Common Poisonings ( Toxidromes )

1. Common Poisonings (Toxidromes) B. Wayne Blount, MD, MPH

2. Epidemiology • US Poison Centers receive 1.5 million calls a year regarding pediatric ingestions. • 79% of these calls involve children younger than age six. • 56% of pediatric exposures are from products around the house including medicines, cleaning agents, pesticides, plants and cosmetics.

3. Acute Poisoning in the Emergency Department • Common - 3-5% of ED attendances • 2000 Deaths per year Often multiple drugs • DON’T FORGET ALCOHOL !!

4. Epidemiology: “the numbers” • Nearly 90% of exposures occur at home • During pre-adolescence: slight male predominance • This reverses in ages 13-19 with females accounting for 55 % • Children, especially under age 6, are more likely to have unintentional poisonings About half of all poisonings among teens are classified as suicide

5. Epidemiology: “the numbers” • Approximately 1/3 of ingestions of toxic medications occur with meds intended for someone else

6. Definitions • Artery: • The Study of Paintings

7. Objectives • General Principles in the Management of ANY Poisoning • Specific management options with certain substances • Salicylates Ethylene Glycol • Acetominophen Pesticides • Iron Lead • Tricyclics Hydrocarbons

8. General Management -History • Applies to ANY episode of Poisoning • WHAT • HOW MUCH (Ideally mg/Kg) • WHEN • WHAT ELSE (Including Alcohol) • WHY • Use Paramedics, friends, relatives, anyone!!

9. General Management -1 • A (Airway) • B (Breathing) • C (Circulation) • D (Disability-AVPU/ Glasgow Coma Scale) • DEFG ( Don’t Ever Forget the Glucose) • G (Get a set of basic observations)

10. General Management -2 • Use all your senses, search for the clues • LOOK • Track Marks • Pupil Size • Hear • Type Breathing (Kussmaul, Hyperventilation) • FEEL • Temperature, Sweating • SMELL • Alcohol • Fruity • I would NOT taste

11. Specific Management Options-1 • DECREASING DRUG ABSORPTION • Decontaminate • Gastric Lavage ( Unpopular - need to protect the airway, may push drug through pylorus into small bowel.) • Absorbants ( Activated Charcoal , usually within 1 hour of ingestion, longer repeated doses in drugs that delay gastric emptying e.g. Aspirin)

12. Specific Management Options -2 • INCREASING DRUG ELIMINATION • Alkaline Diuresis (Aspirin) • Hemodialysis (Aspirin)

13. Specific Management Options - 3 • ANTAGONISING THE EFFECTS OF THE POISON • Desferrioxamine (IRON) • Naloxone (OPIATES) • N Acetylcysteine (Acetominophen) • Digibind (Digoxin) • Flumazenil (Benzodiazepines)

14. Definitions • Barium • What doctors do when patients die

15. Diagnosis • Physical Exam: • Vital signs and general appearance • Thorough PE • Close attention to neuro exam • Pupils • Reflexes and posture • Mental status • Bowel sounds • Mucous membranes and skin moisture/appearance • Characteristic odors • Nosebleeds, needle tracks, blistering

16. Physical Exam Findings • Sympathomimetic (meth, amphetamines, cocaine, opiate withdrawal, PCP) • Hyperthermia, tachycardia, hypertension, mydriasis, warm/moist skin, agitated • Cholinergic (organophosphates, betel nut, VX, Soman, Sarin) • SLUDGE (Salivation, Lacrimation, Urinary incontinence, Diarrhea/Diaphoresis, GI upset/hyperactive bowel, Emesis) • Anticholinergic (antihistamines, atropine, phenothiazines, TCA) • Hyperthermia, tachycardia, HTN, hot/red/dry skin, mydriasis, unreactive pupils, unrinary retention, absent bowel sounds • Opioids (codeine, dextromethorphan, heroin) • Miosis, respiratory depresssion, mental status depression

17. Diagnostic Considerations • Before proceeding, consider other aspects of the differential diagnosis ( CVA, trauma, meningitis, post-ictal state, behavioral or psych disorders). • Labs to evaluate glucose, acid-base status and electrolytes, BUN/Cr, carboxyhemoglobin, hepatic enzyme levels, urinalysis (UA preg), serum osmolality, serum acetaminophen levels • EKG • Save samples of blood, urine, gastric contents • General qualitative tox screens of little value (except when abuse is suspected), but are rapid and could offer clue to antidote; may have role in the difficult dx or critically ill; Quantitive measurements in certain toxic exposures

18. Diagnostic Considerations • Ocular/dermal: • pH testing may reveal acid or alkali • Hypoxemic while asymptomatic may suggest methemoglobinemia • Cardiac • EKG shows arrhythmia (TCA) • Blood color on filter paper that remains brown after air exposure suggests methemoglobinemia (possibly from benzocaine-containing products, aniline dyes, nitrites) • Signs of hypocalcemia in ethylene glycol, hydrofluric acid • Urine fluorescence in ethylene glycol • Ferric Cl creates purple reaction with salicylates and phenothiazines in urine • Small opacities on x-ray may show halogenated toxins, heavy metals, lithium, densely packed products, phenothiazines, enteric-coated meds

19. Diagnostic Considerations • MUDPILES CAT for high anion gap acidosis • Methanol or metformin • Uremia • DKA • Paraldehyde or phenformin • Iron, INH, Ibuprofen • Lactic acidosis • Ethylene glycol • Salicylates • Cyanide • Alcohol or acids (valproate) • Toluene or Theophylline

20. Diagnostic Considerations • Toxins requiring quantitative levels at a set point: • Acetaminophen • Carbon monoxide • Ethanol, ethylene glycol • Heavy metals (24 hour urine) • Iron • Methanol • Methemoglobin • Toxins requiring quantitative serial levels • Aspirin/salicylates, tegretol, digoxin, phenobarbital, phenytoin, VPA, theophylline

21. Definitions • Dilate • Live longer than your kids

22. Specific Toxidrome Patterns

23. Common Toxidrome Findings

24. Common Toxidrome Findings

25. Approaching the Poisoned Child

26. Salicylates

27. Pharmacology • Irreversibly inhibits the enzyme cyclooxygenase. This inhibits prostaglandin synthesis. • Since prostaglandins are not synthesized, their downstream byproducts are never released such as: IL-6, TNF, and alpha and beta interferons. • Believed to directly inhibit neutrophils to decrease the inflammatory response.

28. Pathophysiology • Salicylates stimulate the brainstem to cause hyperventilation (respiratory alkalosis). • Multifactorial renal impairment leads to accumulation of sulfuric and phosphoric acids. • Interfere with the Krebs Cycle limiting substrates for ATP generation.

29. Pathophysiology Continued • Uncouples oxidative phosphorylation which leads to increased pyruvic and lactic acid level and generates heat. • Causes salicylate induced fatty acid metabolism which produces ketone bodies. This ketoacidosis contributes a significant portion to the overall metabolic acidosis.

30. Salicylate Poisoning • Ingestion of 150 mg/kg of salicylates causes intoxication. • Level of 50-80 mg/dL causes moderate symptoms. • Severe symptoms are associated with blood levels > 80 mg/dL.

31. Clinical Manifestations • Early symptoms are usually non-specific such as nausea and vomiting. • Tinnitus with or without hearing loss can also be an early sign. • Hyperventilation is often a warning sign of a significant ingestion. (respiratory alkalosis) • CNS signs can vary from vertigo to hallucinations to stupor. Coma is rare except in massive overdoses. • In large overdoses, almost every organ system becomes involved.

32. Treatment • Address the A,B, C’s. • Detailed history and exam. • Laboratory evaluation and consider a blood gas if your history suggests an ingestion. • Activated charcoal should be given. Evidence for multidose charcoal is equivocal. • The use of sodium bicarbonate. • Measure serial salicylate levels and chemistries.

33. Sodium Bicarbonate Therapy • The goal is to titrate the urinary pH to 8. BUT • Excretion of hydrogen will make it “nigh on to” impossible to titrate your therapy to a urinary pH of 8. • Potassium must be monitored closely because if the potassium drops, the kidney will retain the potassium and excrete hydrogen.

34. Urine is alkalinized by administering • 1-2 mEq/kg of sodium bicarbonate at half hourly intervals for 4 hours • in alkaline urine, salicylates do not diffuse back into the tubular cells from the lumen. • Potassium salts should be given (3-5 mEq/kg/day) to replace the potassium losses

35. Indications for Hemodialysis • Renal failure. • Congestive heart failure (relative). • Acute lung injury. • Persistent CNS disturbance. • Severe acid-base or electrolyte imbalance, despite appropriate treatment. • Hepatic compromise with coagulopathy. • Salicylate concentration (acute) >100 mg/dL.

36. Definitions • Impotent • Distinguished, Well Known

37. Ethylene Glycol and Methanol fomepizole folate thiamine Mg, B6

38. The Osmolar Gap

39. Treatment • Fomepizole or ethanol – both inhibit alcohol dehydrogenase. • Cofactors • Pyridoxime • Folate • Magnesium • Thiamine

40. Fomepizole Dosing • Loading dose • 15 mg / Kg • Next 4 doses • 10 mg / Kg • Subsequent doses • 15 mg / Kg • Dosing schedule is every 12 hours except during dialysis. Then it is every 4 hours during dialysis as it gets dialyzed off.

41. Definitions • Nitrates • Cheaper than day rates

42. Pesticides • Specifically organophosphates and carbamates. • They work by inhibiting acetylcholinesterase. So… • Present with cholinergic symptoms

43. Organophosphorus (insecticides and pesticides) Poisoning • Organic phosphate insecticides cause irreversible inhibition of the enzyme cholinesterase. As result acetylcholine accumulates in various tissues. Excessive parasympathetic activity occurs. These agents are absorbed by all routes including skin and mucosa.

44. Cholinergic Symptoms

45. Symptoms manifest quickly usually within a few hours • Include weakness, blurred vision, headache, giddiness, nausea, and pain in chest. • Sweat profusely. papilledema may occur. • Reflexes absent and sphincter control lost.

46. Nicotinic Symptoms • Think the days of the week ! • M ydriasis • T achypnea • W eakness • T achycardia • F asiculations • W eekend: “Wee” ones : Pediatric patients tend to present with a predominance of nicotinic symptoms!!!

47. Weakness from Pesticides

48. Treatment • If the insecticide was in contact with skin or eyes, Wash thoroughly . • Atropine 0.02 mg / Kg IV. Repeat as needed and titrate to respiratory secretions. It will likely take massive doses!! • Pralidoxime (2-Pam) 20-40 mg / Kg bolus followed by 10-20 mg / Kg /hour infusion. • Remember to send RBC and Plasma Cholinesterase levels upon arrival and daily.

49. Definitions • Rectum • Damn near killed him

50. Acetaminophen Toxicity