Toxic alcohol

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Toxic alcohol

  1. 1. Toxic Alcohol Thitisak Kitthaweesin, M.D. Department of Medicine Phramongkutklao Hospital and College of Medicine
  2. 2. Osmolal Gap Osmolal Gap = Measured Serum Osmol – Calculated Serum Osmol Normal Osmolal gap < 10 mOsm/L High Osmolal gap > 20 mOsm/L
  3. 3. Alcohol Ethanol Isopropanol Methanol Ethylene glycol
  4. 4. Ethanol Isopropanol Ethylene glycol MethanolCOMMON SEVERITYEthanol Isopropanol Ethylene glycol Methanol
  5. 5. Ethanol Methanol Isopropanol Ethylene glycolCOMMON SEVERITYEthanol Isopropanol Ethylene glycol Methanol
  6. 6. Effect of Alcohol on SerumOsmolality Compound Molecular Weight ∆Sosm(mOsm/L) per 10 mg/dL ∆Serum Alcohol Concentration Methanol 32.04 3.09 Ethanol 46.07 2.12 Isopropanol 60.02 1.66 Ethylene glycol 62.07 1.60 Propylene glycol 76.09 1.31 Diethylene glycol 106.12 0.90
  7. 7. Kinetics of Major AlcoholsAlcohol Vd (L/kg) Half-Life (h) Route of Elimination (%) Alone With Liver Lung Renal EthanolEthanol 0.5 2-6 95 2 3Methanol 0.6-0.7 14-30 43-96 97 2.5 1Ethylene 0.5-0.8 3-8 17-18 80 - 20glycolDiethylen 0.5 4-6 ?> 30-50 - 50-70e glycolPropylen 0.5 1.4-3.3 17 55-5 - 25-45e glycolIsopropa 0.5 2.5-6.4 ? 80-90 - 10-20nol
  8. 8. EthanolMost commonly ingested alcohol
  9. 9. Ethanol Sources  Alcoholicdrinking  Mouthwashes  Colognes  Medical preparations
  10. 10. Pathophysiology CNS depression : inhibit neuronal activity Cross-tolerance exists : ethanol + sedative drugs (benzodiazopine, barbiturates) Absorption : Proximal small bowel > stomach, large bowel > mouth, esophagus Gender-relate differences Excretion : lungs, urine, sweat
  11. 11. Ethanol Metabolism
  12. 12. Ethanol Intoxication Slurred speech Disinhibited behavior CNS depression Decreased motor coordination and control Hypotension
  13. 13. Ethanol level > 50 mg/dL
  14. 14. The maximum blood alcohollevel limit for drivers
  15. 15. Symptoms• depend on both the serum concentration and individual ethanol metabolism Serum ethanol level Symptoms less than 25 mg/dL warmth and well-being. 25-50 mg/dL. Euphoria and decreased judgment 50-100 mg/dL. Incoordination, decreased reaction time/reflexes 100-250 mg/dL Cerebellar dysfunction (ie, ataxia, slurred speech, nystagmus) greater than 250 mg/dL Coma greater than 400 mg/dL respiratory depression, loss of protective reflexes, and death
  16. 16. Ethanol Withdrawal Palpitation Autonomic hyperactivity Sinus tachycardia Seizure Maximal symptom occur in 48 hrs.
  17. 17. Treatment Observation Hypoglycemia should be excluded Thiamine Activated charcoal (ineffective)
  18. 18. Alcoholic Ketoacidosis (AKA)
  19. 19. Epidemiology Uncommon in patients with acute ethanol intoxication Most frequent in patients who have long term ethanol intake, liver disease and develop syndrome after period of a binge drinking Associated with reduced food intake, vomiting Mortality is low 1%
  20. 20. Pathophysiology  Precursor of ketone  Ketogenesis attributed to lipolysis, FFA generation from low insulin level and increased level of epinephrine, cortisol, glucagon  Excess production of acetoacetic acid and β-hydroxybutyric acid
  21. 21. Clinical Findings Abdominal pain Nausea, vomiting Altered mental status
  22. 22. Laboratory Findings Metabolic acidosis ,usually wide AG Mixed acid-base disorders HCMA is uncommon Hyponatremia, hypokalemia, hypophosphatemia Serum osmolality often normal Elevated sOsm from elevated serum ethanol or ketone Serum ethanol level often undetectable Blood glucose low, normal or high
  23. 23. Treatment Resolution of AKA occurs after administration of dextrose and/or saline Restore volume deficit and provide glucose to prevent hypoglycemia
  24. 24. IsopropanolIsopropanol ( CH3CHOHCH3) Isopropyl 2-propanol
  25. 25. Isopropanol(Isopropyl Alcohol) Second most commonly ingested alcohol Severity : methanol, ethylene glycol > isopropanal > ethanol
  26. 26. Sources Industry solvent Disinfectant Skin and hair products Jewelry cleaners Detergents Paint thinners Antifreeze
  27. 27. Pathophysiology Clear, burning taste and aromatic odor Rapidly absorb within 30 minutes Complete absorption within 2 hrs. Excretion : kidney 20- 50% Metabolism pathway
  28. 28. Isopropanol Metabolism NAD+ NADH+H+Isopropanol Acetone
  29. 29. Toxic dose 70% isopropanol 0.5 ml/kg : Symptom 1.0 ml/kg : Toxic dose 2-4ml/kg : Lethal dose (Report 1 liter survival) Children swallow 3 times : Symptom
  30. 30. Clinical Features Symptoms familiar with ethanol But occur in long duration toxication and CNS depression Nystagmus, coma, respiratory depression and hypotension
  31. 31. Lab High osmolal gap Ketosis Without wide AG metabolic acidosis
  32. 32. Laboratory Facts Serum level 60 mg/dL increase serum osmolarity 10 mOsm/kg Acidosis is rare : parent and metabolite are not organic aicd High serum or urine acetone level without acidosis is suggestive of recent isopropanol ingestion Renal failure in setting of significant hypotension Hypoglycemia : result from interference of gluconeogenesis by isopropanol
  33. 33. Treatment Supportive treatment Inhibition of alcohol dehydrogenase is not indicated because acetone is less toxic than isopropanol Hemodialysis  Isopropanol level > 400 mg/dL  Significant CNS depression, renal failure or hypotension If acidosis is significant  investigate for other cause
  34. 34. MethanolMethanol (CH3OH) or Methylalcohol Wood spirits Wood alcohol
  35. 35. Sources Shellacs, varnishes, paint removers Windshield washing fluids and antifreeze formulations Contaminated whiskey Accidental ingestion Suicidal
  36. 36. Character Colorless Volatile liquid Distinctive odor Rapid absorption Minimum lethal dose for adults is 10 mL
  37. 37. Pharmacokinetics MW 32 g/mol Vd 0.6 L/kg Rapid absorption after ingestion Peak 30-90 min Highest concentration at kidney, liver and G.I. tract Vitreous humor, optic nerve : high level Elimination half-life 14-18 hr without treatment Excretion : 90-95% by liver 2-5% by renal Other by respiratory system
  38. 38. Metabolism of Methanol
  39. 39. Clinical Features Onset may be delayed Early: mucosal irritation, N/V, abdominal pain Late : CNS depression, No early phase of elation Visual disturbances (looking into snow field) Wide anion gap metabolic acidosis
  40. 40. Symptomatology Early period  CNS depression  Effect of methanol before metabolized Latent period  Accumulation of formate  Last 14-18 hr  Followed by systemic findings
  41. 41. Diagnosis of methanol poisoning History Wide anion gap metabolic acidosis and osmolar gap DDx.  Ethylene glycol, DKA, Paraldehyde, Isoniazid, Salicylates, Iron, Lactic acidosis, Phenformin, Uremia
  42. 42. Methanol blood concentration mg/dL  normal methanol blood concentation from endogenous sources mg/dL  Asymptomatic mg/dL  Serious poisoning - mg/dL  Risk of fatality
  43. 43. Systemic Findings Metabolic acidosis CNS effects Ocular findings Other
  44. 44. Systemic Findings Metabolic acidosis  pH < 7.0 strongest predictor of mortality  Mortality increased 20 times pH <7.0 Vs >7.0 CNS effects  Headache  Lethargy, delirium  Convulsion, coma…increased mortality 10 times
  45. 45. Systemic Findings Ocular findings  Direct cytotoxic effect of formate on retina  Photophobia  Central scotoma  Visual field defects  Fixed pupils and difficulty with light adaptation  Pupillary dysfunction : strong predictor of mortality  Fundoscopic signs : hyperemia, disk edema, possible optic atrophy
  46. 46. Systemic Findings Other findings  Nausea, vomiting  Diaphoresis  Abdominal pain  Pancreatitis
  47. 47. Diagnosis of methanol poisoning History Wide anion gap metabolic acidosis and osmolar gap DDx.  Ethylene glycol, DKA, Paraldehyde, Isoniazid, Salicylates, Iron, Lactic acidosis, Phenformin, Uremia
  48. 48. Anion Gap High anion gap metabolic acidosis  Formate accumulation  Lactate production  Early or later after co-ingestion with MetOH+EtOH may have little or no acidosis
  49. 49. Osmolar Gap Methanol produce osmolar gap  Serum level 32 mg/dL increased measured serum osmolarity 10 mOsm/kg Normal osmolar gap <10 mOsm/kg  Present later after ingestion and methanol converted to formate  Formate not contribute to serum osmolarity because it is balanced by sodium
  50. 50. Methanol blood concentration mg/dL  normal methanol blood concentation from endogenous sources mg/dL  Asymptomatic mg/dL  Serious poisoning - mg/dL  Risk of fatality
  51. 51. Treatment Take BS, BUN, Cr, methanol, ethanol level Glucose + Thiamine + Naloxone Supportive care Correction of acidosis : NaHCO Administration of fomepizole or ethanol Dialysis
  52. 52. Ethanol Indication  Plasma level > 20 mg/dL  Recent history of methanol ingestion with serum osmolal gap > 10 mOsm/L  Strong clinical suspicion of methanol poisoning with at least two of the following  Arterial pH < 7.3  Serum HCO3- <20 mEq/L  Osmolal gap > 20 mOsm/L AACT Recommendation, 2002
  53. 53. ManagementLoading dose : . - . g/kgoral or I.V. ( Alcoholism mg/kg )Maintenance : . g/kg/hr. ( Hemodialysis  .g/kg/hr.)
  54. 54. Hemodialysis Indication  50 mg/dL Methanol level  Methanol consumed 30 mL  Severe metabolic acidosis or high formate level  Visual, fundoscopic or CNS disturbance
  55. 55. Ethylene glycol
  56. 56. Source Coolant (antifreeze) Preservative Glycerine substitute
  57. 57. Character Colorless, odorless, sweet taste Rapidly absorbed : ingestion Not by lungs, skin
  58. 58. Metabolism ADH ALDH Folate Methanol Formaldehyde Formic acid CO2+H2O ADH ALDH Ethylene glycol Glycoaldehyde Glycolic acid Thiamine Glyoxylic acid Pyridoxine, Mg++ Glycine+Benzoic acidα-hydroxy-β-ketoadipic acid Oxalic acid Hippuric acid
  59. 59. Clinical features 3 Phases Phase 1: - hrs.  Slurred speech and ataxia. But without the odor of ethanol on their breath Phase 2: - hrs.  Cardiopulmonary, CHF, ARDS Phase 3 : - hrs.  Nephrotoxicity, oligulic renal failure, ATN
  60. 60. Renal Toxicity Direct toxic effect from metabolites of ethylene glycol Hydronephrosis and obstruction from calcium oxalate crystal Most renal damage is reversible Renal recovery may take a few month
  61. 61. Laboratory Wide AG metabolic acidosis Calcium oxalate crystalluria Acute renal failure Hypocalcemia High osmolal gap*
  62. 62. Calcium oxalate crystal Monohydrate form  Dihydrate form  Dumbbell shape  Octahedral shape  More common  More specific  Ingestion of high  Require higher vitamin C and high oxalate concentration urate-containing food for its formation  More indicative of intoxication
  63. 63. Calcium oxalate crystal
  64. 64. Treatment Supportive treatment Airway protection Circulatory support Correction of metabolic abnormalities Control seizure
  65. 65. Treatment No role for activated charcoal, cathartics or gastric lavage Asymptomatic hypocalcemia  Risk of ↑ formation of calcium oxalate crystal Alcoholic persons and malnourished should be given thiamine and pyridoxine
  66. 66. Antidote Indication  Plasma concentration > 20 mg/dL  Recent ingestion and Osmolar gap > 10 mOsm/kg or high clinical suspicion  AND 2 of the followings  pH < 7.3  Serum bicarbonate < 20 mmol/L  Osmolar gap > 10 mOsm/kg  Urinary oxalate crystals
  67. 67. Antidote  Ethanol  FDA not approved  Loading dose 0.6 g ethanol/kg  Constant infusion to keep blood alcohol level 100-200 mg/dL  Average maintenance dose 100 mg/kg/hr  Blood alcohol checked every 1-2 hr until steady state then 2-4 hr
  68. 68. Antidote  Fomepizole  FDA approved  Loading dose 15 mg/kg  Followed bt 10 mg/kg every 12 hr for 48 hrs  After 48 hrs, 15 mg/kg every 12 hr  Continued until serum ethylene glycol level < 20 mg/dL, asymptomatic and normal pH  In dialysis, fomepizole need to be dosed every 4 hr
  69. 69. Hemodialysis Indication  pH < 7.3  Respiratory failure or hypotension  ARF unresponsive to standard therapy  Ethylene glycol level > 50 mg/dL* * May be treated with fomepizole without hemodialysis
  70. 70. Substance Metabolites WGMA High Ketosis CNS Findings Osmol depression GapEthanol Acetaldehyde Alcohol acetic acid + + + + intoxicationEthylene Oxalic acid, Renal failureglycol glycolic acid ++ + - + Hypocalcemia CalciumOxalate crystalluriaIsopropyl Acetone Ketosis withoutalcohol - ++ + ++ acidosis, Hemorrhagic tracheobronchitisMethanol Formaldehyde Blindness, pale formic acid ++ + - + edematous optic disc
  71. 71. Organ Ethylene Glycol Isopropanol Methanol SystemCVS Tachycardia Tachycardia Tachycardia Hypertension Hypotension Hypotension Hypotension Myocardial Dysrhythmias depression MyocarditisCNS Ataxia Areflexia CNS depression Meningoencephalitis Ataxia Convulsions Convulsions CNS depression Dizziness CNS depression Dizziness Headache Inebriation Headache Hypothermia Myoclonus Inebriation Inebriation Muscle weakness Hypothermia
  72. 72. Organ Ethylene Glycol Isopropanol Methanol systemGI Nausea, Vomiting Abdominal pain Abdominal pain Cramping Anorexia Gastritis Gastritis Hematemesis Nausea,vomiting Nausea,vomiting PancreatitisEye Ophthalmologic “Snow field” Nystagmus Blurred vision Hyperemic optic discs Mydriasis Papilledema, blindnessPulmonary Hyperventilation Odor of acetone Tachypnea Respiratory depression Pneumonitis Hemorrhagic Respiratory tracheobronchitis depressionRenal Calcium oxalate Renal tubular acidosis crystalluria Rhabdomyolysis
  73. 73. Thank You

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