilitate atp synthesis and prevent decrease in atp in both brain and liver Single iv injection of 900 mg significantly decreases half life of ethanol in blood. Medial time of recovery is around 1 hr. European journal of internal medicine 19 (2008) 561-567. TREATMENT contd …

27. M E T H A N O L P O I S O N I N G

28. TOXICOKINETICS ABSORPTION Most of the cases of methyl alcohol intoxication occur through oral ingestion intentionally or accidently (half life – 5 mints). Peak absorption occuring b/w 30 – 60 mints. Other routes of absorption are through intact skin, inhalation etc. DISTRIBUTION Rapid distribution results in peak plasma conc within 30 – 60 mints. American Academy Of Clinical Toxicology,40(4), 415-446, (2002

29. METABOLISM Methanol + NAD+ Formaldehyde + NADH ( alcohol dehydrogenase) Formic acid ( folate ) CO2 + H2O American Academy Of Clinical Toxicology,40(4), 415-446, (2002

30. CLINICAL FEATURES Inebriated but lack of euphoria. 40 minutes --- 72 hrs of latent period. Fatal dose 60-240 ml. Signs and symptoms are mainly limited to CNS, EYE & GIT. Vertigo, light headedness, dyspnea , agitation. N ausea, vomiting, diarrhea, abdominal pain (d/t developement of acute pancreatitis), Blurred vision, photophobia, ↓ visual acuity. American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

31. CLINICAL FEATURES contd … Blurred vision with relatively clear sensorium strongly suggest methanol intoxication, but Absense of symptoms and clear sensorium does not rule out serious toxicity. CO-ingestion of ethanol typically delays symptoms beyond 24 hrs. BRADYCARDIA, BLINDNESS, SEIZURES, PROLONGED COMA, SHOCK, PERSISTANT ACIDOSIS & ANURIA ARE SERIOUS PROGNOSTIC SIGNS . American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

32. Physical examination C onstricted visual field, Fixed & dilated pupils, Retinal edema &hyperemia of disk Opisthotonus Respiratory failure / arrest is the main cause of death. CLINICAL EFFECTS contd … American Academy Of Clinical Toxicology,40(4), 415-446, (2002

33. LAB FINDING High anion gap M etabolic acidosis High osmolar gap Strongly suggest methanol toxicity. American Academy Of Clinical Toxicology,40(4), 415-446, (2002

34. ROUTINE LAB FINDING S. methanol & ethanol conc. S. Electrolytes including calcium. S. BUN S. creatinine CBC URINE- routine, microscopy and for ketones. SGOT / SGPT S. Amylase ABG American Academy Of Clinical Toxicology,40(4), 415-446, (2002

35. IMAGING STUDIES B/L NECROSIS OF PUTAMEN is the most consistent radiographic finding following severe methanol toxicity. Marked cerebral edema Persistant of occipital lesions in cerebral cortex on repeat MRI after 1 month suggests that visual impairement is permanent. American Academy Of Clinical Toxicology,40(4), 415-446, (2002

36. MANAGEMENT

37. American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

38. American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

39. TREATMENT contd …. Aggressive tt of acidosis by sodabicarbonate . Ethanol Achieve BAC of 100- 150mg /100ml Loading 0.8gm/ kg of 5 – 10% ethanol Followed by 130mg/kg/hr. Oral loading if no iv preparation If dialysis,250-350 mg/kg/hr. American Academy Of Clinical Toxicology,40(4), 415-446, (2002)

40. Folic acid : 30 mg iv every 4 hrly Leucovorin : 1-2mg/kg iv F omepizole : 15-20 mg/kg iv Haemodialysis ( not haemoperfusion ) HAEMODIALYSIS INDICATIONS: Methanol>20-50mg/100ml Acidosis not responsive to bicarbonate Formate levels > 20 mg/100ml Visual impairment Renal impairement Dialysis till methanol level ≈0mg/100ml and acidosis clears . American Academy Of Clinical Toxicology,40(4), 415-446, (2002

41. WITHDRAWAL SYNDROME Results from Ethanol intake reduction NOT necessarily result of complete withdrawal

42. INTRODUCTION Usual time from last drink is about 5 days but can last upto 14 days. Do not treat alcohol withdrawal with more alcohol. American family physician .march (2004), vol . 69 (6),1448.

43. American family physician .march (2004), vol . 69 (6),1448.

44. Australia government deptt of health and aging guidelines

45. American family physician .march (2004), vol . 69 (6),1448.

46. ASSESSMENT OF SEVERITY SIWA- Ar scale Score <9 - Mild 9 – 15 - Moderate >15 - Severe withdrawal American family physician .march (2004), vol . 69 (6),1448.

47. American family physician .march (2004), vol . 69 (6),1448.

48. American family physician .march (2004), vol . 69 (6),1448.

49. American family physician .march (2004), vol . 69 (6),1448.

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