2012 NEURO CRITICAL CARE GUIDELINES FOR SE

1. DR. SAMRAT A SHAH
DEPARTMENT OF NEUROLOGY

2.  Worldwide incidence of Convulsive Status
Epilepticus
- 3.8 to 38 per lakh per year in children.
- 6 to 27 per lakh per year in adults.
 Bimodal peak distribution, with peaks in children
and elderly.
 Frequency of refractory status epilepticus in status
epilepticus patients = 31-44%
J K Murthy Convulsive status epilepticus API 2013

3.  In approximately 50% cases, there is no prior
history of epilepsy.
 Males are affected more compared to females
partly attributed to lower seizure threshold in
males.
 Mortality rates range between 10.5-28%.
 Neurological or cognitive sequelae in convulsive
SE occur in 11- 16 % patients.

4. 1. Low AED levels - 35%
2. Stroke, including haemorrhagic - 20%
3. Alcohol withdrawal - 15%
4. Anoxic brain injury - 15%
5. Metabolic disturbances - 15%
6. Remote brain injury/ cong. malformations - 20%
7. Infections - 5%
8. Brain neoplasms - 5%
9. Idiopathic - 5%

5.  According to an Indian study, the etiology of Status
Epilepticus was Infection in 53.8%, drug default in 7.9%,
metabolic in 14.5%, Stroke in 12.8% and miscellaneous in
11% of patients.
 Infection as an etiology was more common in children, drug
default and metabolic causes in adult and stroke in elderly.
 Mortality = 29% (elderly >> children)
(A clinical, radiological and outcome study of status
epilepticus, India J Neurology (2010) 257:224-229)

6.  The first definition of Status Epilepticus came from
Clark and Prout as “ maximal development of
epilepsy in which seizures are so frequent that coma
and exhaustion are continuous between seizures.”
 The first official definition of SE was the product of
10th Marseilles Colloquium (1962) which was
accepted by International League Against Epilepsy
(ILAE) in 1964 and modified in 1971 as “a seizure
that persists for sufficient length of time or repeated
frequently enough that recovery between attacks
does not occur.”

7.  Status Epilepticus is defined as 5 minutes or
more of :
1.continuous clinical and/or electrographic
seizure activity or
2. recurrent seizure activity without
recovery (returning to baseline) between
seizures

8.  Series of generalized tonic-clonic seizures
without return to consciousness in between
seizures or a single prolonged seizure without
charecterstic evolution of single discrete
seizure.
 SUBTLE SEIZURE: Profound coma,convulsive
activity has only subtle twitches of extremities
or trunk or nystagmoid movements of eyes
and bilateral ictal discharges on EEG.

9.  Initial compensatory phase-sympathetic overdrive
a. increased CO.
b. increased BP
c. increased BS
d. increased blood lactate levels
 Decompensation –homeostatic failure
1. Cardiorespiratory collapse
2. Electrolyte imbalance
3. Rhabdomyolysis & delayed tubular necrosis
4. Hyperthermia
5. Multi organ Failure
6. Raised ICP & cerebral edema

10.  Two types:
 COMPLEX PARTIAL SE.
 ABSENCE SE.
 Duration of seizures doesn’t affect prognosis in
NCSE.

11.  Post ictal confusion following a CPSE is not
said to be SE.it is nonepileptiform cortical
disturbances.
 Prolonged Postictal confusion can sometimes
be due to continued seizure activity either
localized or diffuse following a discrete
seizure.

12. Etiology:
 Most commmon cause: AED change
Other causes:
 Stroke
 Encephalitis.
 Old glioma, scar, tumour, hemartoma
 Precipitating factors include alcohol, drug
withdrawal, stress, sleep deprivation.

13.  Wide variety of presentation which may be
indistinguishable from ASE.
 Can have 2 types of presentation:
 Continues activity or recurrent cyclic activity.
 CPSE usually has cyclic seizure activity with
with incomplete clearing between episodes.
 Impairement of conciouness is must, in form
of continues or fluctuating confused state to
agitated unresponsiveness with psychotic
activity.

14.  Defined as a prolonged or serial typical
absence attacks that were sufficiently close
together to give rise to prolonged
disturbances in consciousness and EEG
pattern of classic ictal 3hz spike wave pattern.
 Alteration of consciousness is less profound in
Absence SE then in typical absence attacks.

15. 1. TYPICAL ASE:
 Simple confused state at times with subtle jerks
of eyelids,with rhythmic 3hz swd.
 Prognosis is excellent.
2. ATYPICAL ASE:
 Seen in patients with generalized seizures
characterized by fluctuating confusional states
with predominant tonic,clonic,atonic ,myoclonic
and lateral ictal manifestations.
 Immediate prognosis is guarded.

16. 3.ASE WITH FOCAL FEATURES:
 Seen in cases of preexisting or newly developing
lateralized seizures most often extra temporal in
origin.
 EEG shows bilateral asymmetrical ictal discharges.
4.ASE OF LATE ONSET:
 Middle aged or elderly adults.
 Extreme end of continum of childhood epilepsy.
 Usually in 6 decade.
 Most common cause being withdrawal of
pyschotropical drugs.

17.  Couding of conciousnes is divdied into 4 grades:
1. Slight : complains of bad days
2. Marked: most typical, frank confusion seen.
3. Profound: limited motor and verbal response.
4. Lethargic stupor: catatonia,motionless with
incontinence.
 Myoclonus: bilateral jerky movements of face,
eyelids and arms with little impairment of
consciousness with eyes closed.

18.  Defined as: Clinical or EEG signs and
symptoms of at least 30 min duration with
spectrum of large ictal manifestations as well
as subtle clinical signs with some behaviour
disturbances and psychosis like state in
particular hallucinations without loss of
consciousness or severe alteration in
consciousness.

19.  EPILEPSIA PARTIALIS CONTINUA: Partial
somatomotor SE for minimum of 1 hour and
recurring at regular intervals of no more then
10 seconds and as spontaneous regular or
irregular clonic twitching of cerebral cortical
origins sometimes aggravated by action or
sensory stimulus confined to one part of body
and continuing for hours,days,weeks.

20.  Refractory status epilepticus
 Do not repond to standard treatment regimen
for status epilepticus (adequate doses of intial
BZD followed by a second acceptable
antiepileptic drug )
 Nearly 40% of status epilepticus are
refractory.
 Predictors- encephalitis / nonstructural
causes(HIE) / delayed diagnosis & treatment .

21.  Malignant / Super- refractory status
epilepticus
 Status epilepticus that does not respond to a
course of anesthetic drug.
 20% of refractory status epilepticus patients.
 Needs combination therapy (AED &
Anesthetic drugs) .

22. MANAGEMENT OF STATUS EPILEPTICUS

23. Aims of management of Status Epilepticus are as
follows :-
1. Termination of Status Epilepticus
2. Prevention of Seizure Recurrence
3. Management of Precipitating cause
4. Management of complications

24. All patients
• Obtain IV access
• Monitor vital signs (ABC).
• Head CT (appropriate for most cases)
• Labs: blood glucose, CBC, renal function tests, Calcium,
Magnesium, electrolytes, AED levels.
• cEEG monitoring (preferably)
Consider based on clinical presentation
• Brain MRI
• Lumbar puncture
• Toxicology panel (i.e. isoniazid, TCAs, theophylline, cocaine,
sympathomimetics, organophosphates, cyclosporine)
• Other relevant investigations as per the need
Brophy, et al NCC 2012

25. •The use of cEEG is usually required for the treatment of SE.
•Continuous EEG monitoring should be initiated within 1 h of SE
onset if ongoing seizures are suspected.
•The duration of cEEG monitoring should be at least 48 h in
comatose patients to evaluate for non-convulsive seizures.
Brophy, et al NCC 2012

26. Brophy, et al NCC 2012
• Recent clinical seizure or SE without return to
baseline >10 min
• Coma, including post-cardiac arrest
• Epileptiform activity or periodic discharges on initial
30 min EEG
• Suspected non-convulsive seizures in patients with
altered mental status

27. Brophy, et al NeuroCritical Care 2012
• Cessation of non-convulsive seizures
• Diffuse beta activity
• Burst suppression 8–20 s intervals
• Complete suppression of EEG

28.  Give glucose (100 ml D25%), unless normo- or
hyperglycemic
 Hyperglycemia has no negative effect in SE
 (as long as significant hyperosmolality is being
avoided)
 Thiamine 100 mg IV - if given D25 or if
malnourished/alcoholic

29.  The longer we wait with anticonvulsant, the
more anticonvulsant we will need to stop SE
 Most common mistake is ineffective dose.
 Benzodiazepines
 Lorazepam 0.1- 0.15 mg/kg i.v upto 4-6 mg over 1-2
minutes
If SE persists, repeat every 5-10 minutes

30.  If lorazepam is successful in stopping GCSE, the
decision to add another agent depends on the
underlying etiology.
 Lorazepam’s duration of action is approximately
12 to 24 hours.
 If the etiology is reversible (e.g., status
epilepticus due to metabolic or toxic factors),
lorazepam may be the only treatment necessary.
 Another longer-acting AED is needed if the
underlying etiology is not rapidly reversible

31.  Phenytoin:- 20mg/kg Bolus dose IV at the
rate of 50mg/min.
 Fosphenytoin:- 20mg /kg Bolus dose IV
at the rate of 150mg/min
(Repeat dose of 10mg/kg can be given)

32.  -general anesthesia should be induced
 Propofol:- 2mg/kg IV bolus,Repeat if necessary,
followed by infusion (2 – 10 mg/kg/hr)
 Thiopental:- 100-250mg IV bolus over 20 sec. with
further 50mg bolus every 2-3 min.until seizure control
followed by IV infusion(3-5mg/kg/hr)
 Midazolam:- 0.3mg/kg IV bolus dose at the rate of
4mg/min, rpt every 5 min 3 doses followed by
infusion(2 ug/kg/hr)
If seizures have been controlled for 12hrs., reduce
the dose over further 12hrs.
If seizure recurs again GA agent should be given

33. STATUS EPILEPTICUS
Rapid IV access available
NO
IM Midazolam 0.2mg/kg (max10mg)
OR
Buccal or Intranasal Midazolam
0.5mg/kg (max10mg)
YES
IV LORAZEPAM 0.1mg/kg slow push (max 4mg)
Repeat IV LORAZEPAM 0.1mg/kg
slow push
If Seizure donot
stop in 5 minutes
If Seizure donot
stop in 5 minutes,
Achieve IV access
Shift to 2nd line drugs
If Seizure donot
stop in 5 minutes
IV Phenytoin 20mg/kg @ 50mg/min
OR
IV Fosphenytoin 20mg/kg @ 150 mg/min
If Seizure donot stop in 20 minutes
If possibility of
subttherapeutic levels,
Valproate 40-60 mg/kg @ 6
mg/kg/min can be tried
If Seizure
donot stop in
10 minutes

34. Repeat IV Phenytoin 5mg/kg OR
IV Fosphenytoin 5mg/kg
IV Phenobarbitone 20mg/kg @ 100mg/min f/by 3-5
mg/kg.hr cont infusion
OR
IV Midazolam 0.2 mg/kg loading dose f/by 0.1-0.4
mg/kg/hr cont infusion
OR
IV Propofol 2mg/kg bolus f/by 2-10 mg/kg/hr cont
infusion
OR
IV Pentobarbital 5 mg/kg loading dose f/by
1-3 mg/kg/hr cont infusion
If seizure persists after 24 hrs, try emerging novel therapies: Ketamine bolus 0.5-4.5
mg/kg infusion (upto 5 mg/kg/hr ) ; Immunomodulation IV Methylprednisolone or
IVIg; Resective surgery ; Ketogenic diet ; hypothermia
Alternative
drug
Valproate 40-
60 mg/kg @ 6
mg/kg/min
Alternative
Drug
Levitiracetam
20-30mg/kg
@ 5
mg/kg/min
Seizure not
controlled
Seizure not
controlled

36.  Drug of choice for out of hospital as well as in-
hospital treatment.
 Effective in terminating seizures in 59-78 % cases.
 Lorazepam is the DOC for IV administration.
 Midazolam is the DOC for IM administration.
 Rectal Diazepam is effective in children.
 Other routes are buccal Midazolam and intranasal
Midazolam (not commonly used)

37.  Benzodiazepines
Diazepam
 10mg IV push over 30-60 seconds
 repeat after 10-15mins, upto 40mg (5mg/min)
Repeat after 2-4hrs. (max 100mg/day)
 bolus dose should be given in undiluted form at
rate not exceeding 2-5 mg/min.
 Lorazepam
0.1- 0.15 mg/kg i.v, upto 4-6 mg over 1-2 minutes
If SE persists, repeat every 5-10 minutes

38.  Diazepam
One of the drug of choice for first line management of SE
 Good results, easy to administer. (fast acting, short
lasting)
 More lipid soluble, hence short distribution half-life.
• Anti-seizure effect 15-30min.
• Sufficient cerebral levels are achieved within 1 min of
IV administration and about 20 mins after rectal
administration.
• Elimination half life abt 24 hrs (may accumulate)
 Side effects -- hypotension, bradycardia,
respiratory depression, cardiac arrest,
tolerance, depresses mental status.
 In children and elderly :
Rectal Diazepam 0.5 mg / kg in children and 10 mg
in elderly are also good alternatives.

39.  Lorazepam
 Has emerged as preferred BZD for treatment of SE
 The veteran affairs (VA) co-operative study demonstrated
advantage of IV Lorazepam over Phenytoin.
• Less lipid distribution with distribution half life of 2-3 hours
• So Fast acting, longer lasting compared to Diazepam
 Longer therapeutic half-life.
 Anti-seizure effect for 6-12hrs.
 2mg dose, upto a max dose of 8mg in total
 Main disadvantage is rapid development of tolerance, hence
repeated doses are less effective and has no role in long term
therapy.

40.  - If Benzodiazepines are successful in stopping
 GCSE, the decision to add another agent
 depends on the underlying etiology.
 - If the etiology is reversible (e.g. metabolic or
 toxic factors), BZDs may be the only treatment
 necessary.
 - Another longer-acting AED is needed if the
 underlying etiology is not rapidly reversible.

41.  In patients taking Sodium Valproate -25mg/kg iv
sodium valproate can be tried who may be sub
therapeutic.
 Phenytoin:- 20mg/kg Bolus dose IV at the rate of
50mg/min.
 Fosphenytoin:- 20mg PE/kg Bolus dose IV at the
rate of 150mg/min
 Above drugs have advantage that they lack sedative
effects.

42. 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

43.  So Fosphenytoin injection has the following advantages over
phenytoin
100% bioavailability
better tolerated at site of injection.
can be given IV more rapidly .
can be given IM when cardiac monitoring is not necessary
 But has the following disadvantages
 conversion of fosphenytoin to phenytoin takes about 15
minutes. Hence inappropriate for the initial treatment of
status epilepticus (SE).
 transient paraesthesia and pruritus occur more frequently
than with phenytoin.
 the use of phenytoin equivalents may be confusing.

44.  Used in SE when BZD and Phenytoin have
failed.
 Loading dose – 15-20 mg/kg
 Causes sedation and hypotension, so airway
protection should be done.
 Diluted in Polyethylene Glycol which results in
complications like renal failure, myocardial
depression and seizures.

45.  FDA approved use in SE in 1997
 Parenteral loading is done when oral therapy is not
possible.
 Broadspectrum action and is also useful in absence
and myoclonic SE.

46.  Is used as an alternative to Diazepam in early SE where IV
administration is difficult or conventional AED are
contraindicated or proved ineffective.
 Given rectally or I/M with fast and complete absorption with
rapid onset of action.
 Seizure tend to recur after initial control.
 Inappropriately diluted or decomposed drug is highly toxic.
 Given at a dose of 10-20ml of 50% solution rectally or I/M.
 Diluted in NS for rectal or I/M route.
 For I/V route, given as a 5 % infusion in 5% dextrose, freshly
prepared up every 3 hours.

47. Brophy, et al NCC 2012
•Refractory SE therapy recommendations should consist of
continuous infusion AEDs, but vary by the patient’s underlying
condition
•Dosing of continuous infusion AEDs for RSE should be titrated
to cessation of electrographic seizures or burst suppression
•During the transition from continuous infusion AEDs in RSE, it
is suggested to use maintenance AEDs and monitor for
recurrent seizures by cEEG during the titration period.
•A period of 24–48 h of electrographic control is recommended
prior to slow withdrawal of continuous infusion AEDs for RSE

48.  Seizures continuing / Stage of Refractory Status
 -General anesthesia should be induced
 Propofol:- 2mg/kg IV bolus,Repeat if necessary, followed by
infusion (2 – 10 mg/kg/hr)
 Thiopental:- 100-250mg IV bolus over 20 sec. with further
50mg bolus every 2-3 min.until seizure control followed by IV
infusion(3-5mg/kg/hr)
 Midazolam:- 0.3mg/kg IV bolus dose at the rate of 4mg/min,
rpt every 5 min 3 doses followed by infusion(2 ug/kg/hr)
 Neuromuscular Blocking Agents :
If seizures have been controlled for 12hrs., reduce the
dose over further 12hrs.
If seizure recurs again GA agent should be given

49.  No difference has been found in mortality in groups
treated with either of these agents.
 Pentobarbital was associated with lower frequency
of acute treatment failures and breakthrough
seizures.
 Superior pharmacokinetics and adverse effects
profile makes Propofol preferred drug in Refractory
status epilepticus in children as well as adults

50.  Barbiturate anesthetic given in ICU setting as patient
requires intubation and mechanical ventilation.
 Most troublesome S/E- hypotension (may require
pressor therapy)
 Tendency to accumulate
 Caution advised in elderly or in cardiac, hepatic or
renal diseases.
 100-250mg bolus over 20 secs, with further 50mg
boluses every 2-3 mins till seizures are controlled
with maintenance dose as 3-5mg/kg/hr.
 Aqueous solution is unstable if exposed to air.

51.  Nonbarbiturate anesthetic
 Highly lipid soluble with high volume of
distribution resulting in rapid and short lived
action.
 Causes profound respiratory and cerebral
depression requiring assisted ventilation.
 May cause involuntary movements which are
not to be confused with seizures
 2 mg/kg bolus dose followed by 5-10
mg/kg/hr infusion.

52.  S-enantiomer of Piracetam
 Was introduced for treatment of SE in 2006
 Insufficient data on safety and efficacy of this
drug in status epilepticus.
 Several case reports its use in SE.
 European federation of neurological societies
proposes its usefulness in refractory complex
partial SE. (Meiekord H et al, EFNS guideline on the management of
status epilepticus in adults, Eur Journal 2010)

53.  Levetiracetam has been used to control SE, typically
as second line drug.
 Levels peak within 2 hrs. Steady state in 2 days. No
significant interactions.
 Mishra et al (2012) used LEV 20 mg./kg over 15 min.
and compared with Lorezepam 0.1 mg./kg over 2 to
4 min. in 79 patients. Control was comparable
(76.3% and 75.6%). 24 Hour seizure control was also
similar. But hypotension and requirement of
mechanical ventilation was significantly higher in
Lorezepam group.

54. Thongplew and collegues reviewed the clinical use, efficacy, and
outcomes of intravenous levetiracetam in adults with status
epilepticus.
Results:
• 34 prescriptions for intravenous levetiracetam in patients with
status epilepticus were noted.
• All patients had at least one co-morbidity condition
• The seizure control rate was 61.8%
• 41.2% survived and had an improved status at discharge.
Neurology Asia 2013; 18(2) : 167 – 175
Intravenous levetiracetam has good efficacy and may be a good option
for status epilepticus.

55. Randomized, open labeled pilot study compared the efficacy and safety of
levetiracetam and lorazepam in status epilepticus.
 Patients with convulsive or subtle convulsive SE were randomized to
Levitiracetam 20 mg/kg IV over 15 min or Lorazepam 0.1 mg/kg over 2-4
min.
J Neurol. 2012 Apr;259(4):645-8
Levetiracetam Lorazepam
In first instant,
SE controlled
76.3 75.6
In those resistant,
SE controlled
70.0 88.9
24-h freedom
from seizure
79.3 67.7
Lorazepam
• Significantly higher need
of artificial ventilation
• Insignificantly higher
frequency of hypotension
For the treatment of SE, levetiracetam is an alternative to lorazepam and may
be preferred in patients with respiratory compromise and hypotension.

56.  Christian et al (2010) reported successful
termination of refractory SE given 22.5 mg.
diazepam, 12.5 mg. etomidate & 5 mg. midazolam, 4
mg. lorazepam & 1500 mg. levetiracetam.
Lacosamide 300 mg via per cutaneous gastric fistula
resulted in cessation of SE in 30 min.
 Kellinghaus (2009) reported successful termination
of SE with IV Lacosamide.
 However furthere large RCT are required to prove
the efficacy and safety of this drug in SE.

57.  In addition to anticonvulsant property, it has shown
potential to retard kindling induced epileptogensis.
 One report shows efficacy in Nonconvulsive
SE.(Kellinghaus C et al, Epilepsy Behav 2009)
 One report showed efficacy of oral Lacosamide in
refractory convulsive SE.(Tilz C et al, Epilepsia 2010)

58.  Along with emergency control of SE,
maintenance therapy should be started to
prevent recurrence of seizures.
 In patients known to have epilepsy, their usual
AED can be continued depending on serum
AED levels.
 In patients presenting for the first time as SE,
drugs like Phenytoin or Sodium Vaproate used
to control the status can be continued as
maintenance therapy.

59.  Inhalational Anaesthetic agents
(isoflurane and 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.
Mirasattari et al, treatment of refractory status epilepticus with inhalational
anaesthetic agents : Isoflurane & Desflurane , Arch Neurology 2004

60. 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 doesnot cause
hypotension.

61.  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.

62. Steroids and Immunotherapy
 Rationale that refractory SE may be due to
antibodies directed against neural elements.
 Increasing recognition the role of inflammation in
epileptogenesis.
 SE may be the initial presenting feature of some
immune mediated encephalopathies.

63.  Resective surgery
 Vagal nerve stimulation
 Hypothermia- decrease brain metabolism
which is neuroprotective.
 Electroconvulsive therapy - ECT-dose-1
session daily for 3-8 days. Mechanism-not
known

65.  Textbook of epilepsy by JEROME ENGEL,PEDLEY
 Guidelines for evaluation and management of status
epilepticus Neurocritical Care Society 2012