Definition of status

epilepticus
Previous definition:
Convulsive status epilepticus has been defined as continuous
seizure activity lasting more than 30 min OR 2 or more seizures
in this duration without gaining consciousness between them

Recommendation of working group of Epilepsy

foundation of America .JAMA.1993

•Currently valid for research and epidemiological purposes only

•The operational definition has brought the time down to 5 min
•Any patient who presents to the health care facility in a
convulsing
state should be assumed to be in status epilepticus

Trinka et al .Epilepsia.201
Brophy et al.Neurocrit care.201
 Updated ILAE definition of
status epilepticus
t1 t2
Convulsive 5 min 30 min
status
epilepticus
Focal status 10-15 min >60 min
epilepticus with
impaired
consciousness
Absence status 10 min Unknown
epilepticus

t1=Time after which if seizures do t2=Time after which ongoing

not terminate, patient is considered seizures have long term
to be in status epilepticus Consequences

Trinka et al .Epilepsia.2015
Brophy et al.Neurocrit care.2012
 Updated ILAE definition of status
epilepticus
Established Status epilepticus that persists after treatment with
status a benzodiazepine (1st line treatment)
epilepticus

Refractory Status epilepticus that persists after the 1st line

status agent (benzodiazepine) and 2nd line agents
epilepticus (additional agents such as levetiracetam, phenytoin,
valproic acid)

Super Status epilepticus continuing for at least 24 hour

refractory after initiation of general anesthetic medications,
status including cases in which SE recurs with reduction of
epilepticus anesthesia

Trinka et al .Epilepsia.2015
 First line antiepileptic drug
Initial(1st line therapy) for SE Level of recommendation(AES
guidelines)
IV lorazepam and IV Level A
diazepam(equally efficacious)
IM midazolam Level B
Intranasal or buccal midazolam, Level B
PR diazepam
Intranasal /buccal midazolam Level B
superior to PR diazepam
Intranasal/sublingual/PR Level C
lorazepam, valproate,
levetiracetam, phenytoin
Phenobarbitone although has level A evidence as initial therapy, but
due to its slower rate of administration, BZD is preferred
AES guidelines. Epilepsy currents.20

PART trial completed in 2012 showed, IM midazolam is superior to IV lorazepam

n used by paramedics due to the time required to achieve IV access for IV loraze
 Efficacy of 2nd line AED for
established BZD resistant SE
Drug AES guidelines LICE guidelines Neurocritical
care society
guidelines
Phenytoin Level U(only for Grade B Level B
fosphenytoin)
Valproate Level B Grade A Level B
Levetiracetam Level U Grade C Level B
Phenobarbitol Level B Grade A Level B

According to AES guidelines, fosphenytoin is better tolerated and

should be
preferred whenever possible (level B), but insufficient data for
comparable efficacy of both (level U)
 Recommended doses of AEDs for
established SE
Name of AED Recommended dose
Phenytoin
20 mg/kg diluted in NS @ max 1

mg/kg/min(max 50 mg/min) (can repeat 10

mg/kg)(max dose 1 gm)

Fosphenytoin
20 mg/kg PE@ max 3 mg/kg/min(max 150

mg/min)
Valproate
20-40 mg/kg @ max 6 mg/kg/min(max 3 gm)
Levetiracetam
20-60 mg/kg@ max 5 mg/kg/min(max 4.5 gm)
Phenobarbitol
20 mg/kg@ max 2 mg/kg/min(max 50 mg/min)
Valproate is to be used with caution in young children due to risk of
(max 700 mg)(can repeat twice 10 mg/kg if
hepatotoxicity
In case of metabolic liverseizure
disease
not controlled) AES guidelines. Epilepsy currents.2016
Brophy et al. Neuro crit care.2012
 Phenobarbitone coma protocol
Inj Phenobarbitone 10 mg/kg slow infusion over 15 minutes
•Taper inj midazolam @0.5 ug/kg/min each
hour
•If the child is on ventillator than maintain@
1-2 ug/kg/min
Monitoring
•Vitals ,
Inj Phenobarbitone infusion
pulses, BP,
Bowl •Start@1 mg/kg/hour
sounds •Increase@0.5 mg/kg/hour every 6 hourly upto maximum 3 mg/kg/hou
•CXR, EEG•Titrate dose with EEG to achieve
1. Burst suppression
6hrly, drug
level 2. <25% epileptiform discharges as compared to base line
24hrly,
sepsis work
When target EEG is attained, maintain phenobarbitone infusion for next 24-48
up

uce phenobarbitone infusion by 0.5 mg/kg/hour every q6hourly to reach 0.5 mg/k

Convert to inj phenobarbitone 6 mg/kg/dose q12hourly

Decrease to inj phenobarbitone 4 mg/kg/dose q12 hourly over 5-7 day

 Treatment algorithm for
refractory SE
Midazolam and/or high dose phenobarbitone infusion

Suspected autoimmune epilepsy:

May consider other AEDs like steroid, IVIg, plasma exchange, Rituxima
topiramate, lacosamide
IV magnesium and IV
pyridoxine(if already
previously not tried in <2
Thiopentone, propofol, year)
Emergency
ketamine or Pentobarbitol
neurosurgery if definite
infusion
localization possible in
EEG and/or
neuroimaging
Inhalational anesthetics(isoflurane,depending
desflurane)on feasibility

KD, therapeutic hypothermia,Vagal nerve stimulation,

electro convulsive therapy, deep brain stimulation
 Management of super refractory
SE
SE continuing for at least 24 hour after initiation of
general anesthetic medications, including cases in which
SE recurs with reduction of anesthesia are called SRSE

•Only case series,few retrospective studies and review

articles available for management of super refractory status
epilepticus.
•Following modalities available for management of super
refractory SE
1. Ketamine infusion and inhalational anesthetics(if not tried
already)
2. Immunotherapy(especially if autoimmune causes
supected)
3. Magnesium infusion
4. Ketogenic diet Brophy et al.Neuro crit care.2012
Continuous EEG
monitoring
 Initiate within 1 hour of suspected RSE
 Duration of cEEG monitoring-at least 48 h following
acute brain insult in comatose patients
 At least for 24 h after cessation of electrographic
seizures or during the AED weaning trials
 Treatment endpoints from EEG
-Burst suppression
-complete background suppression
-Seizure suppression
No Indian Pediatric studies on the role of cEEG
monitoring in RSE

Shorvan S et al.Brain.201
 cEEG end points in treatment of
refractory SE
EEG defined endpoint Rationale Level of evidence
Cessation of non Recurrent non- Level B
convulsive seizures convulsive seizures
result in ongoing
brain injury and
worsen mortality
Diffuse beta activity Verifies effect of Level C
anesthetic agents
Burst suppression 8- Interruption of Level C
20 second intervals synaptic transmission
of electrical activity
Complete Interruption of Level C
suppression of EEG synaptic transmission

Brophy et al.Neuro crit care.2012

roposed protocol for status epilepticus in child

•Inj.Lorazepam 0.1mg/kg iv (max-4mg) •General measures: Airway,

@2mg/min or
•Inj.Midazolam 0.15-0.2 mg/kg IV (max-5mg)
or
•Inj Diazepam 0.2-0.3 mg/kg IV(max 10 mg)
0 min If IV access is not available,
• Inj midazolam 0.3 mg/kg IM(max 5 mg for
children 13-40 kg) or
•Intransal midazolam 0.2mg/kg (max-10 mg)
or
• Per-rectal diazepam 0.5mg/kg (max-20 mg)
Breathing, Circulation to be
established, recovery osition
•Investigations:Glucose,Sodium,
Potassium,Calcium,Magnesium,
CRP,AED levels, LFT, RFT,
toxic screen.
•Monitoring of cardiorespiratory
status/ Oxygenation

Inj.Phenytoin 20mg/kg in NS (max-1000mg) @ 1mg/kg/min maximum or

5-20 min Inj.Fosphenytoin PE 20mg/kg @ 3mg/kg/min maximum

Established SE Repeat Inj.Phenytoin 10mg/kg if there is no response
 •Inj.Valproate 20-40 mg/kg iv @max
6mg/kg/min (or)
•Inj.Phenobarbitone 20mg/kg iv @max 2
mg/kg/min
Refractory • If no response, repeat inj.Phenobarbitone 10 •Continuous monitoring,
SE(even after mg/kg IV and can repeat 10 mg/kg once more plan for CT head,LP and
(or) EEG,
10 min of
• Inj.Levtiracetam 20mg/kg @ 5mg/kg/min •Vasopressors if needed
phenytoin (safe in children with coagulopathy,
administratio chemotherapy, metabolic and liver diseases)
n)

Consider iv pyridoxine 100mg infusion in children less than 2 years or in isoniazid overdose
Coma induction: If seizures continue for 10 minutes after completion of phenobarbitone infusion ,shift
to PICU 

Just before coma induction, topiramate loading may be tried or it may be subsequently tried
on individual basis(Dose: 2-5 mg/kg enteral loading, increase by 5-10 mg/kg/d upto maximum
of 25 mg/kg/d)
• Inj Midazolam-0.2 mg /kg bolus then infusion @ 1 μg/kg/min, increasing 1 μg/kg/min, every 5- 10
min, till seizures stop, upto a maximum of 30 μg/kg/min, start tapering 24 h after seizure stops or burst
suppression on EEG @ 1 μg/kg/min, every 3 h
• Intensive care: Consider intubation and mechanical ventilation. Monitoring of cardiorespiratory status,
Identify and treat raised ICP

If seizures persist on midazolam infusion

•High dose Phenobarbitone: Bolus of 10 mg/kg over 15 min f/b phenobarbitone infusion at 1
mg/kg/hour, increase @0.5 mg/kg/hour q6hourly upto maximum 3 mg/kg/hour, target burst suppression
or <25% discharges on EEG as compared to baseline, then tapering @0.5 mg/kg/hour every 6 hourly
•Inj Thiopentone: Loading Dose: 5 mg/kg bolus followed by 3-5 mg /kg /hr infusion rate to achieve
burst suppression. Start tapering after 24 h seizure free period
•Short-term Propofol: Initial bolus of 1-2 mg/kg, followed by a continuous infusion of 1-2 mg/kg/hour
and titrated to a maximum of 5 mg/kg/hour. Limit use to < 48 hrs.
•Ketamine- IV Load 1.5 mg/kg followed by 10-50 ug/kg/hr. start tapering after 24 hr of seizure free
period
 Consider in those relapsing on tapering
• Topiramate–2-5 mg/kg loading; increase by 5- 10 mg/kg/d to maximum of 25 mg/kg/d
• Inj Lacosamide 2.5-5mg/kg (max dose 200-400mg) IV

•Topiramate (if already not tried

previously)
•Inhaled anesthesia(Isoflurane or General
Desflurane) measures
>24 hours •Reviewing
Super refractory SE •Ketogenic diet(especially in FIRES, the diagnosis
focal seizures, autoimmune)
•Immunotherapy(especially •Involving
autoimmune; Steroid, IVIg, plasma subject
exchange) experts
•Magnesium infusion •Presurgical
•Epilepsy surgery evaluation
•Controlled hypothermia(32-35 degree)