STATUS EPILEPTICUS

Dr. Manoj Kumar SinghAssistant Professor

PMCH Patna

Electrical power house

Status Epilepticus

An important Medical Emergency dealt by PhysiciansPediatrician NeurologistsFamily physician

Prompt & efficient treatment

↓mortality & morbidity.

Regional differences in epidemiology

Epidemiology

• USA 102000-152000/yr

• Highest (>50% of cases <3y) in children & >60yrs ,bimodal distribution

• Burden of SE in India 2,80,000/y

• Mortality • Adults

• Children

15 to 22%

3 to 15%

Frequency of seizure in different age groups

0

5

10

15

20

No

of

pat

ien

ts

1st 2nd 3rd 4th 5th 6th >6th

Decades

frequency of status epilepticus in different age group

Kalita J et al 2009

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

Definition of SE :

• Definition by ILAE in 1981 :

– Seizure lasting > 30 minutes

OR

Recurrent seizures > 30 minutes during which the pt. does not regain consciousness.

Why 30 minutes ?

Animal experiments in the 1970s and 1980s had shown that ...

… neuronal injury could be demonstrated after 30 min of seizure activity, even while maintaining respiration and circulation 1985;18(3):281-90.

“Continuous seizures lasting at least 5 minutes

or two or more discrete seizures between which there is an incomplete recovery of

consciousness”

Operational Definition:

Status epilepticus 11

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

TERMINOLOGY:

• CONVULSIVE SE : characterised by prolonged tonic clonic muscle contractions, associated loss of consciousness.

• Prolonged convulsive status epilepticus can degenerate into a non convulsive state look for subtle mouth twitching, eye movements etc.

• NON-CONVULSIVE SE – absence of overt muscle activity

• has continuous or near-continuous generalized electrical seizure activity for at least 30 minutes without physical convulsions.

• Diagnosis can be difficult - physical signs: agitation or confusion, nystagmus, or bizarre behaviors such as lip smacking or picking at items in the air.

TERMINOLOGY:

• NCSE is categorized into absence or complex partial SE based on EEG criteria.

• Absence SE - benign form of SE that does not cause serious brain damage.

• Complex partial SE is associated with neuronal injury and high morbidity and mortality ~ 3 times higher.

• aggressive treatment advocated.

REFRACTORY SE: When seizure have persisted for >60 minutes and have not responded to use of 3 or more medications. Mortality 16-32%.

ETIOLOGY:

• New onset epilepsy of any type.• Drug intoxication (eg. TCA’s), drug withdrawl and

abuse.• Electrolyte imbalance,• Acute head trauma.• Encephalitis, Meningitis,Stroke.• HIE, Brain tumors.• IEM• Neurodegenerative diseases.

Causes of SE

6315

79

13Infection

Stroke

Metabolic

Drug default

Misc

Kalita J et al 2009

ETIOLOGICAL CLASSIFICATION OF SE:

• CRYPTOGENIC: SE in absence of an acute precipitating CNS insult or metabolic dysfunction in a patient without a pre-existing neurologic abnormality.

• REMOTE SYMPTOMATIC: SE in a patient with a known history of a neurologic insult asociated with an increased risk of seizures(Stroke,TBI,static encephalopathy).

• FEBRILE: THE MOST COMMON TYPE IN CHILDREN. SE provoked solely by fever in a patient without a history of afebrile seizures.

• ACUTE SYMPTOMATIC: SE during an acute illness involving a known neurologic insult or metabolic dysfunction.

• PROGRESSIVE ENCEPHALOPATHY: SE in a pt. with a progressive neurologic disease.

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):428-32

Acidosis

• Respiratory

• Lactic– Impaired tissue oxygenation– Increased energy expenditure

Hemodynamics

• Sympathetic overdrive – Massive

catecholamine / autonomic discharge

– Hypertension– Tachycardia– High CVP

Exhaustion Hypotension Hypoperfusion

0 min0 min 60 min60 min

Cerebral blood flow - Cerebral O2 requirement

• HyperdynamicHyperdynamic phasephase – CBF meets CMROCBF meets CMRO22

• Exhaustion Exhaustion phasephase– 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 Exhaustion phasephase– 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

Other alterations

• Blood leukocytosis (50% of children)

• Spinal fluid leukocytosis (15% of children)

• ⇑ K+

• ⇑ creatine kinase• Myoglobinuria

Management in the hospital

• Any patient who comes to emergency & is convulsing requires aggressive treatment.

• Aim: Maintain vitalsTermination of SE,sPrevent seizure recurrenceManagement of precipitating causesCorrect metabolic imbalanceManagement of systemic complications

Immediate general care

• Airway: Suction, avoid mandible & tongue fall• Administer 02 by nasal catheter• IV access:

– blood sugar, electrolyte, LFT, KFT, AED level, coagulation level

– Administer 2-4ml/kg 10% dextrose if hypoglycemia.• Monitor BP: Immediate ↑BP, after 2 hr ↓BP• Fluid: Avoid over hydration but maintain

euvolemia.• Acidosis: Subsides with control of SE

HCO3 therapy unnecessary• Pyrexia: Cold sponging

Status epilepticus 28

Other investigations

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

antibiotic/antiviral rx if indicated

• Neuroimaging – Do if doubt of intracranial pathology,raised ICT,

history of trauma or presence of lateralising sign. If etiology is uknown (only after SE is controlled and

Pt. is stabilised) .MRI is more sensitive than CT.

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

Phenytoin Fosphenytoin

• 15-20 mg/kg i.v. @50mg/min• 100 mg phenytoin =

• 20 mg PE/kg i.v @ 150mg/min Fosphenytoin 150 mg

pH 12Extravasation causessevere tissue injury

pH 8.6Extravasation welltolerated

• Onset 10-30 min • Onset 5-10 min

•May cause hypotension, dysrhythmia(may be because of rapid administration and propylene glycol which is used as diluent)

• less cardiac complications as it is water soluble and propylene glycol is not used as diluent.

• Cheap • Expensive

Anticonvulsants - Long acting

PHENOBARBITONE:• First line agent in neonatal seizures.• A potent AED, acts by enhancing GABA-A

activity.• Dose- 20 mg/kg infused at no more than 30

mg/min.• Unacceptably high incidence of sedation and

respiratory depression and it may be difficult to perform neurological assesment upto 24-36 hrs.

Anticonvulsants - Long acting

LEVETIRACETAM:• New broad spectrum anticonvulsant, recently

been used with success in acute seizures and SE.

• Renal excretion, free from any significant drug interactions, neuroprotective effects demonstrated.

• Multiple sites of action- Ca, glutamate receptors and GABA modulation.

• LD- 30-60 mg/kg @ 5 mg/kg/min.

Initial choice of long acting anticonvulsants in SE

Is patient an infant?Is patient an infant?Is patient already receiving Is patient already receiving

phenytoin?phenytoin?

Is patient an infant?Is patient an infant?Is patient already receiving Is patient already receiving

phenytoin?phenytoin?

YesYesNoNo

At high risk for At high risk for extravasation ?extravasation ?

(small vein, difficult access etc.)?(small vein, difficult access etc.)?

PhenobarbitalPhenobarbital

YesYesNoNo

PhenytoinPhenytoin FosphenytoinFosphenytoin

Refractory SE

SE persisted for >60 min & have not respond to use of 3 or more drugs.

• Drugs: – Midazolam, thiopental, diazepam drip or

propofol drip, pentobarbital.

• Regular medication in optimal dose

• Tertiary care centre should be consulted

Drugs for management of Refractory SE

Drugs Initial IV dose(mg/kg)

Maintenance infusion

Remarks

Pentobarbital 5-15 1-5 mg/kg/hr Tritrate drip to seizure controll.

Propofol 1-3 2-10 mg/kg/hr Rapid infusion cause hypotension.

Midazolam 0.05-0.2 1-18 micro g/kg/min Less hemodynamic S/E.

Diazepam 0.1-0.3 0.1-1 mg/kg/hr Cardiorespiratory monitoring

Lignocaine 1-2 3-5 mg/kg/hr Proconvulsant at higher doses

Refractory SE

• Recent meta-analysis showed midazolam infusion is good choice for initial T/t of REF SE. Fewer hemodyanamic consequences and lesser need for invasive monitoring and mechanical ventilation.

• Propofol less effective than barbiturate• Propofol ↑mortality than midazolam

– Gilbert et al 1999; Niemeijer et al 2003

Emerging Therapies

• Inhalational Anaesthetic agents (isoflurane & desflurane)

Attractive features include efficacy, rapid onset of action, ability to titrate according to EEG.

Both drugs in end tidal concentrations of 1.2-5%achieved an EEG burst suppression and termination of seizure activity within minutes.

However further studies are needed in this field.

KETAMINE - An NMDA receptor antagonist

• Experimental studies have demonstrated synergistic action of diazepam and ketamine in termination SE.

• Efficacy in extremely refractory SE has been documented in both children and adults.

• No cardiac depressant properties, hence does not cause hypotension.

• Caution in patients with increased ICP. Ketamine increases ICP. Rule out SOL.

Treatment at home or PHC

• Seizure >5min or 3 seizures in 1hr

• Rectal diazepam 0.2-0.5mg/kg– Children: Onset→2nd dose 4hrs later– Adults: Onset →4 →12hrs

• No respiratory suppression

• ↓Seizure recurrence & ↑Global outcome

Pre-hospital treatment of SE

• Midazolam :– Buccal (Lancet, Scott et al 1999)– intranasal (BMJ,Lahat et al 2000)– IM (Emerg Med,Towne et al 1999)

• Paraldehyde PR 0.3-0.5mg/kg

NONPHARMACOLOGICAL TREATMENTS

• Resective surgery• Vagal nerve stimulation• KETOGENIC DIET- Diet high in fat and low in

carbohydrates. Induces ketosis in body and thought to suppress seizures by release of Leptin.Exact mechanism remains unknown.

• Hypothermia- decrease brain metabolism which is neuroprotective.

• Electroconvulsive therapy - ECT-dose-1 session daily for 3-8 days. Mechanism-not known

Mortality & morbidity of GCSE

• Mortality: – 3-30%– Children< adults

• If GCSE last >30min– Respiratory compromise→Hypoxia →Acidosis – Hypoglycemia

Hypotension

Prognosis of SE

• Type: GCSE worse than Partial complex partial & NCSE

• Etiology: Anoxia, encephalitis, stroke worse than drug default SE• Duration: >1hr has worse than shorter

duration of SE • Recurrence: Neurological deficit

Mortality in SE (n=117)

Kalita J, Nair PP, Misra UK. J Neurol 2012

Conclusion• GCSE >5 min should be considered for operational

def of SE• ABC, general care, fluid, electrolyte & nursing • Urgent pre hospital Rx by rectal Diazepam, nasal,

buccal or im Midazolam ?• Hospital Rx: lorazepam, Fosphenytoin, PB,

midazolam, propofol, VPA, inhalation anesthetics• EEG monitoring not a must• ICU care ideal but don’t leave the patients in

absence of ventilator

Thank You & Good Luck