small doses, big problems: deadly pediatric poisons · small doses, big problems: deadly pediatric...
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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
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
One pill (or a small amount) can kill
Sulfonylureas
Ethylene Glycol/Methanol
Calcium channel blockers
Salicylates
Opioids
Clonidine
Benzocaine
Tricyclic antidepressants
Sulfonylureas
Commonly prescribed for treatment of
Type 2 diabetes
2009 AAPCC NPDS
1769- single substance sulfonylurea exposures
922- children < 6 years old
386 moderate outcomes, 38 major outcomes
1 death
Bronstein AC, et al. Clin Toxicol. 2010;48:979-1178
Sulfonylureas
Spiller HA, et al. Am J Health Syst Pharm. 2006;63:929-938
Sulfonylurea pharmacology
Calello DP, et al. J Med Toxicol. 2006;2:19-24
Sulfonylurea toxicity
Hypoglycemia
Agitation, tremor, headache, tachycardia,
diaphoresis, lethargy, seizure, coma
How much is too much?
How long do children need to be
observed?
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;34:267-70
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:e1558-64
How long should children be observed?
93 patients, 1-16 years old
25 developed hypoglycemia
Mean time of onset 4.3 hours (0.5-16 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;34:267-70
Spiller HA, et al. J Pediatr. 1997;131:141-6
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 (2.5-15 hours) (p<0.01)
Lung DD, et al. Pediatrics. 2011;127:e1558-64
Lung DD, et al. Pediatrics. 2011;127:e1558-64
Treatment
Dextrose
Octreotide
Somatostatin analog
Octreotide mechanism of action
Calello DP, et al. J Med Toxicol. 2006;2:19-24
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
Octreotide evidence: case series
Octreotide: An Antidote for Sulfonylurea-
Induced Hypoglycemia
McLaughlin SA, et al. Ann Emerg Med.
2000;36:133-138.
McLaughlin SA, et al.
9 patients
Ages 20-65
6 Glyburide, 3 Glipizide
6 intentional, 3 therapeutic dosing
McLaughlin SA, et al. Ann Emerg Med. 2000;36:133-8
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;51:400-406.
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
Ann Emerg Med. 2008;51:400-406
Toxic alcohols
Ethylene Glycol
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;48:979-1178
Toxic alcohols
Methanol
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;48:979-1178
Ethylene glycol & methanol metabolism
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
Clinical presentation
Ethylene glycol
Intoxication, metabolic acidosis, renal failure,
coma, seizures, CN palsies, cerebral edema
Methanol
Intoxication, metabolic acidosis, optic nerve
edema, blindness, basal ganglia ischemia
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
Time of ingestion vs. anion/osmolar gaps
------- anion gap
osmolar gap
Mycyk MB, Aks SE. Am J Emerg Med. 2003;21:333-5
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
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
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;48:979-1178
CCB classifications
Phenylalkylamine
Verapamil
Benzothiazepine
Diltiazem
Dihydropyridines
Nifedipine, Isradipine, Amlodipine,
Felodipine, Nimodipine, Nicardipine
Cardiac physiology
1
2
3
X
How much is too much?
Olson KR, et al. Clin Toxicol. 2005;43:797-822
Clinical presentation
Bradycardia
Dihydropyridines may induce reflex tachycardia
Hypotension
Conduction delays
Hyperglycemia
Inhibit insulin release from pancreatic β cells
Acute lung injury
Management
Vascular access
Cardiac monitoring
Labs/EKG
Consider GI decontamination
Gastric lavage
Activated charcoal
Whole bowel irrigation
Normalize pH
Management
IV fluids
Atropine
Norepinephrine
Glucagon
Calcium
Cardiac Pacing
IABP/ECMO
High-dose insulin
IV lipid emulsion
High-dose insulin
Inotropic
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 0.1-10 units/kg
Infusion rates 0.015-22 units/kg/hour
HR less responsive than BP/contractility
Mean infusion duration 31 hours (0.75-96 hours)
Kerns W, et al. Emerg Med Clin N Am. 2007;25:309-31
Engebretsen KM, et al. Clin Toxicol. 2011;49:277-83
High-dose insulin
Dosing
1 unit/kg bolus of regular insulin
0.5-10 units/kg/hour
Administer dextrose if glucose <400 mg/dl
Adverse Effects
Hypoglycemia
Incidence- 10-20%
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;25:309-31
Engebretsen KM, et al. Clin Toxicol. 2011;49:277-83
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
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
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