Small Doses, Big Problems: Deadly Pediatric Poisons

Transcription

1 Small Doses, Big Problems: Deadly Pediatric Poisons Adam Algren, MD Departments of Pediatrics and Emergency Medicine Children s Mercy Hospital and Truman Medical Center Medical Director University of Kansas Hospital Poison Control Center

2 Objectives Identify agents and medications classes that are potentially lethal in small doses Review the clinical presentation and evaluation of these poisonous agents Discuss management strategies for treating toxicity associated with these agents

3 One pill (or a small amount) can kill Sulfonylureas Ethylene Glycol/Methanol Calcium channel blockers Salicylates Opioids Clonidine Benzocaine Tricyclic antidepressants

4 Sulfonylureas Commonly prescribed for treatment of Type 2 diabetes 2009 AAPCC NPDS single substance sulfonylurea exposures 922- children < 6 years old 386 moderate outcomes, 38 major outcomes 1 death Bronstein AC, et al. Clin Toxicol. 2010;48:

5 Sulfonylureas Spiller HA, et al. Am J Health Syst Pharm. 2006;63:

6 Sulfonylurea pharmacology Calello DP, et al. J Med Toxicol. 2006;2:19-24

7 Sulfonylurea toxicity Hypoglycemia Agitation, tremor, headache, tachycardia, diaphoresis, lethargy, seizure, coma How much is too much? How long do children need to be observed?

8 Is one pill a problem? Hypoglycemia in 3 patients (ages 1-11) Glyburide 2.5mg, Glyburide 5mg, Glipizide 5mg Hypoglycemia in a 2 year old 5mg Glipizide Hypoglycemia in a 23 month old 5mg Glyburide Hypoglycemia in a 6 year old 10 mg Glipizide XL Hypoglycemia in an 11 month old 2 mg Glimepiride Quadrani DA, et al. J Toxicol Clin Toxicol. 1996;34: Szlatenyi CS, et al. Ann Emerg Med. 1998;31:773-6 Osterhoudt KC. Pediatr Case Reviews 2003;4:215-7 Pelavin PI, et al. J Pediatr Endocrinol Metab. 2009;22:171-5 Lung DD, et al. Pediatrics. 2011;127:e

9 How long should children be observed? 93 patients, 1-16 years old 25 developed hypoglycemia Mean time of onset 4.3 hours ( hours) 4 patients developed late hypoglycemia 185 patients, 10mo-11 years old 56 developed hypoglycemia 3 patients developed late hypoglycemia Quadrani DA, et al. J Toxicol Clin Toxicol. 1996;34: Spiller HA, et al. J Pediatr. 1997;131:141-6

10 How long should children be observed? 1,943 patients, < 6 years old 300 developed hypoglycemia 221 included in time-of-onset analysis Onset of hypoglycemia No food or dextrose 2 hours (0.5-7 hours) Food 5.9 hours (1-18 hours) (p<0.01) Dextrose 5.7 hours (1.5-9 hours) (p<0.01) Both food and dextrose 8.9 hours ( hours) (p<0.01) Lung DD, et al. Pediatrics. 2011;127:e

11 Lung DD, et al. Pediatrics. 2011;127:e

12 Dextrose Octreotide Somatostatin analog Treatment

13 Octreotide mechanism of action Calello DP, et al. J Med Toxicol. 2006;2:19-24

14 Octreotide Dose 1 mcg/kg SQ Consider repeat dose after 6 hours Adverse Effects Nausea, vomiting, diarrhea, abdominal pain Anaphylactoid reaction 2 year old developed urticaria following 1 mcg/kg SQ Bradycardia Tenenbein MS. Clin Toxicol. 2006;44:707 Chew T, et al. Clin Toxicol. 2008;46:636

15 Octreotide evidence: case series Octreotide: An Antidote for Sulfonylurea- Induced Hypoglycemia McLaughlin SA, et al. Ann Emerg Med. 2000;36:

16 McLaughlin SA, et al. 9 patients Ages Glyburide, 3 Glipizide 6 intentional, 3 therapeutic dosing

17 McLaughlin SA, et al. Ann Emerg Med. 2000;36:133-8

18 Octreotide evidence: Randomized controlled trial Comparison of Octreotide and Standard Therapy Versus Standard Therapy Alone for the Treatment of Sulfonylurea- Induced Hypoglycemia Fasano CJ, et al. Ann Emerg Med. 2008;51:

19 Fasano CJ, et al. > 18 yoa, documented hypoglycemia (<60 mg/dl), current sulfonylurea use Treatment randomized 75 mcg Octreotide SQ 22 patients Placebo SQ 18 patients

20 Ann Emerg Med. 2008;51:

21 Ethylene Glycol Toxic alcohols Anti-freeze, de-icing agent, glass cleaners 2009 AAPCC NPDS 5,404- single substance exposures 530- < 6 years of old 461 moderate outcomes, 224 major outcomes 19 deaths Bronstein AC, et al. Clin Toxicol. 2010;48:

22 Methanol Toxic alcohols Windshield washer fluid, de-icing agent, solvents, toy engine fuels, carburetor cleaner 2009 AAPCC NPDS 1,719- single substance exposures 394- <6 years old 94 moderate outcomes, 33 major outcomes 10 deaths Bronstein AC, et al. Clin Toxicol. 2010;48:

23 Ethylene glycol & methanol metabolism

24 How much is too much? Ethylene Glycol ml/kg = (0.6L/kg x 20mg/dl) / (product conc % x 1.12g/ml) 10.7/product concentration % 2 year old, 10kg, child ingesting small swallow (5ml) of 95% ethylene glycol could obtain serum level of 88 mg/dl! Methanol 0.2 ml/kg of 100% concentration Caravati EM, et al. Clin Toxicol. 2005;43:327-45

25 Ethylene glycol Clinical presentation Intoxication, metabolic acidosis, renal failure, coma, seizures, CN palsies, cerebral edema Methanol Intoxication, metabolic acidosis, optic nerve edema, blindness, basal ganglia ischemia

26 Osmolar gap Osm gap= Measured osm-calculated osm How can the osmolar gap help you? Rapid turnaround Osmolar gap >10 could suggest toxic alcohol ingestion How can a normal osmolar gap hurt you? Wide range of normal osmolar gaps (-2 ± 6) Less osmotically active alcohols may not elevate the osmolar gap >10 Time of ingestion must be considered in interrpreting osmolar gap McQuillen KK, et al. Acad Emerg Med. 1999;6:27-30

27 Time of ingestion vs. anion/osmolar gaps anion gap osmolar gap Mycyk MB, Aks SE. Am J Emerg Med. 2003;21:333-5

28 Management Supportive care Decontamination Consider NG lavage if < 1 hour after ingestion Activated charcoal only for co-ingestants Alcohol dehydrogenase inhibition Sodium bicarbonate Hemodialysis Barceloux DG, et al. Clin Toxicol. 1999;37:537-60

29 Fomepizole Potent ADH inhibitor More predictable kinetics than ethanol Easier dosing Doesn t require intensive monitoring Minimal adverse effect profile Rash Eiosinophilia Mild AST/ALT elevations Nystagmus

30 Calcium channel blockers Prescribed for hypertension, arrhythmias, migraines 2009 AAPCC NPDS 5,027- single substance ingestions 1,519- <6 years old 397 moderate outcomes, 62 major outcomes 16 deaths Bronstein AC, et al. Clin Toxicol. 2010;48:

31 CCB classifications Phenylalkylamine Verapamil Benzothiazepine Diltiazem Dihydropyridines Nifedipine, Isradipine, Amlodipine, Felodipine, Nimodipine, Nicardipine

32 Cardiac physiology 1 X 2 3

33 How much is too much? Olson KR, et al. Clin Toxicol. 2005;43:

34 Clinical presentation Bradycardia Dihydropyridines may induce reflex tachycardia Hypotension Conduction delays Hyperglycemia Inhibit insulin release from pancreatic β cells Acute lung injury

35 Management Vascular access Cardiac monitoring Labs/EKG Consider GI decontamination Gastric lavage Activated charcoal Whole bowel irrigation Normalize ph

36 Management IV fluids Atropine Norepinephrine Glucagon Calcium Cardiac Pacing IABP/ECMO High-dose insulin IV lipid emulsion

37 Inotropic High-dose insulin Stress induces heart to switch from FFA to carbohydrates for energy Insulin improves myocardial glucose utilization Clinical Experience > 50 case reports/case series Boluses ranged from units/kg Infusion rates units/kg/hour HR less responsive than BP/contractility Mean infusion duration 31 hours ( hours) Kerns W, et al. Emerg Med Clin N Am. 2007;25: Engebretsen KM, et al. Clin Toxicol. 2011;49:277-83

38 Dosing High-dose insulin 1 unit/kg bolus of regular insulin units/kg/hour Administer dextrose if glucose <400 mg/dl Adverse Effects Hypoglycemia Incidence % Monitor every 15 minutes initially Hypokalemia Monitor K every hour initially Only replace if <3 meq/l Kerns W, et al. Emerg Med Clin N Am. 2007;25: Engebretsen KM, et al. Clin Toxicol. 2011;49:277-83

39 IV lipid emulsion 17 year old, unresponsive at home Ingested ~ 8 grams buproprion, 4 grams lamotrigine 5 hours prior EMS- CGS 3, HR 112, BP 108/72, RR 8 ED- CGS 6, VSS, EKG- QRS 122 msec, QTc 485 msec 4 hours later PEA arrest ACLS, epi, amiodarone, Mg, sodium bicarb, defibrillation Transient ROSC after 20 min then recurrent PEA IV lipid emulsion after 52 min, ROSC within 1 min At hospital discharge Talkative, slight tremor/memory/fine coordination problems Sirianni AJ, et al. Ann Emerg Med. 2008;51:412-5

40 IV lipid emulsion Mechanism of action Lipid sink/sponge Enhanced intracellular energy metabolism Calcium channel activation Animal data bupivicaine, clomipramine, propranolol, verapamil, amitriptyline, nifedipine Human data Local anesthetics, CCB, BB, lamotrigine, buproprion, tricyclic antidepressants

41 IV lipid emulsion Dosing 1.5 ml/kg over 2 minutes Repeat if necessary 0.25 ml/kg/min for 1 hour Adverse Effects No significant adverse events reported with brief infusions Prolonged infusions Pulmonary shunting, fat overload syndrome Avoid in those with: egg allergy, fat metabolism disorder, liver disease