One pill can kill


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Pediatric emergency medicine presentation
Emergency Medicine Residency
Thammasat University Hospital

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One pill can kill

  1. 1. Why so common in children?
  2. 2. Background• Developmental milestones – 6-9 months: creep, crawl, and pick up objects – 9-12 months: pick up a pellet and put it in a hand – 15 months: walking, pick up a pellet and put it in a bottle – 18 months: able to consciously dump pellet from bottle (e.g. Tylenol, aspirin, vitamins, adult prescription medications)
  3. 3. Epidemiology• US Poison center reported 2.4 million calls/year• 50% occurred in children ≤6 yrs old• One to three yrs old peak incidence• Less than 50 deaths annually• 99% of ingestions by children under 6 are unintentional.• Approx. 40% of adolescent ingestions reported are intentional.• Approx. 56% of adolescent ingestions are by females
  4. 4. Epidemiology• 10 Fold decrease in deaths since 1950 – Packaging legislation – child resistant closures – Safer medications (tetracyclic > tricyclic) – Consumer Product Safety measures – Poison Centers – Anticipatory Guidance
  5. 5. Most Common Pediatric Exposures
  6. 6. Common deadly ingestion medications• Oral hypoglycemic drugs • Loperamide & Diphenoxylate• Beta-blocker • Salicylates• Calcium channel blocker • Quinine & Quinidine• Alpha-2 adrenergic agonist • Camphor• Cyclic antidepressants • Podophyllin & Colchicine• Opioids • Acetylcholineesterase• Buprenorphine inhibitor
  7. 7. Alpha-2 adrenergic agonist• Resembles Opioids – Bradycardia and hypotension – Decreased LOC, miosis, and respiratory depression/apnea• Clonidine (Catapress), Brimonidine (Alphagan®), Tetrahydrozoline (Visine®), and Oxymetazoline (Iliadin®)• Treatment involves atropine to increase heart rate and intravenous fluid for euvolemic pressure support, may consider vasopressor(Dopamine)• Naloxone may reverse the effects of clonidine on µ-opioid receptors
  8. 8. Oral hypoglycemics• Clinically significant hypoglycemia may occur up to 18-24 hrs• Glipizide, Glyburide, Glimepiride, Glibenclamide, Chlorpropamide• Ingestion in a nondiabetic child requires admission for glucose checks every 1-2 hours• Supportive care/Decontamination – Activated charcoal (ingestion < 1hr or extended release)• Asymptomatic patients allowed to eat
  9. 9. • IV dextrose bolus and infusion for symptomatic patients – 2 mL/kg of 25% dextrose for infant and children IV,IO,NG,PO – 1 mL/kg of 50% dextrose for older children as to adults – insulin release with breakthrough or rebound hypoglycemia• Octreotide can directly inhibit insulin release – Consider for cases refractory to IV dextrose – 4-5 µg/kg/d SC divided Q 6hrs• Consider IM glucagon (0.025-0.1 mg/kg) when unable to PO or IV glucose
  10. 10. Ca-Channel Blocker• Decrease cardiac inotropy, may increase vasodilation• Overdose can block insulin secretion  Hyperglycemia• Long-acting CCBs : should be admitted for 24 hours• Common CCBs include: Amlodipine (Norvasc®), Nicardipine (Cardene®), Verapamil (Isoptin®), and Diltiazem (Herbesser®)
  11. 11. • Treatment with high-dose insulinemia/euglycemia therapy – 1 unit/kg intravenous bolus and 1 unit/kg/hr intravenously with supplemental dextrose as needed (although it rarely is)• Atropine/cardiac pacing• Vasopressors – Norepinephrine/Epinephrine• Calcium gluconate – 0.6 ml/kg IV bolus – 0.6-1.5ml/kg/hr infusion : refractory shock from amlodipine overdose
  12. 12. Beta-Blocker• heart rate but fortunately are unlikely below its intrinsic rate• Blockage of glycogenolysis Hypoglycemia•  in mental status in the more lipid soluble agents that cross BBB – Atenolol is more hydrophilic while Propanolol is most hydrophobic• Symptomatic patients should be given glucagon (0.03-0.05 mg/kg), bypassing beta-receptors to stimulate cAMP cascade, leading to increased intracellular calcium for increased heart rate and contractility.
  13. 13. CCB Vs. BB• Different mechanisms of action, but toxic effects are similar (hypotension and bradycardia)• CNS – BB (lipophylic): sedation, seizure – CCB: alert• Respiratory – BB: bronchospasm• Metabolic – BB: hypoglycemia, mild hyperkalemia – CCB: hyperglycemia
  14. 14. TCA• Block fast Na channels leading to intraventricular conduction delay, widening of the QRS (with subsequent prolongation of QTc), and rightward axis deviation• QRS > 100 msec with a prominent terminal R in aVR is predictive of both ventricular arrhythmia onset and seizure activity• Imipramine, Desipramine, Amitriptylline are regularly prescribed• A child who ingested TCA should be admitted for cardiac monitoring and serial ECGs
  15. 15. Overall effects• Sodium Channel blockage• Potassium channel antagonist• Anticholinergic effect : competitive inhibitor of Ach at Central and Peripheral muscarinic receptor• Antihistaminic effect: Central and Peripheral• Inhibition of Amine reuptake (NE, serotonin)• Inhibition of postsynaptic Central and Peripheral alpha adrenergic receptors• GABA-A receptor antagonist
  16. 16. Cardiotoxicity• Delayed conduction : Na Channel blockade – QRS prolongation – AV block• Arrthymia – Anticholinergic : Sinus tachycardia – Re-entry : Ventricular tachycardia – Prolonged repolarization : Torsade de pointes• Hypotension – Na Channel blockade : Decreased contractility – Alpha adrenergic blockade : Vasodilatation
  17. 17. • Repeated activated charcoal• Serum alkalinization with NaHCO3 to reverse acidic cardiac toxicity – Bolus 1-2 mEq/kg IV and infusion 1-2 mEq/kg/hr – Serum pH 7.45-7.55• Hyperventilation : if NaHCO3 is contraindicated• Seizure : Benzodiazepine, Barbiturate, Propofol But Not Phynetoin• Levophed(NE) is vasopressor of choice if unresponsive to IV, NaHCO3• No Physostigmine !!!• No Flumazenil especially in BZD coingestion!!!
  18. 18. Opioids/Narcotics• Depression in mental status and respiration directly in center• Mostly death due to apnea, hypoxia• A long-acting opioid like OxyContin® peak effects 18-24 hrs• Common narcotics : Oxycodone + Acetaminophen (Percocet®), Oxycodone (OxyContin), Hydrocodone + Acetaminophen (Vicodin®), Fentanyl patches, Methadone, and Hydromorphone (Dilaudid®)• Careful monitoring, supportive care, and administration of naloxone as needed
  19. 19. Buprenorphine• The opioid agonist/antagonist• Active ingredient in Suboxone® (8 mg) and Subutex® (agents used to treat opioid addiction)• Significant respiratory depression in children after only 1 lick• Any pediatric exposure requires a 24-hr hospital admission for respiratory monitoring and administration of naloxone as needed
  20. 20. Loperamide & Diphenoxylate • The synthetic opioids, active ingredients decreasing peristalsis in certain antidiarrheals (Lomotil®, Imodium®, and Tincture of opium) • Too much can cause opioid toxicity • Lomotil® intox. classically “Biphasic reaction” – Initial antimuscarinic symptoms in 2 – 3 hours – Delayed opioid symptoms • Symptomatic patients should receive naloxone and be admitted 24hr for expectant mx
  21. 21. Salicylates• Widely available in OTC products – Most often as Aspirin (acetylsalicylic acid) – Oil of wintergreen (methyl salicylate) – Pepto-bismol (bismuth subsalicylate)
  22. 22. Salicylates• Minimal toxic ingested dose in children: 150 mg/kg• 1 tsp of 98% methyl salicylate contains 7000 mg of salicylate = 90 Baby ASA = > 4 times potentially toxic dose for 10-kg child• Infants : may show just dehydration, rapid breathing• Older kids : GI symptoms (Nausea, Vomiting), CNS depression• Metabolic derangement that induces cerebral and lung edema, seizures, and death
  23. 23. • Uncouple oxidative phosphorylation – Electron transport occurs without ATP synthesis – Increased heat production  Hyperthermia increased energy demand  Glycogenolysis, Lipolysis  Ketones, Hyperglycemia – Impaired gluconeogenesis  Hypoglycemia• Inhibits dehydrogenase enzymes in Krebs cycle  Anaerobic metabolism  Lactate and Pyruvate accumulation
  24. 24. • Initial respiratory alkalosis – Direct stimulation of medulla – Rarely seen in infants or young children• Metabolic acidosis – Accumulation of organic acids from anaerobic metabolism – Acidemia (pH<7.4) implies a severe toxicity with high morbidity• Children can progress to metabolic acidosis w/o an alkalotic phase
  25. 25. • Initial treatment can start with the activated charcoal (1 g/kg PO)• Fluid resuscitation• Levels 20 mg/dL require urine alkalinization with NaHCO3 1-2 meq/kg/hr mixed in D5W or D5½NS depending on age to enhance renal elimination• Prevent acidemia : Avoid sedation, Hyperventilation if intubated• Extracorporeal Removal (Hemoperfusion, Hemodialysis, Exchange transfusion) – Require hemodialysis for acute critical levels (above or approaching 60 mg/dL), patients with ARF, Severe salicylism (Pulmonary edema, altered mental status)
  26. 26. Quinine & Quinidine• Na-channel blockade, leading to QRS widening and arrhythmias• Hypokalemia-related QTc prolongation and Torsades de pointes• Mild cinchonism : Blurred vision, Hearing impairment, and Flushing• Severe : Deafness, Blindness, and Cardiac arrhythmias• Quinines derivatives : Chloroquine & Hydrochloroquine similar toxic• Treatment includes NaHCO3 when QRS is widened, replenishment of electrolytes, and supportive cares• Chloroquine toxicity is treated with diazepam 2 mg/kg
  27. 27. Camphor• Initially nausea and vomiting and can quickly progress to delirium, hallucinations, seizures, and cerebral edema• It is used for its anti-itch, moth repellant, cough suppressant, and muscle-soothing properties in products : Tiger Balm®, Modern (nonnaphthalene) mothballs, Vicks® VapoRub®, and Mentholatum® Ointment• Cause of death : Respiratory depression, Status epilepticus• Treat seizures with benzodiazepines and institute supportive care
  28. 28. Podophyllin & Colchicine• Nausea, vomiting, and diarrhea but can progress to hypotension, tachycardia, metabolic acidosis, and coma mimicking septic shock• Pancytopenia often nadirs 4-7 days after exposure• Dermal overdose can delay presentation up to 24 hrs• Ingestions of greater than 0.5 mg/kg can cause marrow aplasia; as little as 7 mg total has been reported to cause death in adult• Overdose of either agent should be treated with aggressive supportive measures
  29. 29. Acetylcholinesterase inhibitors• Oral AchEIs lead to cholinergic poisoning• Nicotinic effects of hypotonia, miosis, and "floppiness"• Often absent Muscarinic signs : DUMBBELSS• Organophosphate : Insecticides and warfare nerve agents (sarin and VX) are an unlikely exposure risk for toddlers• Oral AchEIs Rivastigmine, Donepezil, Tacrine, and Galantamine used for treatment of Alzheimer dementia are commonly found• Treat muscarinic effects, if present, with atropine• Treat nicotinic effects with pralidoxime
  30. 30. DUMBBELSS
  31. 31. References• Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: nine common agents that kill at low doses. Emerg Med Clin North Am. 2004 Nov;22(4):1019-50.• Matteucci MJ. One pill can kill: assessing the potential for fatal poisonings in children. Pediatr Ann. 2005 Dec; 34(12):964-8.
  32. 32. Thank you!