Status epilepticus (SE) is a medical emergency defined by continuous seizure activity lasting more than 5 minutes for generalized seizures or more than 10 minutes for focal seizures. The condition requires rapid treatment to prevent neuronal injury and death from prolonged excitatory activity. Management involves initial airway and hemodynamic stabilization, followed by benzodiazepines as first-line treatment. If seizures continue, second-line drugs like phenytoin are used. Refractory SE fails to respond to first- and second-line drugs, while super-refractory SE continues despite anesthesia with midazolam or barbiturates. Early, aggressive treatment is needed to terminate seizures and prevent neurological complications.

1. STATUS EPILEPTICUS
Dr. Kumar keshav chandra
JR 3, Dept of Pediatrics

2. • Status epilepticus (SE) is a medical
emergency that should be anticipated in any
patient who presents with an acute seizure.
• The ILAE has refined the definition of SE to
reflect the time at which treatment should be
initiated (t1 ) and time at which continuous
seizure activity leads to long-term sequelae
(t2 ) such as neuronal injury.

3. • Classic old definition was seizure lasting more
than 30min or 2 or more seizure in this
duration without regaining consciousness in
between.
• This definition was based based on animal
studies that showed evidence of neuronal
damage after this time point, but this has
been reduced to emphasize the risks involved
with the longer durations and the need for
early and aggressive pharmacologic
intervention

4. • For generalized tonic-clonic seizures, SE is defined as
continuous convulsive activity or recurrent
generalized convulsive seizure activity without
regaining of consciousness (t1=5min, t2 ≥ 30 min).
• The definition differs for SE consisting of focal
seizures with impaired awareness (t1 = 10 min, t2 =
30 min) and absence SE (t1 = 10-15 min, t2 = unknown).

5. Time after which if seizure
don’t terminate , pt
considered in SE (t1)
Time after which ongoing
seizure have long term
consequences (t2)
Convulsive SE 5 min 30 min
Focal SE with impaired
consciousness
10 min >60 min
Absence SE 10-15 min unknown

6. • Operational definition of SE limited to 5min
because most seizures will terminate within
2min and if it persists beyond 5min its unlikely
terminate and more damage to the brain.
• more practically any patient who presents to
health care facility in convulsing state should
be assumed to be in SE.

7. Convulsive SE:- MC type of SE.
-manifests as generalized tonic, clonic, or tonic-clonic
Non convulsive SE:-
focal SE with impaired consciousness
Absence SE
Manifests as -confusional state, dementia,
- hyperactivity with behavioral problems,
- fluctuating impairment of consciousness,
-with at times unsteady sitting or walking,
-fluctuating mental status, hallucinations,
paranoia, aggressiveness catatonia, and or
psychotic symptoms.
It should be considered in any of these situations, especially in an
unresponsive or encephalopathic child.

8. • Refractory SE :-is SE that has failed to respond to
therapy, usually with at least two medications (such
as a benzodiazepine and another 2nd line medications
such as phenytoin, levetiracetam, valproic acid).
• Superrefractory SE ;- is SE that has failed to resolve,
or recurs, within 24 hr or more despite therapy that
includes a continuous infusion such as midazolam
and/or pentobarbital.

9. • New-onset refractory status epilepticus
(NORSE) has been identified as a distinct entity that
can be caused by almost any of the causes of SE in a
patientwithout prior epilepsy.
• It also is often of unknown etiology, presumed to be
encephalitic or postencephalitic, can last several
weeks or longer, and often, has a poor prognosis.

10. • Devastating epileptic encephalopathy in
school-age children (DESC), also called fever-
induced refractory epilepticencephalopathy
in school age children (FIRES), :-
• is a syndrome of refractory SE that is
associated with acute febrile infections,
appears to be parainfectious in nature
• appears to be highly drug resistant
• often responsive to the ketogenic diet.

11. • The incidence of SE ranges between 10 and 60 per 100,000
population.
• SE is most common in children younger than 5 yr of age, with an
incidence in this age-group of > 100 per 100,000 children.
• Approximately 30% of patients presenting with SE are having their
first seizure, and approximately 40% of these later develop epilepsy.
• Febrile status epilepticus is the most common type of SE in children
• In the 1950s and 1960s, mortality rates of 6–18% were reported
after SE.
• Currently, with the recognition of SE as a medical emergency, a
lower mortality rate of 4–5% is observed, most of it secondary to
the underlying etiology rather than to the seizures.
• SE carries an approximately 14% risk of new neurologic deficits,
most of them (12.5%) secondary to the underlying pathology

12. Etiology
• New-onset epilepsy of any type
• Febrile SE
• Drug intoxication (TCA) in children and drug and alcohol
abuse in adolescents; drug withdrawal or overdose in
patients taking AEDs
• Hypoglycemia; Hypocalcemia; Hyponatremia;
Hypomagnesemia;
• Acute head trauma; encephalitis; meningitis; autoimmune
encephalitis
• Ischemic (arterial or venous) stroke
• Intracranial hemorrhage
• Folinic acid and pyridoxine and pyridoxal-phosphate
dependency (these usually present in infancy, but
childhood onset is also possible.

13. • Inborn errors of metabolism such as nonketotic hyperglycinemia in
neonates and mitochondrial encephalopathy with lactic acidosis
(MELAS) in infants, children and adolescents; ion channel–related
epilepsies (e.g., sodium and potassium channel mutations)
• Hypoxic-ischemic injury (e.g., after cardiac arrest),
• Systemic conditions (such as hypertensive encephalopathy,
posterior reversible encephalopathy, renal or hepatic
encephalopathy);
• brain tumors; brain malformations, neurodegenerative disorders.
• Infections that are more likely to cause encephalitis with SE, such
as - herpes simplex (complex partial and convulsive status),
• -Bartonella (particularly nonconvulsive status),
-Epstein-Barr virus, and
-mycoplasma (postinfectious encephalomyelitis with any type
of status epilepticus).
• Postinfectious encephalitis and acute disseminated
encephalomyelitis are common causes of SE, including refractory
SE.

14. PATHOPHYSIOLOGY
• failure of desensitization of AMPA glutamate receptors, thus
causing the persistence of increased excitability,
• Reduction of GABA-mediated inhibition as a result of
intracellular internalization of GABAA receptors.
• This explains the clinical observation that SE is often less likely to
stop in the next specific period of time the longer the seizure
has lasted and why benzodiazepines appear to be decreasingly
effective the longer seizure activity lasts.
• During SE, there is an increased cerebral metabolic rate and a
compensatory increase in cerebral blood flow that, after
approximately 30 min, is not able to keep up with the increases
in cerebral metabolic rate. This leads to a transition from
adequate to inadequate cerebral oxygen tensions and, together
with other factors, contributes to neuronal injury resulting from
SE. AMPA( alpha amino 3-hydroxy 5-methyl lisoxazole 4-proproinate)

15. • CNS damage -----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

16. Clinical presentation
• MC is convusing SE.
During initial compensatory phase-sympathetic
overdrive leading to-
- increased C.O
-increased BP
-increased RBS
-increased blood lactate levels

17. Decompensation –homeostatic failure
Reduced C.O/ BS/SPO2 levels leading to
1. Cardiorespiratory collapse
2. Electrolyte imbalance
3. Rhabdomyolysis - Renal tubular
necrosis
4.Hyperthermia
5.Raised ICP & cerebral edema

18. Important to obtain a brief history
• It is important to obtain a brief history including
any history of seizure disorder, other symptoms
(fever), medication usage and allergies to
medications.
• This can be completed by a designated person not
immediately involved in the acute resuscitation.
• This history will allow a simultaneous search for
cause and focused physical examination to be
completed while termination of the seizure is
undertaken.

19. MANAGEMENT
• Broadly divided into :-
1)Initial stabilization
2)Seizure termination
3)Evaluation and Treatment of underlying
cause
Both diagnostic evaluation and seizure control
should be achieved simultaneously to improve
the outcome.

20. Initial Stabilization:
Airway: airway patency is maintained, 100% O2 should be provided to prevent
hypoxia
Breathing: in case of respiratory failure if GCS score is less than 8, rapid
sequence intubation must be done.
Circulation: IV access should be secured promptly. In case IV access is not easily
accessible buccal, rectal or intraosseus route can be considered
Vital parameters like Heart rate ,Respiratory rate,ECG and Oxygenation saturation
should be monitored

21. Seizure termination
Pharmacotherapy:-
• Mechanisms of action of AEDs, which are diverse, mainly involving
modulation of voltage-activated ion channels, potentiation of GABA, and
inhibition of glutamate.
1. Benzodiazepines:- these are 1st line drug for SE using either i/v
lorazepam, i/v diazepam, or i/m midazolam.
• BZD act at the GABA receptor and inhibit neuronal transmission.
• However, as seizures progress, these receptors are internalized resulting
in lesser efficacy of these drugs in prolonged seizures. The potency of
benzodiazepines may decrease 20-fold in 30 min of SE.
• If intravenous access is not available, other options besides i/m
midazolam include buccal or intranasal midazolam, intranasal lorazepam,
or rectal diazepam.
• With all options, respiratory depression is a potential side effect for which
the patient should be monitored and managed as needed. If seizures
persist 5 min after the initial benzodiazepine dose, a second dose of the
drug should be given.

22. • 2. PHENYTOIN:- Phenytoin, as a second line
agent, is usually indicated when seizure is not
controlled after one or more doses of
benzodiazepines. Phenytoin acts by slowing the
rate of recovery of voltage-activated sodium
channel.
• Infused at a L.D of 20mg/kg(not compatible with
dextrose solution) and infused @ 1mg/kg/min.
• phosphenytion – water soluble phosphate ester
of phenytoin and a prodrug of phenytoin.
• Lesser side effect as compared to phenytoin.
• 75 mg of phosphenytoin is equivalent to 50 mg of
phenytoin.

23. 3. Phenobarb :- acts by enhancing GABAa activity.
Used at a L.D of 20 mg/kg and infused @2mg/kg/min
has high incidence of resp depression , especiallu when used in addition
to BZDs.
4. Valproate:- acts It acts through several mechanisms of action including
modulation of sodium and calcium currents, and increasing inhibitory
GABA transmission. It has especially low risk of hemodynamic adverse
effects even at very high infusion rates. Variable doses ranging from 20 to
40 mg/kg over 5-10 min have been used with success.
• 5. Levetiracetam :- It is a new broad spectrum anticonvulsant. It is
minimally protein bound and excreted via renal route, hence requiring
dosage modification in renal dysfunction. It is free of any significant drug
interactions. It has multiple sites of action including calcium channels
glutamate receptors and GABA modulation. Also having Neuroprotective
effects.
• L.D @20-60 mg/kg at 5 mg/kg/min..

24. 6.Pyridoxine:- Pyridoxine-dependent seizures occur
due to a rare AR mutation in the ALDHTA1 gene
which encodes antiquitin.
This condition usually presents in the early infantile
period with seizures that are refractory to standard
anticonvulsants.
Intravenous pyridoxine 100mg trial should be
considered in children< 2 age with refractory SE.

25. 7.Midazolam Infusion:- Midazolam is effective not only as a
bolus dose in the ínitial management of SE but also later in
SE or refractory SE when second line drugs have failed.
- Midazolam is a water soluble benzodiazepine that is
rapidly acting, and has a short half life. It is metabolized in
the liver and excreted by the kidneys.
- Midazolam has been used upto(32 ug/kg/min with no
serious side effects.
- While rapid escalation of infusion rate after a bolus dose
may be associated with rapid seizure control, there would
be a concern about early need for intubation and
mechanical ventilation.

31. Management of refractory SE
I V Mdazolam 0.2 mg/kg bolus followed by infusion @ 1 mcg/kg/min
increasing to 1 mcg/kg/min every 5-10 min till seizure stop, upto a
maximum of 30 mcg/kg/min.
• Starts tapering 24 hr after seizure stops@ 1 mcg/kg/min.
• Because most of these patients need to be intubated and paralyzed,
the EEG becomes the method of choice by which to follow them.
• If seizure persists on midazolam infusion
• Barbiturate coma( Thiopentol and Pentobarbitol);- these are
barbiturate anaesthetic, and have good efficacy in RSE but having
serious side effect.
• Pentobarbitol is not available in India.

32. • Thiopental has been used in a loading dose of 3-5
mg/kg followed by further boluses of 1-2 mg/kg
within 3-5 min till seizure stop( max dose of
10mg/kg) followed by a continuous infusion of 3-
5 mg/kg/hr.
• Starts tapering after 24 hr of seizure free period.
• Barbiturate coma is associated with serious side-
effects including hypotension, respiratory
depression and decreased cardiac contractility.
• These drugs may also cause suppression of
lymphocyte activation which is a cause of
concern in critically ill patients.

33. • Propofol :- t is an intravenous general anesthetic,
and acts through GABA receptors.
• Propofol can cause"propofol infusion syndrome
in children with higher infusion rates (>67
μg/kg/min), characterized by cardiac failure,
rhabdomyolysis, metabolic acidosis, renal failure,
and sometimes death.
• This limits the use of propofol in the pediatric
population
• Propofol is used as an initial bolus of 1-2 mg/kg,
followed by a continuous infusion of 1-2 mg/kg/h
and titrated to amaximum of 5 mg/kg/h.
• Limit use to <48 hr.

34. • Ketamine;- It is a non-competitive NMDA receptor
antagonist, and may also have additional
neuroprotective effects.
• It is administered iv with initial bolus of 1.5 mg/kg
followed by an infusion @ of 0.01-0.05 mg/kg/h.
• However, ketamine may increase ICP and hence,
should be used only after neuroimaging has ruled
out Space occupying lesion.
• Starts tapering after 24 hr of seizure free period.

35. superrefractory SE
• Patients with superrefractory SE have persistent seizure activity or
seizure recurrence despite 24 hr of general anesthesia with
medications such as midazolam, pentobarbital, and/or propofol.
• In addition to these continuous infusions, polytherapy with other
AEDs is usually initiated, most commonly used drugs are
fosphenytoin, valproate, phenobarbital, levetiracetam, topiramate,
and lacosamide.
• It differentiates from refractory status epilepticus (RSE) by the
failure of SE to resolve with anesthesia.
• Around 15% of all those presenting to the hospital in SE, develop
Super-refractory status epilepticus and the mortality is 30-50%.

36. • Others measure used in SRSE:-
• Ketogenic diet has also been found to be effective in patients with FIRES,
focal seizures and autoimmune encephalitis.
• Immunotherapy with IV steroids, immunoglobulins, and/or plasma
exchange is often used in cases of SRSE of unclear etiology.
In specific situations such as anti-NMDA receptor encephalitis or
CNS vasculitis immunotherapy may be the first-line therapy.
• Inhaled anesthetics such as isoflurane have been used for SRSE but are
associated with a number of adverse reactions.
• Induced hypothermia has also been used but further studies are needed
to assess its safety and efficacy.
• The use of vagal nerve stimulation, electroconvulsive therapy, and
transcranial magnetic stimulation has also been reported
• emergent neurosurgery such as hemispherectomy for Rasmussen
encephalitis or focal resection if the seizures are secondary to an area of
cortical dysplasia.
• Allopregnanolone, a neurosteroid, has shown promise in the treatment of
pediatric and adult SRSE, and clinical trials are currently underway to
better determine its efficacy

38. TAKE HOME MESSAGES:
1. Status Epilepticus is a life threatening medical emergency
that requires prompt recognition and management.
2. Attention to airway,breathing and circulation simultaneously
while treating seizure.
3. Early Rx aborts SE faster and prevents neuronal damage.
4. Initial management should consist of parenteral
benzodiazepines ; any agent by any route may be used
depending upon the availability and urgency.
5. Aggressive therapy is required for management of SE as
prolonged seizures are less responsive to therapy.