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Toxic Alcohols

Toxic Alcohols. Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center. Alcohols: R- OH. OH. H. H. H-C - H. H-C -OH. H-C -OH. H-C - H. H-C -OH. H. H. H. Methanol 1C. Ethanol 2C. Ethylene Glycol 2C. Alcohols: R- OH. H. H. H. H-C - H. H-C -OH. H-C -OH.

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Toxic Alcohols

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  1. Toxic Alcohols Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center

  2. Alcohols: R-OH OH H H H-C-H H-C-OH H-C-OH H-C-H H-C-OH H H H Methanol 1C Ethanol 2C Ethylene Glycol 2C

  3. Alcohols: R-OH H H H H-C-H H-C-OH H-C-OH H-C-OH H-C-OH H-C-H H-C-H H H Benzyl Alcohol Isopropanol 3C Propylene Glycol 3C

  4. Ethanol OH O O H-C-H C-H C-OH ADH ALDH H-C-H H-C-H H-C-H H H H Ethanol Acetaldehyde Acetic Acid ADH = Alcohol Dehydrogenase ALDH = Aldehyde Dehydrogenase

  5. Methanol • Molecular weight 32 • Low freezing point • Highly volatility H H-C-OH H Methanol

  6. Methanol • Gas Line Antifreeze 100% • Windshield washer fluid 30% • Varnish removers • Fuel for food warming 3-70% • Industrial uses

  7. Methanol Metabolism H O O ADH ALDH H-C-OH H-C-H H-C-OH H H H Methanol Formaldehyde Formic Acid ADH: Alcohol Dehydrogenase ALDH: Aldehyde Dehydrogenase

  8. Methanol Toxicity • Delayed onset (8-12hrs) • Anion gap acidosis • Tachypnea • Visual complaints • Retinal metabolism • “Snow storm” Yang CS et al Eye 2005;19:806-809

  9. Methanol Toxicity • CNS depression • Bilateral hemmorhage putamen • Abdominal pain • Multisystem organ failure University of Western Ontario: Neurology Collection

  10. Ethylene Glycol • Molecular Weight 62 • Low Volatility • High boiling point H H-C-OH H-C-OH H Ethylene Glycol

  11. Ethylene Glycol • Coolant/Antifreeze • Solvents • De-Icer

  12. Ethylene Glycol Metabolism H O O H-C-OH C-H C-OH ADH ALDH H-C-OH H-C-OH H-C-OH H H H Ethylene Glycol Glycoaldehyde Glycolic Acid ADH = Alcohol dehydrogenase ALDH = Aldehyde dehydrogenase

  13. Ethylene Glycol Metabolism O O O C-OH C-OH C-OH LDH H-C-OH H-C-H H-C-OH H O O Glyoxylic Acid Glycolic Acid Oxalic Acid B1, Mg2+ B6 -OH- Ketoadipic Acid Glycine + Benzoic Acid Hippuric Acid LDH = Lactate dehydrogenase

  14. Ethylene Glycol Toxicity • Onset 4-6 hours • Anion gap acidosis • Tachypnea pH

  15. Ethylene Glycol Toxicity • Abdominal pain • Hypocalcemia • Calcium oxalate crystals in urine • Renal failure

  16. Identifying Patients for Treatment: Methanol/EG • Serum ethylene glycol or methanol level • Action level for treatment: 25 mg/dL* * Or any level with acidosis

  17. Treatment NG Tube • Limit absorption: • Prevent metabolism or parent compound to toxic metabolite • Enhance elimination • Parent • Metabolites • Correct Derangements ADH Inhibition Substrates/Other Hemodialysis

  18. Limits of Serum Levels • Useful prior to onset of acidosis or in massive overdoses • Parent compound not directly toxic • Levels not universally available EG or Methanol Anion Gap Time

  19. Arterial Blood Gas/Lactate • Acidosis indicates advanced poisoning • Lactate usually low* • Patients with acidosis should receive treatment *Some glycolates are misidentified as lactate

  20. Adjunctive Information:Ethanol • Serum ethanol inhibits metabolism of EG and Methanol • Onset of toxicity EG/Methanol may be delayed

  21. Adjunctive Information: Osmol Gap • Osmol Gap = Measured-Calculated Osmols • Calculated: 2 Na + BUN + Glucose + Alcohol • N = MW Alcohol/10 • Must use freezing point depression 2.8 18 N

  22. Osmol Gap: Limitations • Normal Osmol gap in between – 14 ± 10 • Normal Osmol Gap in setting of poisoning does not rule out a treatable level • Osmol Gap diminishes as parent compound is metabolized Osmol Gap Anion Gap Time

  23. Adjunctive Information • Ethylene glycol: • Limited utility of fluorescence of urine • May note crystals in urine • Methanol • Hyperemia retina or visual complaints

  24. Treatment: Methanol or Ethylene Glycol • Level  25 mg/dL or • Anion gap metabolic acidosis ( non-lactate) with strong suspicion EG or Methanol exposure

  25. Treatment • Ethanol more avid for ADH • 6-8x more avid than ethylene glycol • 4x more avid than methanol Methanol Ethanol Ethylene Glycol ADH ALDH Aldehyde Acid

  26. Ethanol • Concentration = Dose • Vd of ethanol = 0.6 L/kg • Desired concentration 100-200 mg/dL Vd (wt in kg)

  27. Ethanol • Target concentration 100 mg/dL • Proof is 2x concentration • 80 proof is 40% ethanol or 40 grams/100 mL • 0.8 gm/kg loading IV of 10% solution over 1 hour = 8 mL/kg of 10% solution

  28. Ethanol Infusion • 80-130 mg/kg/hour depending on how fast a patient metabolizes • Needs to be increased to 250 mg/kg/hour or higher during dialysis

  29. Ethanol Infusion: Management • Serial ethanol levels • Watch glucose* and sodium* • Observe for respiratory status* * Especially in children

  30. Fomepizole • A blocker of alcohol dehydrogenase • Has replaced ethanol as the agent of choice in known or suspected exposures • Minimal adverse effects

  31. Hemodialysis • Consult nephrology early in acidemic patients • Levels toxic alcohol  25 mg/dL

  32. Adjuncts for Methanol Poisoning • Sodium bicarbonate • pH < 7.30 • Can ion trap formic acid in urine and enhance elimination • Folate administration • Facilitates conversion of one carbon fragments to CO2 • 1mg/kg up to 50 mg every 4 hours

  33. Adjuncts for Ethylene Glycol Poisoning O O O C-OH C-OH C-OH LDH H-C-OH H-C-H H-C-OH H O O Glyoxylic Acid Glycolic Acid Oxalic Acid B1, Mg2+ B6 -OH- Ketoadipic Acid Glycine + Benzoic Acid Hippuric Acid LDH = Lactate dehydrogenase

  34. Adjuncts for Ethylene Glycol Poisoning • To enhance metabolism away from oxalates* • Thiamine 100 mg every 4- 6 hours • Pyridoxine 50 mg every 4-6 hours * Limited data

  35. Diethylene Glycol • Elixir of Sulfanilamide disaster 1937-38 • Renal failure 105 deaths • U.S. Legislation of Drug Safety

  36. Benzyl Alcohol • Preservative in some medications • Gasping Baby Syndrome • Potentially fatal in neonates H H-C-OH Benzyl Alcohol

  37. Isopropanol • Metabolized to acetone • No acidosis • Supportive care H H-C-H H-C-OH H-C-H H Isopropanol 3C

  38. Glycol Ethers • Brake fluid • Solvents • Rarely metabolized to ethylene glycol • Supportive care

  39. Propylene Glycol • Metabolized to lactate • Acidosis in ingestion • IV as diluent QRS widening, hypotension* H H-C-OH H-C-OH H-C-H H Propylene Glycol * Phenytoin diluent

  40. Summary • For Methanol/EG Poisoning • Early Level, ABG, Lactate, Ethanol level • Caution in using osmol gap • Antidote: Ethanol or Fomepizole ( not both) • Hemodiaylsis • Consider sodium bicarbonate/folate for methanol • Thiamine and Pyridoxine for EG

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