small doses, big problems: deadly pediatric poisons · small doses, big problems: deadly pediatric...

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)


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


19 deaths


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


10 deaths


Ethylene glycol & methanol metabolism


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


16 deaths


CCB classifications

Phenylalkylamine

Verapamil

Benzothiazepine

Diltiazem

Dihydropyridines

Nifedipine, Isradipine, Amlodipine,

Felodipine, Nimodipine, Nicardipine

Cardiac physiology

1

2

3

X


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

small doses, big problems: deadly pediatric poisons · small doses, big problems: deadly pediatric...

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