Transcript Alice in wonderland and other pediatric toxicological

R. Arbeau
S. Anderson
October 21/ 2010
Case 1
ID: 3 y/o F
 CC: Ingestion
 HPI: Was at grandmothers house.
Grandmother was gardening and thinks
patient ingested something
 Pmhx: Healthy
 Rx: Nil
 All: NKDA

Case 1 cont....

O/E
 BP: 98/64
 HR: 106
 RR: 22
 02: 100% on R/A
 T: 37.1
 Glucose: 4.5
Case 1 cont...
Exam:
 GCS 15. Acting appropriately.
 CV: N heart sounds
 Resp: N
 GI: N
 CNS: N

Case 1 cont...

B/W
 CBC, lytes, BUN, Cr N
 Tox screen?

EKG
 NSR
Case 2
ID: 17 month old
 CC: ? Ingestion
 HPI: Was at grandmothers house and
became fatigued. Taking lots of naps
since 15:00. Presented at 21:00
 Pmhx: similar presentation 3 weeks ago
 Rx: nil
 All: NKDA

Case 2 cont....

O/E:
 BP: 98/70
 HR: 73
 RR: 22
 02: 100% on R/A
 T: 37.4
 Glucose: 5.1
Case 2 cont...
O/E:
 Fatigued but easily rousable
 CV: heart sounds normal
 Resp: N
 GI: N
 CNS: No focal abnormalities

Case 2 cont...

B/W
 CBC, lytes, BUN, Cr N

EKG
 Sinus bradycardia
 No QTC/QRS changes
Approach to Toxicology
ABC’s
 IV
 O2
 Monitor

Approach Cont...

History
 Collateral history VERY important
○ DPV
○ Paramedic reports
○ Witnesses

Physical
 Track marks
 Pill fragments
 Look in pockets
Approach cont....
Supportive measures
 Antidotes
 Call Poison Control

What is a poison?
Kitchen/Laundry Area
Bathroom
Garage/Basement/Storage
Ammonia
Air Fresheners
Antifreeze*
Bleach
After-Shave Lotions
Insect Killers*
Carpet/Upholstery cleaners
Colognes/Perfumes
Fertilizers
Dishwasher Detergents
False Fingernail Removers*
Gasoline
Disinfectants
Hair Remover
Glues
Drain Cleaners*
Hair Styling Products Lotions/Creams/Oils
Kerosene
Fabric Softeners
Floor Cleaners
Furniture Polishes
Insect Killers*
Hand Sanitizer*
Makeup
Medications*
Mothballs
Lighter Fluids
Lime*
Lye*
Paints
Laundry Detergents
Mouthwash*
Paint Thinners
Metal Cleaners
Nail-Polish Removers
Pool Supplies
Oven Cleaners*
Rust Removers
Scouring Powders
Rubing Alcohol*
Shampoos
Shaving Creams
Rodent Killers
Turpentines
Weed Killers*
Spot Removers
Soaps/Deodorants
Windshield Wiper Fluids*
Spray Starches
Toilet Bowel Cleaners*
Ingestions
The dose is dependent upon
* The environmental concentration
* The properties of the toxin
* The frequency of exposure
* The length of exposure
* The exposure pathway
Toxicological Principles
Decrease absorption
 Enhance elimination
 Antidotes

Considerations

Change from normal state
 could be on the molecular, cellular, organ, or
organism level--the symptoms
Local vs. Systemic
 Reversible vs. Irreversible
 Immediate vs. Delayed

Further Consideration

Routes and Sites of Exposure
 Ingestion (Gastrointestinal Tract)
 Inhalation (Lungs)
 Dermal/Topical (Skin)
 Injection
○ intravenous, intramuscular, intraperitoneal
Why is pediatrics different?
Higher mg/kg dosing based on
bodyweight
 Exploratory behaviour

 Everything goes into their mouths
Pediatric Toxicology

One pill killers
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TCA’s
Antimalarials
Typical antipsychotics
Antidysrythmics
Ca2+ channel blockers
Beta blockers
Opiates (especially long acting)
Sulfonyureas (ie./ glyburide)
Theophylline
Lomotil (immodium)
Clonidine
One sip killers
Ethylene glycol
 Methanol
 Camphor
 Anything containing methylsalicylate

 Oil of wintergreen (100% methylsalicylate)
 Ben gay
○ 1 ml of 98% methylsalicylate contains 1.4 g of
salicylate
○ One teaspoon (5ml is potentially fatal in 2 year
old)
Bradycardia in pediatric tox
Calcium channel blockers
 Beta blockers
 Digoxin
 Cholinergic compounds (Increased
vagal tone)
 Opiates (related to sedative effect)
 Clonidine

 Includes visine (eye drops) and nasal spray
(afferin)
Back to cases

Case 1:
 3 y/o asymptomatic
 Took one of grandmothers 100 mg atenolol
Cases

Case 2:
 17 month old
 Bradycardic
 Fatigued
 Took 0.1 mg of grandmothers clonidine
Beta blockers
Uses: HTN, dysrhythmias, migraines
etc...
 Preparations: Oral immediate and
sustained release, IV, opthalmic
 Selective (B1 – heart, eye, kidney) or
non-selective (B1 and B2
{smooth/skeletal muscle, liver, heart})
 Selectivity is lost in overdose situations

Beta blockers cont...

Pharmacokinetics
 May be hepatic (propanolol) or renal
elimination (atenolol, nadalol)
 Onset is variable and may be delayed if
extended release formula
Beta Blockers cont...

Clinical Manifestations
 Safer ingestion in younger people (those not





dependant on adrenergic tone)
Hypotension, bradycardia, CHF
Conduction disturbances (SA and AV nodal
blockade, QRS prolongation and QTC
prolongation-sotalol)
Respiratory depression
Delirium, coma or seizures (often in context of
hypotension)
More worrisome if underlying disease or coingestions
Beta Blockers cont...

Hypoglycemia may occur
 Sympathetic stimulation is blocked
 Gluconeogenesis is impaired so glucose
may be low

Bronchospasm
 Underlying lung disease

Hyperkalemia may occur
 Cause K+ efflux as beta agonists cause K+
influx
Beta Blocker Management
ABC/IV/O2/Monitor
 Activated charcoal

 0.5-1 g/kg
 Most effective if given within one hour of
ingestion (no evidence)
 Multiple doses have been recommended but
no specific evidence
Beta Blocker Management cont...

Glucagon
 Inotropic and chronotropic effects
 Counteracts any hypoglycemia that may
occur
 5 to 10 mg IV bolus
 Infusion may be needed

Atropine
 Symptomatic bradycardia
 0.5 mg for adults
 0.02 mg/kg for children (minimum 0.1 mg)
Beta Blocker management cont….
Calcium
 Pressors
 Pacing

Beta Blocker Management cont...
If asymptomatic for 6 hours after an oral
overdose of normal release preparations
patients may be cleared medically
 Sustained release preparations should
be admitted to a monitored bed, but are
unlikely to develop toxicity if
asymptomatic for 24 hours (ie./
carvedilol, sotalol)
 Any hypotension, dysrhythmias should
be admitted to ICU/CCU bed

Calcium Channel Blockers

Pathophysiology:
 Inhibit L-type Ca2+ channels
○ Decreases calcium influx into myocardial and
smooth muscle cells
○ Myocardium: Decreased contractility and
conduction
○ Peripheral: Relaxation and vasodilation of
vasculature
CCB’s pathophysiology cont..
 Different affinities
○ Verapamil: greatest effects at SA and AV
nodes
○ Nifedipine: Greater effects peripherally than
on myocardium
○ Diltiazem: Moderate affinity for both
myocardial and peripheral cells
Ca2+ channel blockers cont...

Clinical Manifestations
 Hypotension
 Bradycardia
 AV conduction delays and complete heart block
 Cardiogenic shock
 Hyperglycemia
○ L-type calcium channels are blocked in pancreatic
islet cells leading to decreased insulin release
 CNS
○ Related to hypoperfusion
○ Noted to not have as much CNS effects as other
bradycardic medications (unsure of mechanism)
Ca2+ channel blockers cont...

Management
 ABC/IV/O2/Monitor
 Activated charcoal
○ 0.5-1 g/kg
○ Most effective if given within one hour of
ingestion
○ Multiple doses have been recommended
especially for extended release preparations
Ca2+ channel blockers cont...

Atropine
 Symptomatic bradycardia
○ May not work well b/c AV nodal blocking effects

Calcium
 Increases extracellular calcium creating a
concentration gradient promoting influx of Ca2+
into cells
 Contraindicated with digoxin co-ingestion
 Dosing 1g CaCl- or Ca gluconate
○ Initially 1-2 ampules
○ CaCl- provides three times as much calcium
(more sclerosis of vessels – better suited for
central venous administration)
Ca2+ channel blockers cont...

Glucagon
 Activates adenyl cyclase through glucagon
receptor
 Unlikely to be helpful but consider with
refractory hypotension

Pressors
 NE has theoretical advantage
○ B1 adrenergic activity reverses myocardial
depressant effects
○ Alpha1 effects increase peripheral vascular
effects
Ca2+ channel blockers cont...

Insulin/glucose
 Insulin may increase cardiac inotropy and
chronotropy
○ Has pressor effects that increases BP and HR

Pacing
CCB management
NEJM, Vol 344, No. 22, May, 2001
Case report of calcium channel blocker
OD’s being treated with insulin infusion
 L-type channels are blocked (including
islet cells) resulting in hypoinsulinemia
 In an unstressed state myocytes oxidize
FFA’s for energy, but in a stressed state
the hypoinsulinemia may prevent
glucose uptake by myocytes causing a
loss of inotropy, PVR and shock

CCB management
NEJM, Vol 344, No. 22, May, 2001
These patients were started on insulin
infusions which improved inotropy and
peripheral vascular resistance
 Also thought to improve acidosis by
improving uptake of carbohydrates by
myocytes and smooth muscle cells

Ca2+ channel blockers cont...

Disposition
 If asympomatic for 6 hours then may be
medically cleared
 Any hypotension or dysrythmias should be
admitted
Digoxin
Cardioactive steroid
 Uses: CHF, controlling ventricular
response in a-fib/a-flutter
 Mechanism of action

 Increases vagal tone (bradycardia and
impaired AV node conduction)
 Inhibits sodium potassium exchange pump
Digoxin

Naturally occurring sources
 Foxglove
 Lily of the valley
 Bufo toads
 Oleander/yellow oleander
 Dogbane
Digoxin



The Na/K+ exchange is blocked, thereby
decreasing Na+/Ca2+ exchange
In OD there is ++ intracellular Ca2+
Increases intracellular resting membrane
potential and increases dysrhythmias
Digoxin

Clinical manifestations
 GI: nausea, vomiting usually first symptom
 CNS: lethargy, confusion and weakness.
Halos, yellow vision in chronic overdose
situations
 Metabolic: Hyperkalemia is a marker for
severe poisoning in acute overdose this is
due to blockage of Na/K ATPase, release of
K+ from tissues and inhibition of K+ uptake
into skeletal muscle
Digoxin

Cardiac manifestations
 Increased automaticity with a high degree
AV block
 Any dysrhythmia is possible except a rapidly
conducted supraventricular rhythm with a
rapid ventricular rate (unless patient has a
congenital accessory pathway)
 Most common disturbance is PVC’s
 Bidirectional V-tach is rare, but
pathognomonic
Digoxin EKG
Digoxin – Bidirectional V-tach
Digoxin

Treatment
 Supportive
 Charcoal
 Atropine if indicated
 Avoid internal electrical pacing
○ May trigger fatal dysrhythmia
 Potassium/Magnesium if low
○ Magnesium contraindicated in bradycardia/AV
block
Digoxin

Definitive Treatment:
 Digibind
○ Digoxin specific antibody fragments
○ Binds digoxin in serum, diffuses into interstitial
sites and creates a concentration gradient to
help digoxin dissociate from the heart
Digoxin: Digibind
Indications: Adults
 Ventricular

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
dysrhythmia
Hemodynamically
significant
bradydysrhythmias not
responsive to atropine
Serum potassium >
5.0
Rapidly progressive
rhythm disturbances
and rising potassium
Co-ingestion of other
cardiotoxic drugs
Ingestion of plant
known to contain
cardiac glycosides
Acute ingestion of
greater than 10 mg

Indications: Children
 Ingestion of greater than
0.1-0.3 mg/kg plus
rapidly progressive
symptoms or potentially
life-threatening
dysrhythmias or
conduction blocks
 Co-ingestions of other
cardiotoxic drugs
 Ingestion of plant known
to contain cardiac
glycosides
Digoxin

Digibind dosing
-If dose ingested known
{amount ingested (mg) * 0.8}/ 0.5 (amount
digoxin bound/vial)
-If serum concentration known
{serum concentration * weight in kg} / 100
-Empiric dosing with unknown concentration
10 vials (adult or child)
Digoxin

Treatment
 Amiodarone if ventricular dysrhythmias
 ACLS management
○ Electricity may worsen rhythm, but is
obviously treatment of choice in arrest
situation
○ Digibind should also be considered if not
given already
Digoxin

Disposition:
 All patients who are symptomatic require at
least 12 hours of monitoring
 If digibind is required then an ICU/CCU
admission is required
Clonidine
 Central alpha agonist
○ Decreases NE release in brain, which
decreases sympathetic outflow causing
decreased HR, BP and cardiac output
 Peripheral alpha agonist
○ In overdose
○ Post-synaptic alpha2 adrenergic agonist on
peripheral vessels. This increases NE release
causing peripheral vasoconstriction which
may cause early transient hypertension
Clonidine

Clinical Manifestations
 CV: early transient hypertension followed by
hypotension and bradycardia from central
effects
 CNS: Lethargy, pinpoint pupils
 Respiratory: Hypoventilation, hypoxia,
periodic apnea, Cheyne Stokes respiration
Clonidine

Treatment




ABC/IV/O2/Monitor
Supportive
Charcoal
Naloxone: may reverse some or all of the
sedation associated (mechanism unclear). May
need large doses (ie./ 200 mg in 24 hours)
 For hypotension:
○ IV fluids initially
○ Atropine
○ Consider pressors in refractory hypotension
Clonidine
Admission if any symptoms for
monitoring
 Monitored for 6-8 hours if asymptomatic

Cholinergic Syndrome
Bradycardia may caused by action on
muscarinic receptors
 Should be easily recognized and
differentiated from other exposures

Bradycardia Comparison
Drug
Temp
BP
Pupil
s
CNS
K+
Skin
Bowe Urine
l
Glu. EKG
CCB
N/E
Dec
N/E
+/-
+/-
N/E
N/E
N/E
Inc
Brady
AV blocks
Bblock
N/E
Dec
N/E
Dec
Inc
N/E
N/E
N/E
Dec
Brady, AV
blocks
Dig
N/E
+/-
Halo
Dec
vision,
yellow
haze
Acute
Inc.
N/E
N/E
N/E
N/E
PVC’s,
Scooped
ST’s, bi
directional
VT
Chron
ic
Dec
Cholin N/E
ergic
+/-
miosis Dec
+/-
Wet
Inc
Urinat N/E
ion
Brady
Clonid N/E
ine
Dec
pinpoi Dec
nt
+/-
N/E
N/E
N/E
Brady
N/E
Back to cases

Case 1:
 3y/o F
 Took grandmothers atenolol
 Poison control contacted
 Given charcoal
 Remained asymptomatic
 Transferred to Peds ER for observation
 Discharged home after 6 hours of
observation
Cases

Case 2:
 17 month old
 Ingested 0.1 mg clonidine
 Fatigued, bradycardia
 Given charcoal
 Narcan was advised, but not given
 Atropine was given with minimal effect
 Admitted to PCCU and monitored for 36 hours
 HR increased with no further intervention
required
References



Rosens
Boyer & Shannon. Treatment of Calcium channel blocker
intoxication with insulin infusion. NEJM. Vol. 344, No. 22,
2001
New York City Poison Control Handbook
Questions?