1. Poisoning/Overdose General Management Poisoning is Exposure to substance that is toxic in any amount

2. Overdose Exposure to substance in excess amount resulting in toxic effects

3. 1998 TESS* Data 2,241,082 reported human exposures 97.9 % at home Peak volume 4pm-10pm 91% of calls 8pm-midnight * The Toxic Exposure Surveillance System (US based)

4. Exposures by Age < 6 years old 52.7% < 3 years old 39.6% 775 fatalities 0.03% of total exposures ages 20 - 49 years = 56% >6 years = 2.1% Fatalities

5. Number of Substances 92.8% of all cases--one substance 44.7% of fatal cases-->2 substances

6. Management Location Managed on site 75.2% Treated, released at ER only 12.3% Admitted to critical care 2.7% Refused referral * 2.0%

7. Therapy No therapy 11.9% Observation only 12.7% Decontamination only 59.6% Activated charcoal 6.8% Ipecac 1.2%

8. Most Common Substances Cleaning substances 10.2% Analgesics 9.6% Cosmetics 9.4% Plants 5.5% Foreign bodies 4.6% Cough, cold 4.5% Bites, stings 4.1% Insecticides, pesticides, rodenticides 3.9% Sedative, hypnotics, antipsychotics 3.2% Antidepressants 3.0% Hydrocarbons3.0% Alcohols2.5%

9. Largest Number of Deaths Analgesics264 Antidepressants152 Stimulants, street drugs118 Cardiovascular medication118 Sedatives, hypnotics 89 Alcohols 56

10. Indicators Sudden onset of CNS signs: –Seizures –Coma –Decreased LOC –Bizarre behavior Sudden onset of: –Abdominal pain –Nausea –Vomiting

11. Indicators cont Sudden onset of unexplained illness Bizarre, incomplete, evasive history Trauma (>50% of adult trauma EtOH, drug-related) Pediatric patient with arrhythmias

12. History What? How much? How long? Multiple substances? Treatment attempted? How? Whose advice? Psychiatric history? History of suicide?

13. Scene Survey Check out scene for : –1 –2 –3 –4 Where do you look for clues?

14. General Management Support ABC’s –Secure airway, secure with advanced airway if needed –Ensure adequate oxygenation, ventilation –Maintain adequate circulation Monitor ECG Obtain vascular access Manage hypotension initially with volume Use vasopressors cautiously

15. General Management Keep patient calm Maintain normal body temperature Evaluate nature/toxicity of poison –Check container, package insert, poison center information –Treat the patient, not the poison

16. General Management Rule out (differential diagnosis) –Trauma –Neurological disease –Metabolic disease Base general management on route of poison entry

17. Poison Entry Ingestion Slow movement from injection site throughout body Remove from skin surface Remove from exposure; Support oxygenation, ventilation Prevent absorption from GI tract Inhalation Absorption Injection

18. Ingested Poisons Objective Remove from GI tract before absorption occurs

19. Ipecac RARELY used anymore If used, has to have been initiated within few minutes after ingestion Vomiting in 20-30 minutes Only removes about 32% of contaminate Many contraindications

20. Ipecac Dose –15 cc if 12 months to 12 years old –30 cc if >12 years old Follow with 2-3 glasses of water Keep patient ambulatory if possible

21. Ipecac If no vomiting after 20 minutes, repeat When emesis occurs, keep head down Collect, save vomitus for analysis

22. Ipecac Contraindications –Comatose or no gag reflex –Seizing or has seized –Caustic (acid or alkali) ingestion –Low viscosity hydrocarbon ingestion –Late term pregnancy

23. Ipecac Contraindications –Severe hypertension, cardiovascular insufficiency, possible AMI –Ingestion of: Strychnine Phenothiazines (Thorazine, Stellazine, Compazine) Tricyclic antidepressants Iodides Silver Nitrate

24. Lavage Commonly used in ED’s Removes about 31% of substance Helps get activated charcoal in patient, especially if patient is unconscious Not helpful for sustained release tablets Will not remove large tablets

25. Activated Charcoal Adsorbs compounds, prevents movement from GI tract Very effective at adsorbing substances Binds about 62% of toxin Dose –5 - 10X estimated weight of ingested chemical

26. Activated Charcoal Inactivates Ipecac Do not give until vomiting stops Do not give with –Cyanide –Methanol –Tylenol (+) Containers must be kept airtight Can be given PO via slurry or by NG

27. Inhaled Poisons Objective: Move to fresh air; optimize ventilation and protect personnel from exposure

28. Absorbed Poisons Objective: Remove poison from skin Liquid: Wash with copious amounts of water Powder: Brush off as much as possible, then wash with copious amounts of water Protect personnel from exposure

29. Dilute / Irrigate / Wash Use soap, shampoo for hydrocarbons No need for chemical neutralization - heat produced by reaction could be harmful

30. Eye Irrigation Wash for 15 minutes Use only water or balanced salt solutions Remove contact lenses Wash from medial to lateral

31. Examples of Specific Toxins

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

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

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

35. 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

36. Hydrocarbons Examples –Kerosene –Gasoline –Lighter fluid –Turpentine –Furniture polish

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

38. Methanol methyl alcohol wood alcohol wood naphtha

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

40. 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

41. Methanol Mechanism of toxicity –Methanol slowly metabolized to formaldehyde –Formaldheyde rapidly metabolized to formic acid Acidosis Ocular toxicity

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

43. Cyanide

44. But first… A little review of biochemistry and biophysics

45. 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.

46. Organisms capture and store the energy they need in the form of... 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. Adenosine Triphosphate (ATP)

47. 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. CN messes with this !

48. Cyanide Chemical, plastic industries Metallurgy, jewelry making Blast furnace gases Fumigants, pesticides Present in various plants –apples, pears, apricots, peaches, bitter almonds Remember there is CN gas released by BURNT plastics (e.g fire!!)

49. 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

50. Salicylates

51. Examples –Aspirin –Oil of wintergreen Uses –Analgesics –Antipyretics –Anti-inflammatories –Platelet function inhibitors

52. Salicylates Mechanism of Toxicity –Direct stimulation of respiratory center, causing respiratory alkalosis –Irritation of gastrointestinal tract, causing decreased motility, pylorospasm, nausea, vomiting, hemorrhagic gastritis –Decreased prothrombin levels/platelet dysfunction, causing prolonged clotting times –Uncoupling of oxidative phosphorylation

53. Results of Oxidative Phosphorylation Uncoupling ATP production decreases, resulting in CNS and cardiovascular failure. Cells attempt to compensate by increasing the rate they process glucose anaerobically through glycolysis. Lactic and pyruvic acids accumulate, leading to metabolic acidosis. Hypoglycemia results as liver sugar stores are depleted. In absence of sugar cells begin to metabolize lipids, ketone bodies are produced, acidosis worsens. Energy normally trapped as ATP is wasted as heat, causing a rise in body temperature. The rise in body temperature accelerates metabolism, increasing tissue oxygen demand and worsening acidosis.

54. Salicylates –Vomiting –Lethargy –Hyperpnea –Respiratory alkalosis –Metabolic acidosis –Coma –Seizures –Hypoglycemia –Hyperthermia –Pulmonary edema Clinical Presentation: Acute Toxicity

55. Salicylates Clinical Presentation: Chronic Toxicity –Usually young children, confused elderly –Confusion, dehydration, metabolic acidosis –Higher morbidity, mortality than acute overdose –Cerebral, pulmonary edema more common

56. Salicylates Acute Toxicity Management –Oxygen, monitor, IV –GI tract decontamination –Activated charcoal –Replace fluid losses, but do NOT overload –Control hyperthermia

57. Salicylates Acute Toxicity Management –Bicarbonate for metabolic acidosis –D50W for hypoglycemia –Diazepam for seizures

58. Acetaminophen

59. Acetamophen Examples –Tylenol –Tempra –Many drugs contain this also Uses –Analgesic –Antipyretic

60. Acetaminophen Mechanism of toxicity –N-acetyl p-benzoquinonimine, normal product of acetaminophen metabolism, is hepatotoxic –Normally is detoxified by glutathione in liver –In overdose, toxic metabolite exceeds glutathione capacity, causes liver damage

61. Acetaminophen Management –Induce emesis –Do NOT give activated charcoal in general –Give specific acetaminophen antidote

62. Acetaminophen The specific antidote for acetaminophen toxicity.

63. Mucomyst N-acetylcysteine l Another sulfur-containing amino acid l Substitutes for glutathione. l Allows continued detoxification of NAPBQI. l 140mg/kg initially followed by 70mg/kg every 4 hours 17 times. l Tastes, smells like rotten eggs l Mix with chilled fruit juice to decrease odor, taste

64. More to come Review –Cocaine OD –TCA OD –Opoid OD –MDMA - E –GHB