Pediatric Poisonings

1. Pediatric Poisonings Mark Sutter, MD

2. Overview • Epidemiology • Important Legislation • Packaging and Marketing Problems • Physiologic Differences • Iron • Pesticides • Deadly Pediatric Poisons

3. 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.

4. Epidemiology • 99% of ingestions by children under 6 are unintentional. • Approximately 40% of ingestions reported to the poison center by adolescents are intentional. • Approximately 56% of adolescent ingestions are by females.

5. Epidemiology

6. Legislation • The Poison Prevention Packaging Act of 1970. (PPPA) • Requires child protective packaging of hazardous household products. • Over the last 30 years the list of substances regulated by the PPPA have expanded to include medicines, solvents, and oils. • Data shows reduction of 45% mortality of pediatric patients since the introduction and expansion of PPPA.

7. Special Pediatric Issues • ALL THINGS TEND TO END UP IN THE MOUTHS OF YOUNG CHILDREN!!

8. Which is Candy?

9. Sweet Tarts vs. Ecstacy

10. Poison Center Campaign

11. Physiologic Differences • Blood brain barrier still more permeable to toxicologic substances until around 4 months. • No studies demonstrating increased permeability, rather this is an estimate based on toxicity noted with smaller doses than expected. • Higher metabolic demands. • Decreased ability to glucuronidate in the infant period. Second trimester pregnancies that were terminated showed only 10% activity of the P-450 system. • No better studies to date, but most believe between ages 2-4 years that glucuronidation is equivalent to adults. • Decreased glycogen stores.

12. Physiologic Differences • Increased body surface area can lead to thermoregulatory issues. • Children reside lower to the ground. This puts them at higher risk for ingesting compounds heavier than air. Often adults will NOT have the same exposure. • Inability to avoid hazards – they do not read warning labels or “Do Not Enter” signs.

13. Iron • The most common cause of death in toddlers. • Classically taught as having five clinical stages. • Remember prenatal vitamins, supplements, and “natural products”.

14. Iron • Toxic doses occur at 10-20mg/Kg of elemental iron. • Prenatal vitamins typically contain about 65 mg of elemental iron. • Childrens vitamins contain about 10-18 mg of elemental iron.

15. The Five Stages • Stage 1 • Nausea, vomitting, abdominal pain and diarrhea. • Stage 2 • This is the latent phase often between 6-24 hours as the patient resolves GI symptoms. • Stage 3 • Shock stage involving multiple organs including coagulopathy, poor cardiac output, hypovolemia, lethargy and seizures. • Stage 4 • Continuing of hepatic failure and ongoing oxidative damage by the iron in the reticuloendothelial system. • Stage 5 • Gastric outlet obstruction secondary to scarring and strictures.

16. Management • Detailed history and physical including a rectal exam for frank blood. • Aggressive fluid resuscitation and intravenous access. • Whole bowel irrigation and KUB to look for pills. • Laboratory analysis for CBC, chemistry, and iron levels (peak around 4 hours). • Will often require repeat levels with a repeat chemistry. • TIBC has no utility in the acute overdose setting.

17. Management

18. Management • If the patient is in shock, remember to atleast type and screen (if not cross match) for blood. • Give deferoxamine before iron level is back if the patient is in shock. • Deferoxamine was derived from streptomyces pilosus. • Hypotension and allergic reactions are seen. • ARDS is a known complication and usually limit its use to 24 hours or less.

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

20. Cholinergic Symptoms

21. Nicotinic Symptoms • Remember the days of the week ! • Mydriasis • Tachypnea • Weakness • Tachycardia • Fasiculations • Pediatric patients tend to present with a predominance of nicotinic symptoms!!!

22. Weakness from Pesticides

23. Treatment • 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.

24. The Expanded “One Pill Kill”

25. Calcium Channel Blockers Cyclic Antidepressants Lomotil Opiates / Opiods Salicylates (methyl) Toxic Alcohols Sulfonylureas Camphor Clonidine and imidazolines Antimalarials The Deadly Pediatric Poisons

26. Calcium Channel Blockers • Three major classes • Phenylalkylamine • Benzothiazepine • Dihydropyridine • Block L-type channels • Cause hypotension, bradycardia, and arrythmias. • Immediate and sustained release. • Usually not the childs medication.

27. Calcium Channel Blockers • Manage A, B, C’s • Check Labs and EKG • Fluids • Calcium • Glucagon • Pressors • High Dose Insulin • Atorpine and Pacing

28. Calcium Channel Blockers • May be able to wean pressors with insulin. • Insulin dosage is 1 unit / kg bolus and 0.5 units / kg / hour drip. • Monitor sugar Q20 minutes for the first few hours. • Most will NOT become hypoglycemic.

29. Cyclic Antidepressants • They were the leading cause of poisoning fatality until 1993. • They interfere with reuptake of biogenic amines and serotonin at the nerve terminal. • Manifest toxicity by anticholinergic effects, alpha-1 inhibition, sodium channel blockade, and can inhibit GABA. • Cause CNS and cardiovascular toxicity with arrythmias leading to mortality.

30. EKG Findings

31. EKG Findings

32. Cyclic Antidepressant Managment • Manage A, B, C’s aggressively • Optimize electrolytes • Follow serial EKG’s and use Bicarb if: • QRS >100 or 110 msec • aVr > 3 mm • If bicarbonate and magnesium are not effective, lidocaine is the antidysrhythmic of choice. • Norepinephrine is the pressor of choice for refractory hypotension.

33. Is it the Sodium or the Bicarb? • The answer is BOTH! • Sodium overcomes the partial blockade from cyclic antidepressants. • Alkalinization does change binding properties.

34. How does the bicarb work? • Initially thought to increase protein binding thus limiting free drug in the blood • Rat study using alpha-1 acid glycoprotein (AAG) only decreased arrhythmias at massive doses. AAG is a proven TCA binder. • Current theories is that the ionic form of the TCA binds to the sodium channel causing blockade and the bicarbonate changes the TCA from the ionic form to the neutral form causing less blockade.

35. Lomotil • Antidiarrheal agent containing both diphenoxylate and atropine. • Both agents are absorbed by the GI tract and absorption may be delayed in overdose due to inhibitory effects on smooth muscle motility. • Diphenoxylate is an opoid that is metabolized to difenoxin which is 5 times more potent than the parent compound and has half life of 12-14 hours.

36. Lomotil • Patients manifest signs and symptoms of opiate toxicity. • Respond well to naloxone and supportive care. • Current recommendations are for a minimum of 24 hour observation.

37. Opiates / Opiods • Typically present with respiratory depression, altered mental status, and miosis. • Address the patient like any other “altered mental status” • Key point is to remember to consider an opiate ingestion.

38. Naloxone Dosing • Usually start with 0.01-0.1 mg / Kg. • Repeat as frequently as needed to reverse symptoms. • If a drip is required, calculate how much naloxone was used in the first hour and start the drip at 2/3 that dose.

39. Salicylates

40. 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.

41. Salicylate Metabolism

42. 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.

43. 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.

44. 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. • 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.

45. 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.

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

47. 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.

48. Toxic Alcohols • Ethylene Glycol • Antifreeze • Coolant Mixtures • Methanol • Windshield wiper fluid • Moonshine

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

50. The Osmolar Gap