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Status Epilepticus in Children
Definitions
• Status Epilepticus: 30 minute duration of
seizures (or two or more sequential seizures
without full recovery of consciousness
between seizures). For practical purposes,
start treatment earlier
• Seizure: paroxysmal event characterized by
a change in behavior of the patient; it is
caused by abnormal and excessive activity of
a group of cortical neurons.
• Epilepsy: occurrence of two or more
unprovoked seizures
Status epilepticus
• Common in children, particularly in
children less than 2 years old
• Particularly common in children with
epilepsy (9-27% over time have at least
one episode of status)
• High morbidity and mortality
Complications
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Hypoxemia
Acidemia
Glucose alterations
Blood pressure disturbances
Increased intracranial pressure
Morbidity
– Neurologic sequelae
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• Mortality
– 3-4%
Focal motor deficits
Mental retardation
Behavioral disorders
Chronic epilepsy
Acute and chronic MRI changes
Assessment of the Patient with
Status Epilpeticus
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Determine if patient is having a seizure
Determine type of seizure
Determine possible etiology of seizure
Treat underlying etiology of seizure if
pertinent
5. Stop the seizure
Differential Diagnosis
Is patient having a seizure??
• Movement Disorder
– Drug induced dystonic reaction
– Paroxysmal dyskinesias
– Sandifers syndrome
• Breathholding spell
• Syncope
• Spasm
– Secondary to increased ICP
• Psychogenic seizure
• Narcolepsy (cataplexy)
Classification of seizures
Generalized
Partial
• loss of consciousness
• whole brain at onset
• no loss of consciousness
• focal onset
Convulsive
Complex Partial
• tonic clonic
• tonic
• clonic
• change in level of consciousness
Nonconvulsive
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absence
atypical absence
myoclonic
atonic
Simple Partial
• no change in consciousness
Partial Seizure evolving
to secondary
generalization
Etiology of Status Epilepticus
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Acute symptomatic
Remote symptomatic
Progressive encephalopathy
Febrile
Cryptogenic/Idiopathic
Acute Symptomatic Seizures
• Fever
• Infectious
– Meningitis
– Abscess
– Encephalitis
• Neurovascular
– Ischemic stroke
– Hemorrhagic stroke (AVM, aneurysm, etc)
• Trauma
• Tumor
• Metabolic
– Hypoglycemia
– Hypocalcemia
– Hyponatremia
Management of Status Epilepticus
in Children--Initial Approach
Status Epilepticus Working Party, 2000 (mostly)
• Initial assessment
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A, B, Cs
Rapid neurologic examination
Brief history
Give high flow oxygen
• Measure rapid blood glucose
– More to avoid glucose infusion than the uncommon hypoglycemic
seizures
• Confirm epileptic seizure
– Not all events are epileptic!!!!
• Laboratory Studies
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Glucose, electrolytes, calcium, magnesium
ABG
CBC
Serum anticonvulsant drug levels (if indicated)
Toxicology screening
Rapid Neurologic Evaluation
• Observation
– What is the patient doing
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What are the movements? Which extremities involved?
Stiff or floppy?
What are eyes doing? Head?
Is patient at all responsive?
• Mental Status
– Can you get the patient to respond? Verbal? Noxious
stimuli (not too noxious!)? Appropriate withdrawal?
• Cranial Nerves
– Pupil reactivity, extraocular movements
• Motor/Sensory:
– What parts of body are moving? What parts withdraw
to nailbed pressure
Brief history
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Has the child ever had a seizure before?
History of trauma? Fever? Ingestion?
Was the child his usual self prior to this event?
What medications (including nonprescription) does the
child take?
• Any medical problems?
• Any neurologic/developmental problems?
• If child has known epilepsy
– Name and dosage of medications!!! Calculate if this is
appropriate dosage.
– Has the child missed dosage of medication
• If so, consider loading with that medication
– Be aware of paradoxical side effects of ACDS
• Phenytoin and carbamazepine toxicity may precipitate SE
Management of Status Epilepticus
in Children--Initial Approach
• Initial assessment
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A, B, Cs
Rapid neurologic examination
Brief history
Give high flow oxygen
• Measure rapid blood glucose
– More to avoid glucose infusion than the uncommon hypoglycemic
seizures
• Confirm epileptic seizure
– Not all events are epileptic!!!!
• Laboratory Studies
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Glucose, electrolytes, calcium, magnesium
ABG
CBC
Serum anticonvulsant drug levels (if indicated)
Toxicology screening
No Caption Found
The Status Epilepticus Working Party, et al. Arch Dis Child 2000;83:415-419
Management of Status Epilepticus
in Children
1. Stop the seizure
2. Keep seizure from recurring
Treatment of Status Epilepticus:
1. STOP the seizure with benzodiazepine
– If no IV access: Diazepam 0.5 mg/kg PR
• Diastat
• IV diazepam, inserted per rectum through butterfly (needle cut off!)
– If IV access: Lorazepam
• 0.1 mg/kg IV over 30-60 seconds
• If seizures continue another 10 minutes, repeat lorazepam
– Midazolam: IV, buccal, nasal
2. ADD fosphenytoin (either as second medication if seizure refractory,
or to stop from recurring)
– 20 PE/kg IV
3. ADD third medication if necessary- Phenobarbital, Valproic
acid, Keppra
Benzodiazepines
• Diazepam vs. Lorazepam
• Diazepam
– Highly effective in rapidly terminating seizures
– However, redistribution into adipose tissue limits anticonvulsant
effect to less than 20 minutes
– Available in rectal gel, which can be given outside the ED
• Lorazepam
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Equally or more effective than diazepam
Longer duration of action (6-12 hours vs. <1 hour)
Less respiratory depression than diazepam
Not available rectally
Treatment of Status Epilepticus in the Child
Step 2
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ADD fosphenytoin:20 PE/kg over 7 min.
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If fosphenytoin not available, use phenytoin:
18-20mg/kg over 20 minutes
– General rule of thumb: for each 1 mg/kg
phenytoin (or 1PE/kg fosphenytoin) expect
level to rise by 1)
• If already on phenytoin, load with
phenobarbital 20mg/kg over 10 minutes
Phenytoin vs. Fosphenytoin
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Phenytoin
Can be diluted in NS only!
Maximum concentration of
10mg per ml
Infusion rate < 1 mg/kg/min
(Therefore 18 mg/kg is infused
over no less than 18 minutes)
Risk of hypotension and
cardiac arrythmia
Monitor heartrate BP and EKG
Extravasation reaction, purple
glove syndrome
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Fosphenytoin
Pro drug: converted into
phenytoin
Can be diluted in commonly
used diluents
Can infuse 3 times more
rapidly than phenytoin (ie, over
7-8 minutes)
Decreased risk hypertension
and arrhythmia
Decreased risk extravasation
reactions (pH of 8)
Dosed in phenytoin
equivalents (PE) which can be
confusing.
Treatment of Status Epilepticus in the Child
Step 3
• ADD third medication if necessary
– Phenobarbital 20mg/kg IV (2 mg/kg/min)\
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may repeat 10mg/kg every thirty minutes
Be prepared to intubate as barbituates and benzos potentiate each others
effects
– Valproic Acid
• Not yet approved for initial treatment of SE
• Dosage 20-40 mg/kg IV (diluted 1:1 with normal saline or 5% dextrose in
water) over 5-10 minutes; may repeat in 10-15 minutes; follow with IV
infusion of 5 mg/kg/hr
– Keppra
• Not approved for initial treatment of SE
Refractory Status Epilepticus
• Definition: continued seizures after 2 or 3 antiepileptic
drugs have failed
• Will usually need EEG monitoring at this point;
typically titrate to burst suppression
Managementof Refractory
Status Epilepticus in the Child
• Confirm this is truly an epileptic seizure
and continue to look for underlying
treatable cause
• Call for back up from anesthetist or
intensive care specialist
Treatment of Refractory Status
Epilepticus in the Child
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Inhalational anesthetics
Pentobarbital
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Propofol
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Midazolam
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Valproic acid
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Keppra
Consider IV pyridoxine
• Short acting; Significant side effects: respiratory depression, hypotension,
myocardial depression, reduced cardiac output, pulmonary edema, ileus;
Intubation and intravascualr monitoring usually required
• Thiopental
• Active metabolites which can accumulate; Possibly higher adverse reactions than
pentobarbital
• Intravenous anesthetic; Risk of hypotension, apnea and bradycardia
• Contraindicated in child on ketogenic diet
• Short half life; IV, IM, intranasal, PO, buccal or rectal
• 0.1-0.3 mg/kg IV followed by 1mcg/kg/min IV infusion; increase every 15 minutes
as necessary; maximum 8-10 mcg/kg/min
• 20-40 mg/kg IV (diluted 1:1with normal saline or 5% dextrose in water) over 5-10
minutes; may repeat in 10-15 minutes. Follow with IV infusion of 5 mg/kg/hr
Valproic acid
• Not yet approved for initial treatment of SE
• Appears effective and safe
• Dosage
– 20-40 mg/kg IV (diluted 1:1 with normal saline
or 5% dextrose in water) over 5-10 minutes;
may repeat in 10-15 minutes
– Follow with IV infusion of 5 mg/kg/hr
Propofol
– Intravenous anesthetic
– Small number of studies show effectiveness
– Risk of hypotension, apnea and bradycardia
– Contraindicated in child on ketogenic diet
Midazolam
– Short half life
– IV, IM, intranasal, PO, buccal or rectal
– Can be given as continuous IV infusion
for refractory SE
– Midazolam infusion
• 0.1-0.3 mg/kg IV followed by 1mcg/kg/min IV infusion.
• Increase every 15 minutes as necessary
• Maximum 8-10 mcg/kg/min
Pentobarbital
• Short acting; used for refractory SE
• Significant side effects: respiratory depression,
hypotension, myocardial depression, reduced cardiac
output, pulmonary edema, ileus
• Intubation and intravascualr monitoring usually required
• Thiopental
– Used for refractory SE
– Active metabolites which can accumulate
– Possibly higher adverse reactions than pentobarbital
Diagnostic assessment
Riveillo et al: Practice Parameter: Diagnostic assessment of the child with
status epilepticus (an evidence-based review) Neurology 2006;67:1542-1550
• CBC, electrolytes, calcium, glucose
• Anticonvulsant levels (if applicable)
• LP: only if there is clinical suspicion of meningitis
– If this is first febrile seizure, presenting as status, LP will usually
need to be performed
• Consider toxicology testing
• Metabolic and genetic testing: only if specific concern at
first seizure (eg: history of recurrent lethargy, etc)
• Consider neuroimaging:
– MRI better sensitivity, but may not be available
– CT better for evaluation of acute blood, skull fractures
• Obtain EEG (not in acute period)
Disposition
• Patient gets admitted for observation for
24 hours
Home treatments for Status
Epilepticus
• Diastat
– Dosage: 0.5 mg/kg, round up
– DIASTAT AcuDial
• 10mg delivery system with a 4.4 cm tip
(delivers doses of 5, 7.5 and 10 mg)
• 20 mg delivery system with a 6.0 cm tip
(delivers doses of 10, 12.5 and 20 mg)
• Twin Pack of 2 pre-filled configurations
(pharmacist locks in proper dosage)
• Intranasal midazolam
Neonatal Seizures
Neonatal Status Epilepticus
Etiology
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Hypoxic ischemic encephalopathy
CNS infection
Intracranial Hemorrhage
Cerebral Infarction
Chromosomal abnormalities
Congenital Brain abnormalities
Metabolic Distubances
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Hypoglycemia
Hypocalcemia
Hypomagnesemia
Pyridoxine dependency
• Inborn errors of metabolism
• Drug withdrawal or intoxication
Neonatal Seizures
Etiology
Time of Onset
Hypoxic ischemic encephalopathy
12-24 hour
Drug withdrawal
24-72 hour
Hypocalcemia (nutritional)
3-7 days
Aminoaciduria/organic aciduria
3-7 days
Differential Diagnosis of Neonatal Seizures by
Peak Time of Onset
Fenichel, 2nd ed.
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24 hours
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72 hours – 1 week
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Meningitis/Sepsis
Direct drug effect
Hypoxic-ischemic encephalopathy
Intrauterine infection
Laceration of tentorium or falx
Pyridoxine dependency
Subarachnoid hemorrhage
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24-72 hours
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Familial neonatal seizures
Cerebral dysgenesis
Cerebral infarction
Hypoparathyroidism
Intracerebral hemorrhage
Kernicterus
Nutritional hypocalcemia
Methylmalonic/ propionic acidemia
Urea cycle abnormalities
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Meningitis/sepsis
Drug withdrawal
Cerebral contusion/SDH
Cerebral dysgenesis
IVH in newborns
Pyridoxine dependency
Subarachnoid hemorrhage
Urea cycle abnormalities
Hypoparathyroidsm-hypocalcemia
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1 week- 4 weeks
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Neonatal adrenoleukodystrophy
Cerebral dysgenesis
Fructose dysmetabolism
Gaucher Type 2
Gm1 gangliosidosis
Herpes simplex encephalitis
MSUD
Urea cycle abnormalities
Diagnostic Assessment of Neonatal
Seizures
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Metabolic testing (screening)
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LP
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Blood glucose
Calcium
Ammonia
Lactate
pH
electrolytes
Cells
Protein/glucose
Cultures
Herpes PCR
Lactate/pyruvate
Aminoacids
Neuroimaging
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Head ultrasound
Head CT
Brain MRI
Neonatal Status Epilepticus
Treatment
• Etiology specific treatment if possible
– Hypoglycemia
• Correct with 10% glucose solution IV 2cc/kg
• Maintenance glucose infusion to max of 8 mg/kg/min
– Hypocalcemia
• Treat with 10% calcium gluconate (100 mg/kg or 1ml/kg IV
over 5-10 minutes while monitoring heart rate and infusion
site; or calcium chloride (20mg/kg or 0.2 ml/kg)
– Hypomagnesemia
• Often associated with hypocalcemia
• Treat with 50% solution of magnesium sulfate IM, 0.25 ml/kg
– Pyridoxine dependency
• Used empirically in infants with refractory seizures
• While EEG monitoring, give 100 mg/kg IV
Neonatal Status Epilepticus
Treatment
• Phenobarbital
– Usually used first
– Prolonged half life—100 hours after day 5-7; therefore watch for toxicity
– 20 mg/kg IV (up to 40 mg); repeat 10/kg every 15-30 minutes times two
• Phenytoin/Fosphenytoin
– 20 mg/kg (over 30-45 minutes)
– Half-life 100 hours
– Nonlinear kinetics; redistribution, variable rate hepatic metabolism
require individuallization of maintenance dosing
• Benzodiazepine
– Diazepam
• 0.25mg/kg IV bolus or 0.5 mg/kg PR
– Lorazepam
• 0.05 mg/kg IV over2-5 minutes
• Midazolam infusion
References
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Riviello JJ et al: Practice Parameter: Diagnostic assessment of the child with
status epilepticus (an evidence based review): Report of the Quality Standards
Subcommittee of the American Academy of Neurology and the Practice
Committee of the Child Neurology Society, Neurology 2006;67;1542-1550.
Appleton et al: Drug management for acute tonic-clonic convulsions including
convulsive status epilepticus in children, The Cochrane Collaboration, Volume
(4), 2006.
Fenichel GM: Clinical Pediatric Neurology: A Signs and Symptoms Approach, 5th
Edition, Elsevier Suanders 2005, p 1-45.
Mizrahi,EM and Kellaway p: Diagnosis and Management of Neonatal Seizures,
Lippincott-Raven, Philadelphia, 1998,p. 181.
Tharp, Barry: Management of Status Epilepticus in Children, Uptodateonlline.com
The Status Epilepticus Working Party: The treatment of convulsive status
epilepticus on children, Arch Dis Child 2000;83;415-419.
Wolfe et al: Intranasal midazolam therapy for pediatric status epilepticus,
American Journal of Emergency Medicine 2006; 24(3);343-346.