Highlights in Pediatrics Toxicology

1. Highlights in Pediatrics Toxicology Dr. Manal Al Maskati Oct, 2011 - Kuwait

2. Objectives Few words about poisoning in Pediatrics. Key points in poisoning history and physical examination. Some important Toxidromes. Common cases of poisoning in Pediatric age group.

3. Introduction Poisonings too common in pediatric world. Around 6,000,000 children ingest potentially toxic substance each year nationwide. Most frequently in children ages 1-5 years old. Most common exposures are substances found around the house (makeup, household chemicals, over the counter medicines, and houseplants). Substances either nontoxic or, if toxic, in insufficient amounts to cause significant problems. Second peak of exposures in adolescent population, most are suicide attempts.

5. History Three key questions in all poisoning cases:  1) WHAT substance(s) was ingested?  2) WHEN did the ingestion occur?  3) HOW MUCH was ingested?

6. History Answers to questions will provide valuable information about: a) Severity of the ingestion. b) Potential benefits/efficacy of GI decontamination. c) Whether or not therapeutic interventions necessary. d) Accurate interpretation of specific drug levels. e) Disposition of the patient.

7. Toxicologic physical examination a) Eyes: pupillary size, symmetry and response to light presence of nystagmus (vertical or horizontal). b) Oropharynx: moist or dry mucus membranes, presence/absence of the gag reflex, presence of any particular or distinctive odors. c) Abdomen: presence/absence and quality of bowel sounds. d) Skin: warm/dry, warm/sweaty or cool. e) Neurologic: level of consciousness and mental status, presence of tremors, seizures or other movement disorders, presence/absence and quality of deep tendon reflexes.

8. Toxidromes Refer to specific constellation of signs and symptoms specific class or type of toxic substance. 1. Anticholinergics (atropine, antihistamines, cyclic antidepressants): Tachycardia, hypertension, tachypnea (red as a beet). Mydriasis (blind as a bat). Agitation, hallucinations/delirium, seizures, hypoactive bowel sounds( mad as a hatter). Warm/dry skin, dry mouth (hot as a hare ,dry as a bone).

9. Toxidromes 2. Sympathomimetics (cocaine, amphetamines, PCP, decongestants, beta-agonists, theophylline): Tachycardia, hypertension, tachypnea. Mydriasis. Agitation, hallucinations, delirium, seizures, hypoactive bowel sounds. Warm/sweaty skin.

10. Toxidromes 3.Cholinergics (organophosphate and carbamate insecticides): "D-U-M-B3-E-L-S" Defecation, Urinary incontinence, Miosis. Bradycardia/Bronchospasm/Bronchorrhea. Emesis, Lacrimation, Salivation.

11. Toxidromes 4. Opioids (codeine, morphine, meperidine, heroin): Bradycardia, hypotension, bradypnea. Hypothermia, hyporeflexia, pinpoint pupils. 5.Sedative-hypnotics (ethanol, benzodiazepines, barbiturates): Bradycardia, hypotension, bradypnea. Hypothermia, hyporeflexia, miosis.

13. A two year olds brought to the Pediatric Emergency Department by his mother following an ingestion of 20-22 cyproheptadine HCL tablets (4mg Periactin) 1-1.5 hours prior to presentation. According to his mother, the patient was acting "bizarre". VS: BP:130/70 P :160 T :98.4 Skin: Warm, dry, not flushed Neck: Supple Lungs: CTAB Heart: Tachycardic, otherwise WNL Abdomen: soft, NT Neurologic: Delerious. Patient grasping objects on the floor that were not present Unable to recognize mother, gait ataxic. DTR's normal, no focal findings.   Case 1

14. Antihistamine Toxicity (Anticholinergic Toxidrome) Management ABC's + supportive care. Sedation with benzodiazepines. Give false positive tricyclic immunoassay on urine screen hamper accurate diagnosis. Physostigmine not indicated unless patient's condition deteriorated. If hemodynamically stable, likely to respond well to sedation.

15. Case 2

16. Hydrocarbon Aspiration Management Most hydrocarbon ingestions of small volume. ABC's to prevent further aspiration, may need intubation for airway protection and /or progressive respiratory distress. Skin decontamination is needed, by removing his clothing and washing with gentle soap and water. Observe for signs of pneumonia , aspiration cause aseptic chemical pneumonitis does not require antibiotics. Secondary bacterial pneumonia may need treatment Prophylactic antibiotics NOT indicated. Steroids also NOT indicated. Supportive treatment with oxygen and bronchodilators to counteract bronchospasm.

18. Case 3

19. Acetaminophen ToxicityOpioid Toxicity Darvocet N-100 is a combination analgesic that contains propoxyphene, a synthetic opioid, and 650mg of acetaminophen. Synthetic opioids that do not cause significant miosis (others Demerol and Dextromethorphan) Many of synthetic opioids do not show up on routine urine tox screens. This scenario carries high possibility of additional unknown coingestants intentional overdoses often polydrug ingestions.

20. Acetaminophen ToxicityOpioid Toxicity Management Close attention to ABC's. Intubation if there risk of aspiration. For opioid toxicity: Naloxone (Narcan) to be given at initial dose of 2mg. Further doses given until adequate effect achieved. Naloxone provide rapid (1-2 minutes) reversal of symptoms. Due to short duration of naloxone action (60 minutes), re-dosing will likely be necessary ,if opioid symptoms persist. Lack of response to narcan might point to coingestion of another CNS depressant (benzodiazepines or barbiturates).

21. Acetaminophen ToxicityOpioid Toxicity For acetaminophen toxicity APAP level should be sent. 4 hour post ingestion level key in determining need for treatment. If level is toxic based on nomogram ,treatment with NAC should be initiated. If level is subtoxic, then to be repeated within 4 hours to confirm it . Initial loading dose of NAC within 8 hrs of ingestion, good effect if given within 24 hrs of ingestion. NAC Loading dose 140 mg, followed by 70 mg q4h X 17 doses.

23. Case 4

24. Lab work

25. Salicylate Toxicity Elevated anion gap metabolic acidosis (AG=34). A combination of primary AG metabolic acidosis + primary respiratory alkalosis highly suggestive of salicylate poisoning. A serum salicylate level > 60, indicates major exposure. Level > 100, indicates severe poisoning. Mental status + acid/base status more important than serum concentration. Bedside, quick urine test ferric chloride test. Presence of salicylates purple color change.

27. Management ABC's. Activated charcoal should be administered. Bicarbonate, both to correct the acidemia, and alkalinize the urine facilitate excretion of salicylates. Important to maintain serum potassium in normal range hypokalemia hamper efforts to alkalinize the urine. Dialysis to be considered for refractive acidosis or severe hypokelemia.

28. Tricyclic Antidepressants Significant source of poisonings. Toxic effects of TCA’s mediated through anticholinergic, alpha1 blockade, and quinidine-like Na channel blockade effects. TCA’s have low therapeutic to toxic ratio, doses < 10 times therapeutic sufficient to cause toxicity. Symptoms appear rapidly (within 1 hr of ingestion). Asymptomatic person for 6 hrs post ingestion unlikely to develop life-threatening events.

30. Diagnosis Urine screens can detect many of TCA’s, but a negative screen doesn’t rule out exposure. ECG key element to diagnose TCA toxicity. QRS prolongation + seizures + lethargy or coma , highly suggestive of TCA poisoning. Degree of QRS prolongation severity of CNS + cardiovascular toxicity. QRS >0.10 associated with seizures and >0.16 associated with arrhythmias.

32. Management ABC’s Activated charcoal. Unlike pure anticholinergic toxicity, physostigmine should NOT be used  in TCA overdose worsen seizures + conduction disturbances + increased risk for asystole. Most important therapy for TCA overdose sodium bicarbonate, QRS prolongation or hypotension. Initial dose 1 mEq/kg, repeated as boluses to maintain QRS < 0.10.  Asymptomatic pts monitored for at least 6 hours, symptomatics should be admitted to ICU for at least 24 hours.

33. Beta BlockersCalcium Channel Blockers Beta Blockers Have negative inotropic + chronotropic effects. In toxic doses, myocardial depressant effects predominate (hypertension, ventricular arrhythmias). Calcium Channel Blockers Have negative inotropic + chronotropic effects , and/or vasodilation, depends on site of action.

35. Manifestations Toxic doses for both classes varies from agent to agent. Both beta blockers and calcium channel blockers have very small therapeutic to toxic ratio. Signs of toxicity within therapeutic range. Most common features of overdose of both classes hypotension + bradycardia. ECG's show simply sinus bradycardia, with vaiable PR prolongation. Beta blockers QRS prolongation, but calcium channel blockers not.

36. Manifestations

37. Management ABC’s Activated charcoal . Gastric lavage for significant ingestions( within 1/2 -1 hr of ingestion). Sustained release preparations may need whole bowel irrigation. No place for dialysis. Focused Therapy -- Beta Blockers Glucagon is antidote. Has positive inotropic + chronotropic. Given as bolus followed by continuous infusion. Epinephrine also effective. QRS prolongation treated with sodium bicarbonate.

38. Management Focused Therapy -- Calcium Channel Blockers Calcium is antidote, helps to overcome the blockade of calcium channels. Given either as calcium chloride or calcium gluconate, repeated as needed. Calcium gluconate preferable (tissue damage with calcium chloride) 30 mL of calcium gluconate approximately 1 gram of calcium. Leads to rapid improvement in contractility, but no effect on conduction disturbances, sinus node depression or peripheral vasodilation. Glucagon and epinephrine beneficial in treating severe hypotension and/or bradycardia.

39. Take Home Message Prevention is always better than treatment. As early as the diagnosis and intervention as better as the results. Detailed history + Thorough examination + Reliable source + Little knowledge about toxicology Successful management.

40. Discussion