Fitri Octaviana

Neurology Department, Faculty of Medicine

University of Indonesia
Status epilepticus (SE) is a major medical
emergency
affecting between 120,000 and 200,000 people
in USA annually.
The estimates of the frequency of refractory SE
vary from approximately 10% to 40%.
Failure to diagnose and treat SE accurately
and effectively results in significant morbidity
and mortality.
continuous seizure activity lasting 30
minutes or more
OR
intermittent seizure activity lasting 30
minutes or more during which
consciousness is not regained
the time when patients should be treated as
if they were in established status
epilepticus durations as low as 5 minutes

Raspall-Chaure M et al. Epilepsia 2007;48(9):1652-1663

Convulsive Non-Convulsive
General Tonic-clonic (grand mal)
Tonic
Myoclonic

Absence (petit mal)
Partial Partial motor Complex partial
Chapman MG. Anaesthesia 2001;56:648-659

SE is usually easily diagnosed by observation.
Convulsive are characterized by loss of
consciousness, tonic-clonic muscle
activity, foamy mouth, tongue biting,
upward eye gaze and urinary incontinence.
The differential diagnosis of SE includes
generalized dystonia and pseudostatus
epilepticus.
Pseudostatus epilepticus consists of seizures that
are psychogenic in origin.

Non-convulsive SE is more difficult to
diagnose.
Clinical features include impairment of
consciousness, agitation, aphasia, amnesia
confusion, nystagmus.
Diagnosis can only be confirmed definitively
by EEG examination.
In a study, 8% of coma patients showed
non-convulsive SE.

Agitation
Anorexia
Aphasia
Amnesia
Automatisms
Blinking
Catatonia
Coma
Confusion

Crying
Delirium
Delusions
Echolalia

Nause
Nystagmus
Personality
changing
Psychoses

MONITORING EEG is NECESSARY!
Figure 2. EEG of a 20 yo female with amnesia
Many SE cases arise in patients with
acute neurological or medical illnesses.
Approximately 50% of cases occur in the
absence of previous epilepsy.
Individuals with history of epilepsy are at
risk of developing SE.
Etiology of SE may be divided into acute
and chronic processes
Acute processes Chronic processes
Electrolyte imbalance Pre-existing epilepsy
Cerebrovascular accident Poor anticonvulsant drug
compliance or change of
anticonvulsant therapy
Cerebral trauma Chronic alcoholism
Drug toxicity Cerebral Tumour
Cerebral anoxichypoxic
damage
CNS infection
Sepsis Syndrome
Renal failure
Etiology of Status Epilepticus
ILAEs recommended classification of status epilepticus
according to etiologies (Gastaut, 1983; ILAE commision on
Epidemiology and Prognosis,1993)
Acute symptomatic SE in a previously neurologically normal
child, within a week of an underlying etiology including CNS
infection, prolonged febrile seizures, encephalopathy, head
trauma, cerebrovascular disease, and metabolic or toxic
derangements
Remote symptomatic SE in the absence of an identified acute insult
but with a history of a pre-existing CNS abnormality more than 1 week
before
Idiopathic epilepsy related SE that is not symptomatic and occurred
in children with a prior diagnosis of idiopathic epilepsy or when the
episode of SE is the second unprovoked seizure that has led to a
diagnosis of idiopathic epilepsy
Contd..
Cryptogenic epilepsy related SE that is not symptomatic and
occurred in children with a poor diagnosis of cryptogenic epilepsy
or when the episode of SE is the second unprovoked seizure
that has led to a diagnosis of cryptogenic epilepsy
Unclassified SE that cannot be classified into any other groups
3
6.1
10.6
3
7.6
48.5
21.2
72.7
21
0 20 40 60 80
Brain trauma
CNS infection
Toxic/med/drug
Unknown
Mortality
Percentage
Percentage
Etiology of GCSE
Ismir Turkey; Sagduyu et al 1998
N = 66 Brain tumor
Acute CVA
Drug Withdraw
Prior Epilepsy
Prolonged seizure permanently neuron
damage

Brain
Injury
Phase 1
metabolic demand is increased that caused by abnormally
discharging cerebral cells and then make an increasing of
arterial blood pressure and autonomic activity.
This process results in increase arterial blood pressure,
increased blood glucose levels, sweating, hyperpyrexia and
salivation.
Phase 2 (happened after 30 minutes of Phase 1)
Characterized by failure of cerebral autoregulation, decreased
cerebral blood flow, an increase of intracranial pressure and
systemic hypotension.
These result in a decrease of cerebral perfusion pressure.
Phase 1 Phase 2
Neurophysiologic changes of SE
Systemic complication of generalized
convulsive SE can affect:
central nervous system (cerebral hypoxia, cerebral
edema, cerebral hemorrhage)
cardiovascular system (myocardial infarction,
arrhythmia, cardiac arrest)
respiratory system (aspiration pneumonia,
pulmonary hypertension, pulmonary embolus)
metabolic derangements (dehydration, electrolyte
disturbance, acute tubular necrosis)
Therapy should proceed simultaneously
on 4 aspects:
1. termination of SE
2. prevention of seizure recurrence once SE
is terminated;
3. management of precipitating causes of SE;
4. management of complications.




The primary principles of emergency
management are basic life support:



maintenance of the airway
ensuring an adequate circulation
maintenance of breathing
The airway must be maintained from the
earliest stages
tracheal intubation will be needed so
adequate ventilation can be ensured and
pulmonary aspiration can be prevented.
Monitoring should be initiated (ECG,
measuring blood pressure and pulse
oxymetri) in all patients.

Measurement of blood glucose should be
made.
If there is significant hypoglycaemia, glucose
40% 50 ml should be administered.
If there is a history or suspicion of alcoholism,
intravenous thiamine 100 mg should be given
along with glucose to avoid precipitating
Wernickes encephalopathy.

A careful history from relatives might highlight
precipitating factors such as a recent change in
anticonvulsant medication, alcohol withdrawal,
drug overdose, and stroke or central nervous
system infection.

CT Scan or MRI of brain might be needed that can
reveal a focal process.

Cerebrospinal fluid examination might also be
indicated in the absence of raise intracranial pressure
The main goal of therapy is:
the rapid and safe termination of the
seizure and
prevention of its recurrence.
Benzodiazepine (Lorazepam,Diazepam)
Phosphenytoin/Phenytoin.
Midazolam.
Propofol.
Valproate.
Phenobarbital
Pentobarbital
Act as agonists at GABAA receptors and
potentiate inhibition of neuronal firing.
Rapidly acting and therefore have a place in
the control of SE.
Intravenous (IV) lorazepam 0.1mg/kg is widely
considered to be the drug of choice for the
acute management.
But since lorazepam IV is not available in
Indonesia, diazepam IV 0.2mg/kg (10-20 mg)
is considered to be the drug of choice in our
country.

Diazepam has a very short effective duration of
action because of rapid redistribution to body
fat stores.
Diazepam can be given by the rectal route.
All benzodiazepine cause sedation and
respiratory depression, and repeated doses
have a cumulative effect.
The sedative effects may delay recovery of
consciousness after cessation of SE
Lorazepam Diazepam
Loading dose
Time to stop SE
Duration effect
Elimination half life
Duration of
sedation
SE

4-8 mg.
3-10 min.
12-24 hrs
14 hrs.
Several hours
Respiratory
depression.


10-20 mg
1-5 min.
15-30 min.
30 hrs
15-60 min.
Respiratory
depression
If diazepam fails to stop
seizure activity within 10 min,
or if intermittent seizures
persist for more than 20 min,
another drug should be added
Phenytoin (or fosphenytoin)
remains the drug of choice for
second-line therapy in SE that does
not respond to diazepam.
Phenytoin is highly lipid soluble and
reaches peak levels within 15 min after IV
administration.
The loading dose of phenytoin (15-20
mg/kg) should be given on a strict weight
basis and requires a large vein for
administration because of the high pH of
the solution.
Therapeutic concentration can be
achieved in less than 10 minutes
It should be mixed with normal saline and
concurrent administration of other drugs should
be avoided, as there is a risk of precipitation.
Infusion of phenytoin carries a significant risk
of hypotension and arrhytmias, QT
prolongation ECG and arterial blood
pressure monitoring is necessary.
Cutaneus complication purple glove
syndrome


The use of intravenous Phenobarbital 10-
20mg/kg tends to be limited to the
management of refractory status, in which it is
effective.
Its mechanism of action is to prolong the
inhibitory postsynaptic potential via an action
on GABAa chloride channels.
Phenobarbital does not enter the brain as
rapidly as more lipophilic drugs, but a
therapeutic level is reached in 3 min and is
maintained for many hours.
Side effects of Phenobarbital is excess
sedation, respiratory depression, hypotension.
This is the definitive treatment for refractory SE
and should be undertaken in an intensive care
unit.
Thiopental is a rapidly acting intravenous
barbiturate that has been used in refractory SE.
Thiopental causes hypotension.
Barbiturates are also potently
immunosuppressive and prolonged use
increases the risk of nosocomial infection
Propofol can be used as alternative
Propofol has barbiturate-like and
benzodiazepine-like effects at the GABAa
receptor and has a potent anticonvulsant action
at clinical doses.
An initial bolus of 1 mg/kg is given over 5 min
and is repeated if seizure activity is not
suppressed.
A maintenance infusion should be adjusted to 2-
10 mg/kg/hour until the lowest rate of infusion
needed to suppress epileptiform activity on the
EEG is achieved.
Rapid discontinuation should be avoided
because of the risk of precipitation of withdrawal
seizures.
An intravenous preparation of sodium
valproate has recently been introduced.
Some trials have found the intravenous
formulation of sodium valproate to be
effective with a good side-effect profile.
European studies have reported control
of SE in 80-83% of cases with a dose of
12-15 mg/kg
The overall mortality of status epilepticus in adults is
approximately 25%.
Patients over the afe of 60 years have a higher
mortality (38 %).
Approximately 89% of patients who die during or after
status epilepticus is due to aetiology of the status
Only 2% of deaths are directly attributable to the SE.
First line therapy is effective in controlling seizures in
55 % of cases of SE, so early treatment is very
important.
Patients with uncontrolled SE lasting more than 1 hour
had a mortality rate of 34.8% compared to 3.7% if the
seizures were terminated within 30 min
Fosphenytoin 20mg/kg IV @ 150mg/min
Phenytoin 20mg/kg IV @ 50 mg/min
Diazepam 0.2 mg/kg IV over 1-2 min
(repeat 1x if no response after 5 min)
Fosphenytoin 5-10mg/kg IV @ 150mg/min
Phenytoin 5-10mg/kg IV @ 50 mg/min
Consider valproate
25 mg/kg IV
Seizure continuing
Phenobarbital
20mg/kg IV at 50-75 mg/min
Phenobarbital
(additional 5-10 mg/kg)
Seizure continuing
Anesthesia with midazolam or
propofol
Time (minutes)
Seizure continuing
Seizure continuing
0 10 20 30 40 50 60 70 80
Seizure continuing
Proceed immediately to anaesthesia with
midazolam or poropofol if the patient develops
status epilepticus while in the intensive care unit,
has severe systemic disturbance or has seizure
that have continued for more than 60 to 90 minutes
Fosphenytoin 20mg/kg IV @ 150mg/min
Phenytoin 20mg/kg IV @ 50 mg/min
Diazepam 0.2 mg/kg IV over 1-2 min
(repeat 1x if no response after 5 min)
Fosphenytoin 5-10mg/kg IV @ 150mg/min
Phenytoin 5-10mg/kg IV @ 50 mg/min
Consider valproate
25 mg/kg IV
Seizure continuing
Phenobarbital
20mg/kg IV at 50-75 mg/min
Phenobarbital
(additional 5-10 mg/kg)
Seizure continuing
Anesthesia with midazolam or
propofol
Time (minutes)
Seizure continuing
Seizure continuing
0 10 20 30 40 50 60 70 80
Seizure continuing
Proceed immediately to anaesthesia with
midazolam or poropofol if the patient develops
status epilepticus while in the intensive care unit,
has severe systemic disturbance or has seizure
that have continued for more than 60 to 90 minutes
Time (minutes)
0

10

20

30

40

50

60

70

80

Fosphenytoin 20mg/kg IV @ 150mg/min
Phenytoin 20mg/kg IV @ 50 mg/min
Diazepam 0.2 mg/kg IV over 1-2 min
(repeat 1x if no response after 5 min)
Fosphenytoin 5-10mg/kg IV @ 150mg/min
Phenytoin 5-10mg/kg IV @ 50 mg/min
Consider valproate
25 mg/kg IV
Seizure continuing
Phenobarbital
20mg/kg IV at 50-75 mg/min
Phenobarbital
(additional 5-10 mg/kg)
Seizure continuing
Anesthesia with midazolam or
propofol
Time (minutes)
Seizure continuing
Seizure continuing
0 10 20 30 40 50 60 70 80
Seizure continuing
Proceed immediately to anaesthesia with
midazolam or poropofol if the patient develops
status epilepticus while in the intensive care unit,
has severe systemic disturbance or has seizure
that have continued for more than 60 to 90 minutes
Fosphenytoin 20mg/kg IV @ 150mg/min
Phenytoin 20mg/kg IV @ 50 mg/min
Diazepam 0.2 mg/kg IV over 1-2 min
(repeat 1x if no response after 5 min)
Fosphenytoin 5-10mg/kg IV @ 150mg/min
Phenytoin 5-10mg/kg IV @ 50 mg/min
Consider valproate
25 mg/kg IV
Seizure continuing
Phenobarbital
20mg/kg IV at 50-75 mg/min
Phenobarbital
(additional 5-10 mg/kg)
Seizure continuing
Anesthesia with midazolam or
propofol
Time (minutes)
Seizure continuing
Seizure continuing
0 10 20 30 40 50 60 70 80
Seizure continuing
Proceed immediately to anaesthesia with
midazolam or poropofol if the patient develops
status epilepticus while in the intensive care unit,
has severe systemic disturbance or has seizure
that have continued for more than 60 to 90 minutes
Epilepsia, vol 47, Suppl 1, 2006
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Epilepsia 2006;47(S1):35-40
2. Treiman DM. Generalized convulsive status epilepticus. In: Engel J, Pedley TA
(editors). Epilepsy: a comprehensive textbook. Philadelphia: Lippincott Williams
& Wilkins, 2008. pp 665-73
3. Raspall-Chaure M, Chin RFM, Neville BG, Bedford H, Scott RC. The
epidemiology of convulsive status epilepticus in children: a critical review.
Epilepsia 2007;48(9):1652-1663
4. Chapman MG, Smith M, Hirsch NP. Status epilepticus. Anaesthesia
2001;56:648-659
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