Status epilepticus is a medical emergency defined as continuous seizure activity lasting more than 30 minutes or recurrent seizures without regaining consciousness between seizures. It requires prompt treatment to prevent neurological injury and death. The document discusses the epidemiology, pathophysiology, treatment, and prognosis of status epilepticus. Initial treatment involves maintaining airway, breathing, and circulation while administering benzodiazepines like lorazepam or diazepam. For refractory cases, additional anticonvulsants like fosphenytoin, phenobarbital, midazolam, or propofol may be used. Outcomes depend on factors like duration and etiology of seizures, with mortality ranging from 3-30

1. STATUS EPILEPTICUS
Dr. Manoj Kumar Singh
Assistant Professor
PMCH Patna

2. Electrical power house

3. Status Epilepticus
An important Medical Emergency dealt by
Physicians
Pediatrician
Neurologists
Family physician
Prompt & efficient treatment
↓mortality & morbidity.
Regional differences in epidemiology

4. 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%

6. Frequency of seizure in different age
groups
0
5
10
15
20
Noofpatients
1st 2nd 3rd 4th 5th 6th >6th
Decades
frequency of status epilepticus in different age
group
Kalita J et al 2009

7. 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

8. 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.

9. 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.

10. “Continuous seizures lasting at least 5
minutes
or two or more discrete seizures between
which there is an incomplete recovery of
consciousness”
Operational Definition:

11. 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

12. 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.

13. 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%.

14. 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.

15. Causes of SE
63
15
7
9
13
Infection
Stroke
Metabolic
Drug default
Misc
Kalita J et al 2009

16. 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.

17. Prolonged seizures
Duration of seizureDuration of seizure
LifeLife
threateningthreatening
systemicsystemic
changeschanges
DeathDeath
TemporaryTemporary
systemicsystemic
changeschanges

18. Respiratory
• Hypoxia and hypercarbia
- ⇓ ventilation (chest rigidity from muscle
spasm)
- Hypermetabolism (⇑ O2 consumption, ⇑ CO2
production)
- Poor handling of secretions
- Neurogenic pulmonary edema?

19. 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

20. 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

21. Acidosis
• Respiratory
• Lactic
– Impaired tissue oxygenation
– Increased energy expenditure

22. Hemodynamics
• Sympathetic overdrive
– Massive
catecholamine /
autonomic discharge
– Hypertension
– Tachycardia
– High CVP
 Exhaustion
 Hypotension
 Hypoperfusion
0 min0 min 60 min60 min

23. Cerebral blood flow - Cerebral O2
requirement
• HyperdynamicHyperdynamic
phasephase
– CBF meets CMROCBF meets CMRO22
• ExhaustionExhaustion
phasephase
– CBF drops asCBF drops as
hypotension sets inhypotension sets in
– AutoregulationAutoregulation
exhaustedexhausted
– Neuronal damage
ensues
• HyperdynamicHyperdynamic
phasephase
– CBF meets CMROCBF meets CMRO22
• ExhaustionExhaustion
phasephase
– CBF drops asCBF drops as
hypotension sets inhypotension sets in
– AutoregulationAutoregulation
exhaustedexhausted
– Neuronal damage
ensues
Blood pressure
Blood flow
O2 requirement
Seizure duration

24. 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
Glucose
Seizure duration
30 min
SE
SE + hypoxia

25. Other alterations
• Blood leukocytosis (50% of children)
• Spinal fluid leukocytosis (15% of
children)
• ⇑ K+
• ⇑ creatine kinase
• Myoglobinuria

26. Management in the hospital
• Any patient who comes to emergency & is
convulsing requires aggressive treatment.
• Aim:
Maintain vitals
Termination of SE,s
Prevent seizure recurrence
Management of precipitating causes
Correct metabolic imbalance
Management of systemic complications

27. 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

28. 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.

31. 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
Midazolam
for brief seizures
May be given i.m.
 to treat refractory SE

32. 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 12
Extravasation causes
severe tissue injury
pH 8.6
Extravasation well
tolerated
• 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

33. 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.

34. 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.

35. Initial choice of long acting
anticonvulsants in SE
Is patient an infant?Is patient an infant?
Is patient already receivingIs patient already receiving
phenytoin?phenytoin?
Is patient an infant?Is patient an infant?
Is patient already receivingIs patient already receiving
phenytoin?phenytoin?
YesYesNoNo
At high risk forAt high risk for
extravasation ?extravasation ?
(small vein, difficult access etc.)?(small vein, difficult access etc.)?
PhenobarbitalPhenobarbital
YesYesNoNo
PhenytoinPhenytoin FosphenytoinFosphenytoin

36. 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

37. 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

38. 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

39. 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.

40. 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.

41. 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

42. 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

43. 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

44. Mortality & morbidity of GCSE
• Mortality:
– 3-30%
– Children< adults
• If GCSE last >30min
– Respiratory compromise→Hypoxia →Acidosis
– Hypoglycemia
Hypotension

45. 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

46. Mortality in SE (n=117)
Kalita J, Nair PP, Misra UK. J Neurol 2012

47. 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

48. Thank You & Good Luck