1. COMMON INTOXICATIONS IN KIDS Blake Bulloch, MD

2. OBJECTIVES Review new recommendations for GI decontamination Review the common types of intoxications seen in children with recommendations on non-dialytic detoxifying therapies

3. GI DECONTAMINATION Ipecac Gastric Lavage Activated charcoal Cathartics Whole-Bowel irrigation

4. IPECAC 21% to 38% of drug is removed from the stomach if given in first hour Average child presents 1.5 hours post- ingestion, 3.5 hours for adults No evidence that ipecac improves outcome Use in the ED should be abandoned

5. GASTRIC LAVAGE 32% of drug removed if performed  1 hour In ED studies no difference in outcomes versus charcoal alone Complication rate of 3% and includes: –aspiration pneumonia –dysrhythmias –hypoxia and hypercapnia / laryngospasm

6. ACTIVATED CHARCOAL Mean  in drug absorption is 89% if given within 30 min and 37% if given at 1 hour Complications minimal Insufficient data to support or exclude its use after 1 hour post-ingestion

7. CATHARTICS Two reasons cited for use of cathartics which are NOT true: –1) Prevent charcoal induced constipation –2) Decrease bioavailability of the ingestant Not recommended for GI decontamination

8. WHOLE-BOWEL IRRIGATION At 1 hour or longer after ingestion WBI decreases bioavailability 70% Long procedure and labor-intensive Limit to poisons not adsorbed by charcoal and to sustained release pharmaceuticals Should not be used routinely in poisonings

9. RCH POISONINGS (1997-2001) 2637 ER visits for poisoning 730 hospital admissions (28%) 53 ICU admissions –2% of all poisonings –7% of all admissions

10. RCH ICU ADMISSIONS

11. TRICYCLIC ANTIDEPRESSANTS

12. PATHOPHYSIOLOGY Most toxic reactions are due to: (1) Anticholinergic effects (2) Excessive blockade of norepinephrine reuptake at the postganglionic synapse (3) Direct quinidine-like effects on the myocardium

13. CLINICAL PRESENTATION Quinidine-like effects depress myocardial conduction – Prolonged QRS, QT or PR intervals –Torsade de pointes Ataxia, hallucinations, coma, seizures Other anticholinergic effects

14. MANAGEMENT Sodium bicarbonate: –Increases the plasma protein binding of TCAs –May help overcome sodium channel blockade If hypotensive may consider norepinephrine infusion (0.1-0.3 ug/kg/min) –Less ventricular arrhythmias than with dopamine?

15. CARDIAC DRUGS Beta-Adrenergic Blockers and Calcium Channel Blockers

16. PRESENTATIONS Bradycardia Hypotension Coma Convulsions Hypoglycemia: Beta-blockers Hyperglycemia: Calcium channel blockers

17. MANAGEMENT Atropine, fluid boluses and pressors to treat bradycardia and hypotension Glucagon 3-5 mg/kg IV bolus up to 10 mg followed by an infusion of 2-5 mg/h CCB: 10% Ca gluconate 0.6 ml/kg or 10% Ca chloride 0.2 ml/kg Pacemaker

18. CARBAMAZEPINE

19. CLINICAL PRESENTATION Coma Respiratory depression Seizures Ventricular arrhythmias Other anticholinergic effects (Ileus, hyperthermia, urinary retention)

20. MANAGEMENT Supportive Seizures: –Benzodiazepines –Phenobarbital –Not phenytoin. Charcoal hemoperfusion and hemodialysis have reduced [serum] by 25-50%

21. METHANOL AND ETHYLENE GLYCOL

22. PATHOPHYSIOLOGY Metabolites cause the poisoning Ethylene glycol  glycoaldehyde  glycolic oxalic acids Methanol  formaldehyde  formic acid These cause metabolic acidosis, blindness, and cardiovascular instability

23. TRADITIONAL TREATMENT Ethanol administration to occupy binding sites on alcohol dehydrogenase and prevent generation of toxic metabolites Hemodialysis to eliminate parent compound Sodium bicarbonate to treat metabolic acidosis

24. FOMEPIZOLE Competitively inhibits alcohol dehydrogenase Loading dose 15 mg/kg followed by 10 mg/kg q12h for 4 doses then 15 mg/kg q12h Doses given intravenously over 30 minutes

25. FOMEPIZOLE VS ETOH Does not require separate preparation Adverse effects: HA, nausea and vertigo vs altered mental status and hypoglycemia Hemodialysis still useful

26. IRON

27. PATHOPHYSIOLOGY Excess iron is directly caustic to the GI mucosa  hypovolemia and shock Free unbound iron: – Increases capillary permeability –Accumulates mainly in the liver and concentrates in mitochondria disrupting oxidative phosphorylation  lactic acidosis

28. CLINICAL STAGES Stage 1: GI phase (within hours) Stage 2: Latent (6 - 24 hours) Stage 3: Shock phase (variable) Stage 4: GI tract scarring (days to weeks)

29. MANAGEMENT WBI unless ileus, obstruction, perforation or GI hemorrhage Deferoxamine mesylate is a chelating agent that removes iron from tissues and free iron from plasma Dose: 15 mg/kg/hour

30. DFO INDICATIONS 1) Symptomatic patients with more than transient minor symptoms 2) Patients with lethargy, abdominal pain, hypovolemia or acidosis 3) Positive AXR 4) Any symptomatic patient with iron level > 300 ug/dl

31. BENZODIAZEPINES

32. PATHOPHYSIOLOGY Benzodiazepines act on the CNS by potentiating gamma-aminobutyric acid which renders the postsynaptic receptor sites to be less excitable

33. CLINICAL PRESENTATION Most commonly; ataxia, lethargy and slurred speech Respiratory depression and coma Hypotension and hypothermia are rare

34. MANAGEMENT Flumazenil –Competitive BDZ receptor antagonist Adult dose is 0.2 mg IV every minute until response achieved (maximum 3 mg) –Literature to support higher doses Pediatric dose recommendation: –10 ug/kg for 2 doses

35. SULFONYLUREAS

36. BACKGROUND Sulfonylureas stimulate insulin secretion which results in hypoglycemia Most common are glyburide, glipizide and chlorpropamide Relatively uncommon poisoning but high morbidity and mortality

37. TRADITIONAL TREATMENT Routine treatments are often ineffective because they stimulate endogenous insulin secretion (dextrose and glucagon) Corticosteroids are unreliable Diazoxide (antihypertensive) is an inhibitor of insulin secretion and is effective Concern exists over possible hypotension

38. OCTREOTIDE Inhibits the secretion of insulin Stabilizes blood glucose levels and prevents rebound hypoglycemia Dose is 50 ug subcutaneously q8-12h Recommendation: Octreotide to all patients who remain hypoglycemic after a 1 g/kg dose of dextrose

39. ACETAMINOPHEN

40. PATHOPHYSIOLOGY Metabolized in 3 ways: –Glucuronidation –Sulfation –Via cytochrome P450 pathway to a toxic intermediate that conjugates with glutathione In OD glutathione becomes depleted

41. MANAGEMENT GI decontamination Obtain 4 hour level N-Acetylcysteine (NAC): –United States: 140 mg/kg P.O. then 70 mg/kg q4h for 17 doses (Total time 72 h) –Everywhere else: I.V. infusion x 3 (Total time: 21 h)