Managing Toxic Exposure to Acids, Alkalis, Hydrocarbons, Methanol & Ethylene Glycol

1. Specific Toxins Part I

2. Acids • Examples • Toilet bowl cleaner • Rust remover • Phenol (carbolic acid) • Hydrochloric acid • Severe burning of stomach • Absorption, systemic acidemia

3. Acids • Loss of airway = most immediate threat • Secure airway against edema • IV with LR, NS for volume loss • Emesis, gastric lavage contraindicated • Dilution with water, milk NOT recommended

4. Alkalis • Examples • Drain cleaner • Washing soda • Ammonia • Lye (sodium hydroxide) • Bleach (sodium hypochlorite) • Severe burning of esophagus, stricture formation

5. Alkalis • Loss of airway = most immediate threat • Secure airway against edema • IV with LR, NS for volume loss • Emesis, gastric lavage contraindicated • Dilution with water, milk NOT recommended

6. Hydrocarbons • Examples • Kerosene • Gasoline • Lighter fluid • Turpentine • Furniture polish

7. Hydrocarbons • Signs/Symptoms • Choking, coughing, gagging • Vomiting, diarrhea, severe abdominal pain • Chemical pneumonitis, pulmonary edema If the patient is coughing, aspiration has occurred

8. Hydrocarbons • Signs/Symptoms • Euphoria, confusion/anxiety, seizures • Increased myocardial irritability, arrhythmias (adrenergic agents may cause V-fib) • Liver damage, hypoglycemia

9. Hydrocarbons • Management • 100% oxygen with good humidification • IV tko • Monitor ECG • Drug therapy • D50W for hypoglycemia • Diazepam for seizures • Antiarrhythmics

10. Hydrocarbons • Inducing emesis controversial • Should NOT be induced with low viscosity hydrocarbons

11. Hydrocarbons • If ingestion has occurred recently, emesis probably should be induced with: • Halogenated hydrocarbons (carbon tetrachloride) • Aromatic hydrocarbons (toluene, xylene, benzene) • >1cc/kg gasoline, kerosene, naptha • Petroleum products with toxic additives (lead tetraethyl, pesticides)

12. Hydrocarbons Seek advice of medical control and poison control center

13. Methanol methyl alcohol wood alcohol wood naphtha

14. Methanol • Sources • Industry • Household solvents • Paint remover • Fuel, gasoline additives • Canned heat • Windshield washer antifreeze

15. Methanol • Toxic dose • Fatal oral: 30-240ml • Minimum: 100 mg/kg • Example • Windshield washer fluid 10% Methanol • 10 kg child needs only 10 cc to be toxic

16. Methanol • Mechanism of toxicity • Methanol slowly metabolized to formaldehyde • Formaldheyde rapidly metabolized to formic acid • Acidosis • Ocular toxicity

17. Methanol H H C Formaldehyde H O H O H Aldehyde dehydrogenase H O C Formic Acid H O O C H H C _ O H + Methanol Metabolism Alcohol dehydrogenase

18. Methanol • Overdose Presentation • Inebriation • Gastritis • Osmolar gap (osmolar gap as little as 10mOsm/L is consistent with methanol poisoning)

19. Methanol • Overdose Presentation • Latent period of up to 30 hours • Severe anion gap metabolic acidosis • Visual disturbances, blindness (“standing in a snowstorm”) • Seizures • Coma • DEATH

20. Methanol • Management • High concentration oxygen • IV tko • ECG monitor • if < 30 minutes lavage or induce emesis (if not done then it is probably useless)

21. Methanol • Management • Sodium Bicarbonate • Folic acid • 50mg IV every 4 hours • Helps convert formic acid to CO2, H2O • Give specific antidote

22. Methanol • The specific antidote for methanol toxicity ETHANOL 10% EtOH solution in D5W 7.5 ml/kg loading dose and 1.5 ml/kg/hr maintenance 100 proof (50%) EtOH 1.5 ml/kg loading dose and 0.3 ml/kg/hr maintenance

23. H H H H H H H C C C C H H H H O O H H O C H O C Ethanol Metabolism Ethanol Alcohol dehydrogenase Acetaldehyde Aldehyde dehydrogenase Acetic Acid Krebs Cycle

24. Methanol X Ethanol Methanol Alcohol dehydrogenase Acetic Acid Urine CO2 + H2O + Energy

25. Methanol • Specific antidote • Fomepizole (4-methylpyrazole) • Inhibits alcohol dehydrogenase • Produces same end result as ethanol without causing intoxication

26. Ethylene Glycol • Antifreeze (95% ethylene glycol) • Tastes sweet • Kids, animals like taste/drink large quantities

27. Ethylene Glycol • Mechanism of toxicity • Metabolized via alcohol dehydrogenase to glycoaldehyde then to glycolic , glyoxylic, and oxalic acids • Acids lead to anion gap metabolic acidosis • Oxalate binds with calcium • Forms crystals causing tissue injury • Produces hypocalcemia

28. Ethylene Glycol • Toxic dose • Approximate lethal oral dose: 1.5ml/kg • Example • 10 kg child needs 15ml for lethal dose

29. Ethylene Glycol • Overdose Presentation (first 3-4 hours) • Patient may appear intoxicated • Gastritis, vomiting • Increase in osmolar gap • No initial acidosis

30. Ethylene Glycol • Overdose Presentation (after 4-12 hours) • Anion gap acidosis • Hyperventilation • Seizures, coma • Cardiac conduction disturbances, arrhythmias • Renal failure • Pulmonary, cerebral edema

31. Ethylene Glycol • Management • Lavage if within 2 hours • Sodium bicarbonate • Fomepizole or ethanol • Folic acid, pyridoxine, thiamine (enhance metabolism of glyoxylic acid to nontoxic metabolites)

32. Cyanide

33. But first… • A little review of biochemistry and biophysics

34. Staying alive requires energy... • The natural tendency of the universe is for things to become more disorderly. • This trend toward disorder is called entropy. • Complex systems (including us) don’t tend to last long, unless… • They have a constant supply of energy to combat entropy.

35. Organisms capture and store the energy they need in the form of... Adenosine Triphosphate (ATP) • The “currency” cells use to pay off the energy debt built up fighting entropy. • Formed by capturing energy released as the cell breaks down large molecules through glycolysis and the Krebs Cycle.

36. Glycolysis • In cytoplasm • Does not require oxygen • Breaks glucose molecule into two pyruvic acid molecules • Net gain of 2 ATP • If oxygen absent, pyruvate converted to lactate • If oxygen present, pyruvate changed to acetate (acetyl-CoA) and sent to Krebs Cycle

37. The Krebs Cycle • In mitochondria • Requires oxygen • Strips H+ and electrons off of acetate, leaving CO2 • Sends the H+ and electrons to the electron transport chain

38. Electron Transport/Oxidative Phosphorylation • In mitochondria • Electrons pass down a series of carriers--losing energy as they go • It’s like a series of waterfalls • Energy is released and stored as ATP • Electrons and H+ bind to O2, making H2O • 36 ATP produces per glucose molecule

39. NAD NADH2 FAD FADH2 Ox. Cyt. c Red. Cyt. c Ox. Cyt. a Red. Cyt. a Ox. Cyt. a3 Red. Cyt. a3 Oxidative Phosphorylation 2H ADP + Pi ATP Ox. Cyt. b Red. Cyt. b ADP + Pi ATP ADP + Pi ATP 2H+ H2O 1/2O2

40. Putting It All Together • Cells have to have energy to stay alive. • Cells get energy by breaking down glucose in two phases: glycolysis and the Krebs Cycle. • Glycolysis yields 2 ATP and pyruvate. • Pyruvate is changed to acetate (acetyl-CoA) and sent to the Krebs Cycle. • The Krebs Cycle strips hydrogen and electrons off acetate and feeds them into the electron transport chain. • Movement of electrons down the transport chain releases energy which is trapped as ATP. • At the end of the chain, the electrons combine with hydrogen and oxygen to form water.

41. Cyanide • Chemical, plastic industries • Metallurgy, jewelry making • Blast furnace gases • Fumigants, pesticides • Present in various plants • apples, pears, apricots, peaches, bitter almonds

42. Cyanide • Acrylonitrile is metabolized to cyanide • Nitroprusside (Nipride) if given too long is metabolized to cyanide • Acetonitrile in some fingernail glues has caused pediatric deaths Cyanide is so common that all mammals have an enzyme called rhodonase that detoxifies cyanide by converting it to thiocyanate

43. Cyanide • Mechanism of Toxicity • Chemical asphyxiant • Inhibits functioning of cytochrome a3 • Stops electron transport, oxidative phosphorylation • Blocks aerobic utilization of oxygen

44. 1/2 O2 2e- 2e- 2H+ Cytochrome A3 Cytochrome a Fe3+ Fe2+ H2O

45. 1/2 O2 2e- 2e- 2H+ Cyanide Toxicity Cytochrome a X CN- Fe3+ Fe2+ H2O

46. Cyanide • Clinical Presentation • Variable onset speed with different forms • Headache, nausea, dyspnea, confusion • Rapid, weak pulse • Bright-red venous blood • Syncope, seizures, coma • Agonal respirations, bradycardia, cardiovascular collapse

47. Cyanide • Management • Treat all cases as potentially lethal • Support oxygenation, ventilation • ECG • IV tko • Cyanide Antidote Kit

48. Cyanide Antidote Kit • Amyl nitrite, Sodium nitrite • Oxidize iron in hemoglobin from Fe2+ to Fe3+ (methemoglobinemia) • Methemoglobin binds cyanide, removing it from cells • Sodium thiosulfate • Provides rhodonase with sulfide anion • Speeds conversion of cyanide to thiocyanate

49. NO2 - 1/2 O2 2e- 2e- 2H+ Cyanide Antidote Kit Cytochrome a Fe2+ Fe3+ CN- SCN- Fe3+ Fe2+ CN- H2O

50. Cyanide Antidote Kit • Amyl nitrite, sodium nitrite • Only be used in serious cyanide poisonings • Can induce life-threatening tissue hypoxia secondary to methemoglobinemia • Sodium thiosulfate • Can be used by itself • Is relatively benign