Dr. Ravindra K. SharmaPediatric Specialist

Status Epilepticus

“Status epilepticus is a medical emergency that requires an organized and skillful approach to minimize the associated mortality and morbidity”

• 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.

Definition:

• Conventional definition:

–Single seizure > 30 minutes

–Series of seizures > 30 minutes without full recovery

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

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

But

• This is not practical operational definition.• Longer periods with uncontrolled seizure

activity, more likely to develop a RSE syndrome.

• More practical guidelines needed to draw that arbitrary ‘line in sand’, beyond which substantial risk of developing clinical SE exists.

“Continuous seizures lasting at least 5 minutes or two or more discrete seizures between which

there is an incomplete recovery of consciousness”

Operational Definition:

Causes.

• Fever• Medication change• Unknown• Metabolic• Congenital• Anoxic• Other (trauma, vascular,

infection, tumor, drugs,endocrine)

36 %20 % 9 % 8 % 7 % 5 %15 %

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

Pathophysiology • GLUTAMATE = the major excitatory AA

neurotransmitter in brain– Any factor increases Glutamate activity can lead to

seizures– NMDA(N-methyl-D-aspartic acid) is an AA derivative

which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate

• GABA = main inhibitory neurotransmitter, ; GABA antagonists can cause SE

Drugs which can cause seizures

• Antibiotics– Penicillins– Isoniazid– Metronidazole

• Anesthetics, narcotics– Halothane, enflurane– Cocaine, fentanyl– Ketamine

• Psychopharmaceuticals– Antihistamines– Antidepressants– Antipsychotics– Phencyclidine– Tricyclic antidepressants– List of drugs

Mortality

• Adults• Children

15 to 22% 3 to 15%

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

Prolonged seizures

Duration of seizureDuration of seizure

Life Life threateningthreatening

systemicsystemicchangeschanges

DeathDeathTemporaryTemporary

systemicsystemicchangeschanges

Respiratory

• Hypoxia and hypercarbia

- ventilation (chest rigidity from muscle spasm)- Hypermetabolism ( O2 consumption, CO2 production)- Poor handling of secretions- Neurogenic pulmonary edema?

Hypoxia

• Hypoxia/anoxia markedly increase the risk of mortality in SE

• Seizures (without hypoxia) are much less dangerous than seizures and hypoxia

Towne AR. Epilepsia 1994;35(1):27-34

Neurogenic pulmonary edema

•Rare complication •Likely occurs as consequence of marked increase of pulmonary vascular pressure

Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32

Acidosis

• Respiratory• Lactic

– Impaired tissue oxygenation– Increased energy expenditure

Hemodynamics

• Sympathetic overdrive – Massive

catecholamine / autonomic discharge

– Hypertension– Tachycardia– High CVP

Exhaustion Hypotension Hypoperfusion

Exhaustion Hypotension Hypoperfusion

0 min0 min 60 min60 min

Cerebral blood flow - Cerebral O2 requirement

• HyperdynamicHyperdynamic phasephase – CBF meets CMROCBF meets CMRO22

• Exhaustion phaseExhaustion phase– CBF drops as CBF drops as

hypotension sets inhypotension sets in– Autoregulation Autoregulation

exhaustedexhausted– Neuronal damage ensues

• HyperdynamicHyperdynamic phasephase – CBF meets CMROCBF meets CMRO22

• Exhaustion phaseExhaustion phase– CBF drops as CBF drops as

hypotension sets inhypotension sets in– Autoregulation Autoregulation

exhaustedexhausted– Neuronal damage ensues

Blood pressure

Blood flow

O2 requirement

Seizure duration

Glucose

• Hyperdynamic phase – Hyperglycemia

• Exhaustion phase– Hypoglycemia

develops– Hypoglycemia appears

earlier in presence of hypoxia

– Neuronal damage ensues

• Hyperdynamic phase – Hyperglycemia

• Exhaustion phase– Hypoglycemia

develops– Hypoglycemia appears

earlier in presence of hypoxia

– Neuronal damage ensues

Glu

cose

Seizure duration

30 min

SE

SE + hypoxia

Hyperpyrexia

• Hyperpyrexia may develop during protracted SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery

• Treat hyperpyrexia aggressively–Antipyretics, external cooling

Other alterations

• Blood leukocytosis (50% of children)• Spinal fluid leukocytosis (15% of children)• K+

• creatine kinase• Myoglobinuria

Acute Management of Seizures

Oxygen, oral airway. Avoid hypoxia!

Consider bag-valve mask ventilation. Consider intubation

IV/IO access. Treat hypotension, but NOT hypertension

AA

BB

CC

Common Sense:0-5 minutesStabilize the patient-

(0-5 minutes)…

• Arterial blood gas?– All children in SE have acidosis. It often resolves rapidly

with termination of SE

• Intubate?– It may be difficult to intubate the actively seizing child– Stop or slow seizures first, give O2, consider BVM

ventilation– If using paralytic agent to intubate, assume that SE

continues

0-5 minutes….Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless

normo- or hyperglycemicHyperglycemia has no negative effect in SE

(as long as significant hyperosmolality is being avoided)

Adoloscent-Thiamin 100 mg IV first

Initial investigations(0-5 minutes)….

• Labs– Na,K, Ca, Mg, PO4 , BUN, Cret, glucose– CBC– Liver function tests, ammonia– Anticonvulsant level– Toxicology– Blood C/S

• Initial screening history and Physical examination

Work-Up (when stable)

• Lumbar puncture– Always defer LP in unstable patient, but never delay

antibiotic/antiviral rx if indicated

• CT scan/MRI scan– Indicated for focal seizures or deficit, history of trauma or

bleeding d/o

• EEG

Treatment (Pharmacotheraqpy)5-15 minutes..

• The longer we wait with anticonvulsant, the more anticonvulsant we will need to stop SE

• Most common mistake is ineffective dose

Anticonvulsants

• Rapid acting

plus

• Long acting

Anticonvulsants - Rapid acting

• Benzodiazepines– Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 4-

6 mg over 1-2 minutesor

– Diazepam 0.2- 0.5 mg/kg i.v. upto 6-10mg over 1-2 minutes

– Diazepam 0.5 mg/kg rectally– Midazolam 0.15-0.3 mg/kg IV ; nasal or Buccal (0.5

mg/kg) is used if no IV line– If SE persists, repeat every 5-10 minutes

Benzodiazepines

• Diazepam– High lipid solubility– Thus very rapid onset – Redistributes rapidly– Thus rapid loss of

anticonvulsant effect– Adverse effects are

persistent:• Hypotension• Resp. depression

• Lorazepam– Low lipid solubility– Action delayed 2 minutes– Anticonvulsant effect 6-12 hrs– Less respiratory depression than

diazepam

Midazolamfor brief seizures May be given i.m. to treat refractory SE

Anticonvulsants :15-35 minutes(If seizures persists)

• Phenytoin– 15-20 mg/kg i.v. over 15-20

min– pH 12

Extravasation causes severe tissue injury

– Onset 10-30 min– May cause hypotension,

dysrhythmia– Dilute with Dext. free solution– Cheap

• Fosphenytoin– 15-20 mg PE/kg i.v./i.m. over 5-

7 min PE = phenytoin equivalent

– Fosphenytoin 150 mg is equal to 100 mg phenytoin

– pH 8.6Extravasation well tolerated

– Onset 5-10 min– May cause hypotension– Expensive

Anticonvulsants :(15-35 minutes)

• Phenobarbital–15-20 mg/kg (neonate 20-30 mg/kg)i.v. over

15-20 min–Onset 15-30 min–May cause hypotension, respiratory

depression

Initial choice of long acting anticonvulsants in SE

Is patient an infant?Is patient already receiving phenytoin?

YesNo

At high risk for extravasation ?(small vein, difficult access etc.)?

Phenobarbital

YesYesNoNo

Phenytoin Fosphenytoin

Preffered in Cardiac patient, Head trauma,

If SE persists (45 minutes)

• Phenobarbital if Phenytoin used• Additional phenytoin or FP 5 mg/kg (Nelson 10 mg/kg

increment) max upto 30 mg ,• Additional phenobarbital 5 mg/kg/dose every 15–30

min (max total dose of 30 mg/kg) • be prepared to support respirations• Consider IV valproate, especially for partial status

epilepticus

Seizures Persists (60 minutes)

• Consider Diazepam infusion, pentobarbital (Barbiturate coma), midazolam, paraldehyde or general anesthesia infusion in PICU

• Midazolam 0.2 mg/kg bolus & 20-400 mcg/kg/hr infusion

• Propofol 1-2 mg/kg then 2-10 mg/kg/hr infusion

• Avoid paralytics

Still Seizures Persists….

• Induction of Barbiturate coma for 48 hrs• IV loading thiopental 2–4 mg/kg till a burst

suppression EEG pattern till 48 hrs • check phenobarbital level to be normal.

• Paraldehyde :loading 150–200 mg/kg IV for 15–20 min, then 20 mg/kg/hr in a 5% concentration in a glass bottle freshly prepared

Still Seizures Persists….

• General anesthesia: if barbiturate coma is not option.– halothane and Isoflurane. – Acts by reversing cerebral anoxia and metabolic

abnormalities, allowing the previously administered anticonvulsants to exert their effect.

Possible new drugs for Status

• Lidocaine - some positive trials• Valproate - IV form available

• 10-15 mg/kg IV. • Gabapentin / Vigabatrin / Lamotrigine• Felbamate - blocks NMDA receptors• Ketamine - blocks NMDA receptors

Use of AED after status episode is controversial especially idiopathic or febrile seizure.

Non - convulsive status epilepticus?

• NCSE is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in non convulsive clinical symptoms.

Non - convulsive SE ?

• Up to 20 % of children with SE have non - convulsive SE after tonic - clonic SE

Non - convulsive 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

Summary

• Status Epilepticus is >5 min of seizures or two seizures without return to consciousness

• Status Epilepticus is common• Delay in therapy makes SE harder to rest• Mortality and morbidity is increased in prolonged SE• BZD, Pheny/Pheno, Call for PICU• Status Epilepticus needs a DIAGNOSIS

Take-Home points -

• Better outcome if seizure stopped earlier, so no need to wait

• Always ABC D FIRST• Lorazepam - best 1st line Rx• Fosphenytoin - surpasses Phenytoin for SE, and can be

given IM in difficult situation• Propofol - advantages over barbiturates for resistant SE,

low toxicity , quick action, and fast recovery upon discontinuation