Status Epilepticus in Children. Definitions Status Epilepticus: 30 minute duration of seizures (or two or more sequential seizures without full recovery.

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

• Hypoxemia• Acidemia• Glucose alterations• Blood pressure disturbances• Increased intracranial pressure• Morbidity

– Neurologic sequelae– Focal motor deficits– Mental retardation– Behavioral disorders– Chronic epilepsy– Acute and chronic MRI changes

• Mortality– 3-4%

Assessment of the Patient with Status Epilpeticus

1. Determine if patient is having a seizure

2. Determine type of seizure

3. Determine possible etiology of seizure

4. Treat underlying etiology of seizure if pertinent

5. Stop the seizure

Differential DiagnosisIs 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• loss of consciousness

• whole brain at onset

Partial• no loss of consciousness

• focal onset

Convulsive• tonic clonic

• tonic

• clonic

Nonconvulsive • absence

• atypical absence

• myoclonic

• atonic

Complex Partial• change in level of consciousness

Simple Partial• no change in consciousness

Partial Seizure evolving to secondary generalization

Etiology of Status Epilepticus

• 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 Epilepticusin Children--Initial Approach

Status Epilepticus Working Party, 2000 (mostly)• Initial assessment

– 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– Glucose, electrolytes, calcium, magnesium– ABG– CBC– Serum anticonvulsant drug levels (if indicated)– Toxicology screening

Rapid Neurologic Evaluation• Observation

– What is the patient doing• 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

• 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 Epilepticusin Children--Initial Approach

• Initial assessment– 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– Glucose, electrolytes, calcium, magnesium– ABG– CBC– Serum anticonvulsant drug levels (if indicated)– Toxicology screening

Copyright ©2000 BMJ Publishing Group Ltd.

The Status Epilepticus Working Party, et al. Arch Dis Child 2000;83:415-419

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Management of Status Epilepticusin 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– 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 ChildStep 2

• ADD fosphenytoin:20 PE/kg over 7 min.– 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

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

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 ChildStep 3

• ADD third medication if necessary– Phenobarbital 20mg/kg IV (2 mg/kg/min)\

• 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

• Inhalational anesthetics• Pentobarbital

• 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• Propofol

• Intravenous anesthetic; Risk of hypotension, apnea and bradycardia• Contraindicated in child on ketogenic diet

• Midazolam• 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• Valproic acid

• 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

• Keppra• Consider IV pyridoxine

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 assessmentRiveillo 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 EpilepticusEtiology

• Hypoxic ischemic encephalopathy• CNS infection• Intracranial Hemorrhage• Cerebral Infarction• Chromosomal abnormalities• Congenital Brain abnormalities• Metabolic Distubances

– 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.

• 24 hours1. Meningitis/Sepsis2. Direct drug effect3. Hypoxic-ischemic encephalopathy4. Intrauterine infection5. Laceration of tentorium or falx6. Pyridoxine dependency7. Subarachnoid hemorrhage

• 24-72 hours1. Meningitis/sepsis2. Drug withdrawal3. Cerebral contusion/SDH4. Cerebral dysgenesis5. IVH in newborns6. Pyridoxine dependency7. Subarachnoid hemorrhage8. Urea cycle abnormalities9. Hypoparathyroidsm-hypocalcemia

• 72 hours – 1 week1. Familial neonatal seizures2. Cerebral dysgenesis3. Cerebral infarction4. Hypoparathyroidism5. Intracerebral hemorrhage6. Kernicterus7. Nutritional hypocalcemia8. Methylmalonic/ propionic acidemia9. Urea cycle abnormalities

• 1 week- 4 weeks1. Neonatal adrenoleukodystrophy2. Cerebral dysgenesis3. Fructose dysmetabolism4. Gaucher Type 25. Gm1 gangliosidosis6. Herpes simplex encephalitis7. MSUD8. Urea cycle abnormalities

Diagnostic Assessment of Neonatal Seizures

• Metabolic testing (screening)– Blood glucose– Calcium– Ammonia– Lactate– pH– electrolytes

• LP– Cells– Protein/glucose– Cultures– Herpes PCR– Lactate/pyruvate– Aminoacids

• Neuroimaging– Head ultrasound– Head CT– Brain MRI

Neonatal Status EpilepticusTreatment

• 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 EpilepticusTreatment

• 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

• 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, 5 th 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.