Transcript Pediatric Poisoning

Pediatric Poisonings
Mark Sutter, MD
Overview
Epidemiology
Important Legislation
Packaging and Marketing Problems
Physiologic Differences
Iron
Pesticides
Deadly Pediatric Poisons
Epidemiology
US Poison Centers receive 1.5 million calls a
year regarding pediatric ingestions.
79% of these calls involve children younger than
age six.
56% of pediatric exposures are from products
around the house including medicines, cleaning
agents, pesticides, plants and cosmetics.
Epidemiology
99% of ingestions by children under 6 are
unintentional.
Approximately 40% of ingestions reported
to the poison center by adolescents are
intentional.
Approximately 56% of adolescent
ingestions are by females.
Epidemiology
Legislation
The Poison Prevention Packaging Act of
1970. (PPPA)
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Requires child protective packaging of
hazardous household products.
Over the last 30 years the list of substances
regulated by the PPPA have expanded to
include medicines, solvents, and oils.
Data shows reduction of 45% mortality of
pediatric patients since the introduction and
expansion of PPPA.
Special Pediatric Issues
ALL THINGS
TEND TO END
UP IN THE
MOUTHS OF
YOUNG
CHILDREN!!
Which is Candy?
Sweet Tarts vs. Ecstacy
Poison Center Campaign
Physiologic Differences
Blood brain barrier still more permeable to toxicologic substances
until around 4 months.
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No studies demonstrating increased permeability, rather this is an
estimate based on toxicity noted with smaller doses than expected.
Higher metabolic demands.
Decreased ability to glucuronidate in the infant period. Second
trimester pregnancies that were terminated showed only 10%
activity of the P-450 system.
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No better studies to date, but most believe between ages 2-4 years that
glucuronidation is equivalent to adults.
Decreased glycogen stores.
Physiologic Differences
Increased body surface area can lead to
thermoregulatory issues.
Children reside lower to the ground. This puts
them at higher risk for ingesting compounds
heavier than air. Often adults will NOT have the
same exposure.
Inability to avoid hazards – they do not read
warning labels or “Do Not Enter” signs.
Iron
The most common
cause of death in
toddlers.
Classically taught as
having five clinical
stages.
Remember prenatal
vitamins, supplements,
and “natural products”.
Iron
Toxic doses occur at 10-20mg/Kg of
elemental iron.
Prenatal vitamins typically contain about
65 mg of elemental iron.
Childrens vitamins contain about 10-18 mg
of elemental iron.
The Five Stages
Stage 1
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Nausea, vomitting, abdominal pain and diarrhea.
Stage 2
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This is the latent phase often between 6-24 hours as the patient
resolves GI symptoms.
Stage 3
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Shock stage involving multiple organs including coagulopathy,
poor cardiac output, hypovolemia, lethargy and seizures.
Stage 4
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Continuing of hepatic failure and ongoing oxidative damage by
the iron in the reticuloendothelial system.
Stage 5
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Gastric outlet obstruction secondary to scarring and strictures.
Management
Detailed history and physical including a rectal
exam for frank blood.
Aggressive fluid resuscitation and intravenous
access.
Whole bowel irrigation and KUB to look for pills.
Laboratory analysis for CBC, chemistry, and iron
levels (peak around 4 hours).
Will often require repeat levels with a repeat
chemistry.
TIBC has no utility in the acute overdose setting.
Management
Management
If the patient is in shock, remember to atleast
type and screen (if not cross match) for blood.
Give deferoxamine before iron level is back if the
patient is in shock.
Deferoxamine was derived from streptomyces
pilosus.
Hypotension and allergic reactions are seen.
ARDS is a known complication and usually limit
its use to 24 hours or less.
Pesticides
Specifically
organophosphates and
carbamates.
They work by inhibiting
acetylcholinesterase.
Present with
cholinergic symptoms
Cholinergic Symptoms
Nicotinic Symptoms
Remember the days of the week !
Mydriasis
Tachypnea
Weakness
Tachycardia
Fasiculations
Pediatric patients tend to present with a
predominance of nicotinic symptoms!!!
Weakness from Pesticides
Treatment
Atropine 0.02 mg / Kg IV. Repeat as needed
and titrate to respiratory secretions. It will
likely take massive doses!!
Pralidoxime (2-Pam) 20-40 mg / Kg bolus
followed by 10-20 mg / Kg /hour infusion.
Remember to send RBC and Plasma
Cholinesterase levels upon arrival and daily.
The Expanded “One Pill Kill”
The Deadly Pediatric Poisons
Calcium Channel
Blockers
Cyclic
Antidepressants
Lomotil
Opiates / Opiods
Salicylates (methyl)
Toxic Alcohols
Sulfonylureas
Camphor
Clonidine and
imidazolines
Antimalarials
Calcium Channel Blockers
Three major classes
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Phenylalkylamine
Benzothiazepine
Dihydropyridine
Block L-type channels
Cause hypotension,
bradycardia, and
arrythmias.
Immediate and sustained
release.
Usually not the childs
medication.
Calcium Channel Blockers
Manage A, B, C’s
Check Labs and EKG
Fluids
Calcium
Glucagon
Pressors
High Dose Insulin
Atorpine and Pacing
Calcium Channel Blockers
May be able to wean
pressors with insulin.
Insulin dosage is 1 unit /
kg bolus and 0.5 units /
kg / hour drip.
Monitor sugar Q20
minutes for the first few
hours.
Most will NOT become
hypoglycemic.
Cyclic Antidepressants
They were the leading cause of poisoning
fatality until 1993.
They interfere with reuptake of biogenic amines
and seratonin at the nerve terminal.
Manifest toxicity by anticholinergic effects,
alpha-1 inhibition, sodium channel blocade, and
can inhibit GABA.
Cause CNS and cardiovascular toxicity with
arrythmias leading to mortality.
EKG Findings
EKG Findings
Cyclic Antidepressant Managment
Manage A, B, C’s aggressively
Optimize electrolytes
Follow serial EKG’s and use Bicarb if:
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QRS >100 or 110 msec
aVr > 3 mm
If bicarbonate and magnesium are not effective,
lidocaine is the antidysrhythmic of choice.
Norepinephrine is the pressor of choice for
refractory hypotension.
Is it the Sodium or the Bicarb?
The answer is BOTH!
Sodium overcomes
the partial blockade
from cyclic
antidepressants.
Alkalinization does
change binding
properties.
How does the bicarb work?
Initially thought to increase protein binding thus
limiting free drug in the blood
Rat study using alpha-1 acid glycoprotein (AAG)
only decreased arrhythmias at massive doses.
AAG is a proven TCA binder.
Current theories is that the ionic form of the TCA
binds to the sodium channel causing blockade
and the bicarbonate changes the TCA from the
ionic form to the neutral form causing less
blockade.
Lomotil
Antidiarrheal agent containing both
diphenoxylate and atropine.
Both agents are absorbed by the GI tract and
absorption may be delayed in overdose due to
inhibitory effects on smooth muscle motility.
Diphenoxylate is an opoid that is metabolized to
difenoxin which is 5 times more potent than the
parent compound and has half life of 12-14
hours.
Lomotil
Patients manifest
signs and symptoms
of opiate toxicity.
Respond well to
naloxone and
supportive care.
Current
recommendations are
for a minimum of 24
hour observation.
Opiates / Opiods
Typically present with respiratory
depression, altered mental status, and
miosis.
Address the patient like any other “altered
mental status”
Key point is to remember to consider an
opiate ingestion.
Naloxone Dosing
Usually start with 0.01-0.1 mg / Kg.
Repeat as frequently as needed to reverse
symptoms.
If a drip is required, calculate how much
naloxone was used in the first hour and
start the drip at 2/3 that dose.
Salicylates
Pharmacology
Irreversibly inhibits the enzyme cyclooxygenase.
This inhibits prostaglandin synthesis.
Since prostaglandins are not synthesized, their
downstream byproducts are never released
such as: IL-6, TNF, and alpha and beta
interferons.
Believed to directly inhibit neutrophils to
decrease the inflammatory response.
Salicylate Metabolism
Pathophysiology
Salicylates stimulate the brainstem to cause
hyperventilation (respiratory alkalosis).
Multifactorial renal impairment leads to
accumulation of sulfuric and phosphoric acids.
Interfere with the Krebs Cycle limiting substrates
for ATP generation.
Pathophysiology Continued
Uncouples oxidative phosphorylation which
leads to increased pyruvic and lactic acid level
and generates heat.
Causes salicylate induced fatty acid metabolism
which produces ketone bodies. This
ketoacidosis contributes a significant portion to
the overall metabolic acidosis.
Clinical Manifestations
Early symptoms are usually non-specific such as nausea
and vomiting.
Tinnitus with or without hearing loss can also be an early
sign.
Hyperventilation is often a warning sign of a significant
ingestion.
CNS signs can vary from vertigo to hallucinations to
stupor. Coma is rare except in massive overdoses.
In large overdoses, almost every organ system becomes
involved.
Treatment
Address the A,B, C’s.
Detailed history and exam.
Laboratory evaluation and consider a blood gas
if your history suggests an ingestion.
Activated charcoal should be given. Evidence
for multidose charcoal is equivocal.
The use of sodium bicarbonate.
Measure serial salicylate levels and chemistries.
Sodium Bicarbonate Therapy
The goal is to titrate the urinary pH to 8.
Potassium must be monitored closely because if
the potassium drops, the kidney will retain the
potassium and excrete hydrogen.
Excretion of hydrogen will make it impossible to
titrate your therapy to a urinary pH of 8.
Indications for Hemodialysis
Renal failure.
Congestive heart failure (relative).
Acute lung injury.
Persistent CNS disturbance.
Severe acid-base or electrolyte imbalance,
despite appropriate treatment.
Hepatic compromise with coagulopathy.
Salicylate concentration (acute) >100 mg/dL.
Toxic Alcohols
Ethylene Glycol
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Antifreeze
Coolant Mixtures
Methanol
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Windshield wiper fluid
Moonshine
Ethylene Glycol and Methanol
fomepizole
folate
thiamine
Mg, B6
The Osmolar Gap
Clinical Symptoms
Treatment
Fomepizole or ethanol – both inhibit
alcohol dehydrogenase.
Cofactors
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Pyridoxime
Folate
Magnesium
Thiamine
Fomepizole Dosing
Loading dose
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15 mg / Kg
Next 4 doses
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10 mg / Kg
Subsequent doses
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15 mg / Kg
Dosing schedule is every
12 hours except during
dialysis. Then it is every
4 hours during dialysis as
it gets dialyzed off.
Key Toxic Alcohol Points
Send levels for toxic alcohols as soon as
possible and make them “STAT”.
Talk to nephrology early as preparing for dialysis
can take time. (especially in kids)
Remember to check serum osmolality and
calculate serum osmolarity.
Measured osms – ( 2X NA + glu/18 +bun/2.8 + etoh/4.6)
Sulfonylureas
Mechanism of Action
Sulfonylureas keep
the potassium efflux
channel closed.
This keeps the cell
depolarized which
allows the voltagegated calcium
channel to remain
open.
This stimulates insulin
release.
Sulfonylureas
Since sulfonylureas stimulate insulin release,
this can result in prolonged hypoglycemia.
Continued doses of dextrose will continue to
stimulate insulin release.
Octreotide works by antagonizing insulin
release. Exact mechanism is still being debated.
Octreotide
The dose is 1-2 mcg / Kg bolus IV.
Some papers suggest a continuous infusion
while others suggest an every 8 hour dosing
regimen.
If placed on an octreotide regimen, the
octreotide must be off a minimum of 24 hours
without another episode of hypoglycemia before
discharge.
Key Facts
A retrospective study showed 4 of 25
patients developed delayed hypoglycemia
including 1 at 16 hours post ingestion.
If a sulfonylurea is ingested, a minimum of
24 hours of observation is recommended.
Camphor
Aromatic ketone
derived from plants.
Acts as a topical
rubefacient.
Usually ingested as a
liquid.
Often in preparations
combined with other
medicines such as
salicylates.
Camphor
Initial symptoms are gastrointestinal
distress and generalized feelings of
warmth.
Symptoms usually progress quickly to
nervous system involvement from
restlessness to seizures.
Delayed seizures have been reported up
to 9 hours after ingestion.
Camphor
Ingestions of 1-2 grams have been fatal in
children.
A 19 month old died after ingesting 5 ml of 20%
camphorated oil.
Asymptomatic patients should be observed 6-8
hours and discharged if not developing
symptoms.
Remember about hydrocarbon aspiration if
product is an oil with a history of coughing or
vomitting.
Clonidine and imidazolines
Clonidine is an alpha-2 agonist that is
used for hypertension.
Imidazolines, such as oxymetazoline
(afrin) are used as decongestants.
Symptoms typically present like an opiate
overdose ?
Why?
? Like an Opiate Overdose ?
They are NOT structurally related to
opiates.
The alpha-2 receptor targeted by clonidine
has significant functional overlap with the
opiate receptor. Both may be located on
the same neuron, both coupled by via Gprotein to the same potassium channel.
May require larger doses of naloxone to
reverse symptoms.
Antimalarials
These include cloroquine, hydroxychloroquine,
quinine and their relatives.
They work by both sodium channel blockade as
well as blockade of the potassium rectifier
channel.
These lead to QRS widening as well as QT
prolongation.
Torsades is a known complication of overdose.
Symptoms
Small therapeutic index.
Presents with symptomatology known as
“cinchonism” which is tachycardia,
nausea, vomitting, hearing loss, tinnitus,
headache, vertigo, dystonia, and diarrhea.
Patients often known to have a flushed
appearance.
Treatment
These patients require aggressive
management of electrolytes.
If the QRS widens, treatment with sodium
bicarbonate is indicated.
Magnesium should be used for Torsades.
If ventricular arrythmias occur despite
optimal management, lidocaine is the
treatment of choice. (Avoid class 1a, 1c)
Selected Toxic Dosages
Summary
Remember the “Deadly Pediatric Poisons”
Don’t be fooled if the “look good” as
significant toxicity is still possible.
Contact the poison center early as
knowing the dosage and time of ingestion
can influence your management
Review Articles
Michael JB, Sztanjnkrycer MD. Deadly pediatric
poisons: nine common agents that kill at low doses.
Emergency Medicine Clinics of North America 2004;
(22): 1019-1050.
Bar-Oz B, Levichek Z, Koren G. Medications that can be
fatal for a toddler with one tablet or teaspoonful.
Pediatric Drugs 2004; 6(2): 123-126.