Generalized, Tonic-Clonic

Status Epilepticus in Children

Rizqi Rokhmadhoni P, SpA
SubDep IKA FK UHT/RSAL Dr. Ramelan -
Surabaya
• Status epilepticus (SE) presents in a multitude of
forms, dependent on etiology and patient age
(myoclonic, tonic, subtle, tonic-clonic, absence,
complex partial etc.)
• Generalized, tonic-clonic SE is the most common
form of SE
• The following presentation refers to generalized,
tonic-clonic SE

Status epilepticus 2
 Definition
• No consensus on exact definition
20-30 min : injury to CNS neurons
• Conventional definition:
– Single seizure > 30 minutes
– Series of seizures > 30 minutes without full recovery

Status epilepticus 3
 Definition
– “If appropriate therapy is delayed, SE can cause
permanent neurologic sequelae or death …”

thus

– “ … any child who presents actively convulsing should

be assumed to have SE.”
Haafiz A. Pediatr Emerg Care 1999;15(2):119-29

Status epilepticus 4
The longer SE persists,

–the lower is the likelihood of spontaneous cessation

–the harder is it to control
–the higher is the risk of morbidity and mortality

Treatment for most seizures needs to be instituted

after > 5 minutes of seizure activity
Bleck TP. Epilepsia 1999;40(1):S64-6

Status epilepticus 5
 Epidemiology - SE
• life threatening
• USA: -102,000 -152,000 cases / year -
52,000 deaths / year
• of new cases of epilepsy, 12 -30% present
in Status
• generalized Status is most common form -
and subject of this review

Status epilepticus 6
 Mortality
• Adults 15 to 22%
• Children 3 to 15%

Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30

Status epilepticus 7
 Pathophysiology - SE
• numerous mechanisms - poorly understood
– excess excitation or ineffective inhibition
– there are excitatory and inhibitory receptors in the brain -
activity is usually in balance

Status epilepticus 8
 Pathophysiology - SE
• GLUTAMATE = the major excitatory AA
neurotransmitter in brain
– any factor which increases Glutamate activity can lead to
seizures
– e.g. 1987- mussels contaminated with Domoic acid, a
glutamate analog --> profound SE / deaths

Status epilepticus 9
 Pathophysiology - SE
• GABA = main inhibitory neurotransmitter
– GABA antagonists can cause SE - eg Penicillins,
other antibiotics
– prolonged sz can desensitize GABA receptors

Status epilepticus 10
 Pathophysiology - SE
• CNS damage can occur - mechanism:
– uncontrolled neuronal firing -> excess glutamate -> this
sustained high influx of calcium ions into neurons
leads to cell death (“excitotoxicity”)
– GABA released to counteract this, but GABA receptors
eventually desensitize
– these effects worsened if hyperthermia, hypoxia, or
hypotension

Status epilepticus 11
 Pathophysiology - SE
• PHASE 1 (0-30 min) -- compensatory mechanisms
remain intact
– adrenaline or noradrenaline release ++
– increased CBF & metabolism
– hypertension, hyperpyrexia
– hyperventilation, tachycardia
– lactic acidosis

Status epilepticus 12
 Pathophysiology - SE
• PHASE 2 (>30 min) -- compensatory mechanisms
failing
– cerebral autoregulation fails / cerebral edema
– respiration depressed
– cardiac arrhythmias
– hypotension
– hypoglycemia, hyponatremia
– renal failure, rhabdomyolysis, hyperthermia
– DIC

Status epilepticus 13
 Physiological Changes in GTCSE-
Compensation

Cerebral changes Metabolic changes Autonomic changes

Increased blood flow Hyperglycemia Hypertension

Energy requirements Lactic acidosis Increased CO
are matched by Increased CVP
increased lactate, Massive
increased glucose
Catecholamines
Tachycardia
Arrythmias
Hyperpyrexia
Vomiting

Status epilepticus 14
 Physiological Changes in GTCSE-
Decompensation

Cerebral changes Metabolic changes Autonomic changes

Failure of Hypoglycemia Hypoxia

autoregulation Hyponatremia Decreased blood
Hypoxia Hypo/Hyperkalemia pressure
Hypoglycemia Acidosis Falling CO
Decreased lactate Hepatic/Renal Pulmonary edema
Increased ICP dysfunction CHF
Cerebral edema DIC Arrythmias
Rhabdomyolysis Hyperpyrexia
Serum/CSF
leukocytosis
Status epilepticus 15
Cerebral blood flow - Cerebral O2 requirement
• Hyperdynamic
phase
O2 requirement – CBF meets CMRO2
• Exhaustion phase
– CBF drops as
hypotension sets in
Blood flow
– Autoregulation
Blood pressure
exhausted
– Neuronal damage ensues

Seizure duration

Status epilepticus 16
 Glucose

• Hyperdynamic
phase
Glucose

– Hyperglycemia
• Exhaustion phase
SE
– Hypoglycemia develops
– Hypoglycemia appears
earlier in presence of
30 min hypoxia
SE + hypoxia
– Neuronal damage ensues
Seizure duration

Status epilepticus 17
Status epilepticus 18
Imaging Evidence of SE Damage

Status epilepticus 19
 Causes
• Fever 36%
• Medication change 20%
• Unknown 9%
• Metabolic 8%
• Congenital 7%
• Anoxic 5%
• Other (trauma, vascular, infection, 15%
tumor, drugs)

DeLorenzo RJ. Epilepsia 1992;33 Suppl 4:S15-25

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 Drugs which can cause seizures
• Antibiotics • Psychopharmaceuticals
– Penicillins – Antihistamines
– Isoniazid – Antidepressants
– Metronidazole – Antipsychotics
• Anesthetics, narcotics – Phencyclidine
– Halothane, enflurane – Tricyclic antidepressants
– Cocaine, fentanyl
– Ketamine

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 Prolonged seizures

Life
Temporary
threatening
systemic Death
systemic
changes
changes

Duration of seizure

Status epilepticus 22
 OUTLINE - Management of SE
• General approach & management
1. Maintenance of oxygenation and circulation
2. Assessment of etiology and lab evaluations
3. Obtaining intravenous access and initiation of therapy

• Anti - Epileptic Drugs:

– Benzodiazepines
– Phenytoin / Fosphenytoin
– Barbiturates
– Propofol
– others / new possibilities

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 General Measures in
SE Management
• Maintenance of oxygenation and circulation
(ABC’s : monitor / O2 / large IV’s)
- Metabolic Acidosis : give bicarbonat
- if intubating/ventilating : avoid muscle relaxan :
mask seizure activity

• Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%),

unless normo- or hyperglycemic
Hyperglycemia has no negative effect in SE
(as long as significant hyperosmolality is being avoided)

Status epilepticus 24
 Assessment of etiology and lab evaluations

• Labs
– Na, Ca, Mg, PO4 , glucose
– CBC
– Liver function tests, ammonia
– Anticonvulsant level
– Toxicology
• Lumbar puncture
– Always defer LP in unstable patient, but never delay
antibiotic/antiviral rx if indicated
• CT scan
– Indicated for focal seizures or deficit, history of trauma or
bleeding
Status epilepticus 25
 Obtaining intravenous access and initiation of
therapy
• Ideal Antiepileptic Drug
1. Intravenous routes
2. Few adverse effects
3. High CNS penetrance
4. Easy pharmacokinetics
5. Rapid efficacy : prompt onset, long-acting
6. No depression of cardio-resp function /mental
status

Status epilepticus 26
 AEDs for Status epilepticus
• Benzodiazepines
– Diazepam
– Lorazepam
– Midazolam
• Phenytoin ( Fosphenytoin)
• Valproic acid
• Phenobarbital

Status epilepticus 27
 Benzodiazepines
• Diazepam (Valium, Diastat)
• Lorazepam (Ativan)
• Midazolam (Versed)

Status epilepticus 28
 Benzodiazepines

• Lorazepam • Diazepam
– Low lipid solubility – High lipid solubility
– Action delayed 2 minutes – Thus very rapid onset
– Anticonvulsant effect 6-12 hrs – Redistributes rapidly
– Less respiratory depression than – Thus rapid loss of
diazepam anticonvulsant effect
– Adverse effects are
persistent:
• Midazolam • Hypotension
– May be given i.m. • Respir depression

Status epilepticus 29
 Lorazepam vs. Diazepam
Lorazepam Diazepam

 Duration of 12 -24 hr < 1 hr

action
 Onset of action 2-3 min 1-3 min
 Sedation + ++

Status epilepticus 30
 Anticonvulsants - Long acting
• Phenytoin • Fosphenytoin
– 20 mg/kg i.v. over 20 min – 20 mg PE/kg i.v. over 5-7 min
PE = phenytoin equivalent

– pH 8.6
– pH 12
Extravasation well tolerated
Extravasation causes severe
tissue injury – Onset 5-10 min
– Onset 10-30 min – May cause hypotension
– May cause hypotension,
dysrhythmia – Expensive
– Cheap

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 Anticonvulsants - Long acting
• Phenobarbital
– 20 mg/k g i.v. over 10 - 15 min
– Onset 15-30 min
– May cause hypotension, respiratory depression

Status epilepticus 32
 Drug Rx - Refractory SE
• Anesthetic doses of:
– Midazolam (0.2 mg/kg slow IV bolus) - ->continuous IV infusion @
.4 - 6.0 mcg/kg/min OR .1 - 2.0 mg/kg/hr
– Propofol (1-2 mg/kg)
– Barbiturates (Thiopental, Phenobarbital, Pentobarbital)
– Inhalational anesthetics (Isoflurane)
• General Anesthetic can suppress immune system --
>infection
• Bleck TP. Management approaches to prolonged seizures and status epilepticus. Epilepsia 1999;40(1):S64-6.

Status epilepticus 33
 Anticonvulsants - Rapid acting
• Benzodiazepines
– Lorazepam 0.1 mg/kg i.v. over 1-2 minutes
– Diazepam 0.2 mg/kg i.v. over 1-2 minutes

– If SE persists, repeat every 5-10 minutes

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 Non - convulsive SE ?
• How do you tell that patient’s seizures have stopped?
• Neurologic signs after termination of SE are common:
– Pupillary changes
– Abnormal tone, Babinski
– Posturing, clonus
– May be asymmetrical
• Up to 20% of children with SE have non - convulsive SE after
tonic - clonic SE
• If child does not begin to respond to painful stimuli within 20 -
30 minutes after tonic - clonic SE, suspect non - convulsive SE
– Urgent EEG

Status epilepticus 35
TERIMA KASIH

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