Epilepsia, 48(Suppl.

8):99102, 2007
doi: 10.1111/j.1528-1167.2007.01364.x

OUTCOMES OF STATUS EPILEPTICUS

Status epilepticus treatment guidelines

Reetta Kalviainen
Department of Neurology, Kuopio Epilepsy Center, Kuopio University Hospital, Kuopio, Finland

Status epilepticus (SE) is an underrecognized medical

emergency that requires rapid and aggressive treatment
to prevent neuronal damage, systemic complications, and
death. The incidence of SE is 20 per 100,000 person years
(DeLorenzo et al., 1996; Knake et al., 2001; Metsaranta
et al., 2004). Mortality still remains approximately 20%
and the risk of cognitive decline and development of
epilepsy are increased (DeLorenzo et al., 1996; Knake
et al., 2001; Metsaranta et al., 2004). Standardized guidelines are believed to improve the quality of emergency care
and outcome.

in maximal mg/kg doses, and consider EEG when the diagnosis of nonconvulsive or subtle SE must be excluded.
They stated that both clinical and electrical seizure activity must be stopped quickly to optimize outcome. The
longer the SE endures, the more difficult it is to control and
CNS injury is more likely. Thus, treating early and aggressively was the recommended approach. EFA-guideline was
launched with impressive educational program including
article with reprints and a slide set for the use of educators
worldwide.
Guideline for treating convulsive status epilepticus
in children
The Status Epilepticus Working Party (Appleton et al.,
2000) published a widely cited four-step guideline which
was based on a comprehensive computer based literature
search and consequent consensus statement by the group.

H ISTORY OF THE STATUS

EPILEPTICUS GUIDELINES
Guidelines for phenytoin infusion
The treatment of SE in the 1970s involved administering
1,000 mg of phenytoin, regardless of body weight, at no
specified rate, and without guidelines for monitoring this
infusion. During this time period, mortality from SE surpassed 50%, partially because of unmonitored intravenous
infusion rates. A classical clinical study with intravenous
phenytoin (Cranford et al., 1978) set the standards for monitoring blood pressure and electrocardiograms during SE
treatment, demonstrated that phenytoin infusions should be
no faster than 50 mg/min and in general a dose of 18 mg/kg
was needed.

National status epilepticus guidelines

The National Institute for Health and Clinical Excellence (NICE)-guideline form UK (2004), the Scottish Intercollegiate Guidelines Network (SIGN)-guideline from
Scotland (2003), and guidelines of the Italian League
Against Epilepsy (Minicucci et al., 2006) are examples of
national guidelines. The Finnish Evidence Based Guidelines for Prolonged Seizure and Status Epilepticus (2005)
tries to integrate the treatment of SE to the first aid given
by nonmedical personnel in the premonitory phases of
SE (Table 1, use of phenytoin added to Finnish guidelines).

EFA-guideline 1993
Until late 1980s there was large variation in patient stabilization procedures, laboratory measures, and sequence of
medications in the management of SE. In the year 1993,
the Epilepsy Foundation of America convened a working group on SE. They published guidelines and a treatment protocol (EFA Working Group on Status Epilepticus, 1993), which was based on a literature review and
input from expert reviewers and a professional advisory
board. Some key treatment principles of this guideline
still remain valid: utilize an agreed-upon treatment protocol, serially provide antiepileptic drugs (AEDs) quickly

EFNS-guideline 2006
Last comprehensive guideline for SE was published
by the European Federation of Neurological Societies
(EFNS) (Meierkord et al., 2006). Recommendations
are based on literature search and group discussions
(informative consensus approach). Where there was a lack
of evidence but consensus was clear, the group has stated
its opinion as good practice points (GPP).

D O THE GUIDELINES CHANGE

CLINICAL PRACTICE ?

Address correspondence and reprint requests to Dr. Reetta Kalviainen,

Kuopio Epilepsy Center, Department of Neurology, Kuopio University Hospital, POB 1777, 70211 Kuopio, Finland. E-mail:
Reetta.Kalviainen@kuh.fi

Guidelines for the management of SE have been in the

literature for many years, yet retrospective studies have
confirmed that management often fails to reflect these
guidelines (Walker et al., 1996; Salmenpera et al., 2000;

Blackwell Publishing, Inc.

International League Against Epilepsy


C

99

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R. Kalviainen
TABLE 1.

Protocol for drug treatment, general measures, and emergency investigations of convulsive
status epilepticus as function of time from the onset of the seizure
Prolonged epileptic seizure
Premonitory stage/out-of-hospital (nonmedical persons)
Drug treatment

Time
5 min.

General measures
Adults
Diazepam 10 mg rectally

Children
Diazepam 0.5 mg/kg rectally

Repeat once if necessary

If seizure continues, proceed
Early status epilepticus

Airway
Breathing
Circulation
Safety

Emergency
investigations

Glucometer

First stage/out-of or in-hospital (medical personel)

Time
5 20 min.

Drug treatment
Adults
Lorazepam i.v. 4 mg bolus or

Children
Lorazepam i.v. 0.1 mg/kg (max 4 mg) or

Diazepam i.v. 10 mg

Diazepam i.v. 0.3 mg/kg (max 10 mg)

General measures

Emergency
investigations

Airway; oxygen

Glucose, Na, K, Ca,

CRP, Astrup
Levels of AEDs
Toxicology screening
Kidney and liver
function tests

Cardiorespiratory function
and regular monitoring;
ECG, blood pressure,
SpO 2
Intravenous access; i.v.
glucose, thiamine,
pyridoxine (children)
Treat acidosis

If seizure continues, proceed

Established status epilepticus
Second stage/emergency department
Time
2060 min

Drug treatment
Fosphenytoin i.v. 1518 mg PE/kg at max. rate of 150 mg PE/min or
Phenytoin i.v. 1518 mg/kg at max. rate of 50 mg/min

or in children: Phenobarbital i.v. 1520 mg/kg at max. rate of 100 mg/min

General measures
Cardiorespiratory function
and monitoring;
ECG, blood pressure,
SpO2, use pressors if
needed
Identify and treat medical
complications

Emergency
investigations
CT scan for etiology
CSF for CNS infection

EEG for pseudostatus

If seizure continues, proceed

Refractory status epilepticus
Third stage/intensive care unit
Time

Drug treatment

>60 min

General anesthesia

Thiopental; 35 mg/kg bolus, then 35 mg/kg/h or

Pentobarbital 1015 mg/kg, then 0.51 mg/kg/h

or
Midazolam; 0,2 mg/kg boluses max. 2 mg/kg, then 0.052 mg/kg/h
or only in adults:
Propofol; 12 mg/kg boluses, max. 10 mg/kg, then 210 mg/kg/h
PE, phenytoin equivalents; SpO 2 , pulse oximetry. Modified from Finnish guideline.

Epilepsia, 48(Suppl. 8):99102, 2007

doi: 10.1111/j.1528-1167.2007.01364.x

General measures
Intensive care; ventilatory
and hemodynamic
treatment

Increased intracranial
pressure; measure and
treat if signs
Anesthesia continued for
1224 h after last clinical
or electrographic seizure
Optimize maintenance
AED treatment

Emergency
investigations
Continuous EEG
monitoring;
electrographic
seizures, depth of
anesthesia
(burst-suppression)
Monitor

Astrup, K, Na, glucose,

lactate, levels of
AEDs

101
SE Treatment Guidelines
Cascino et al., 2001; Cock and Schapira, 2002). SIGNguidelines have been studied in general to determine the effectiveness implementation strategies (Davis et al., 2004).
None of the intervention strategies led to improvements in
patient quality of life or quality of epilepsy care. The problems of guideline implementation in medicine in general
are recognized and documented both within hospital (Marshall et al., 1999; Costantini et al., 2001) and community
practice (Loeb et al., 2001).

R EASONS FOR FAILURE TO

IMPLEMENT GUIDELINES
There have been few systematic studies of factors contributing to poor guideline adherence, but a variety of
barriers to guideline implementation are recognized in
the emergency setting. The key reason for the lack of
implementation of the SIGN epilepsy guideline was an
established pattern of staff behavior, with which there was
little perceived need to change (Williams et al., 2007). Secondary to this there was lack of knowledge of the existence
and/or content of the guideline and perceived difficulties in
implementing them in clinical practice stemming from resource constraints. Moreover, the high turnover of treating
(largely junior) medical staff in emergency units requires
very regular reinforcement of guidelines if they are to be
maintained (Cock and Schapira, 2002).

W HAT IS NEEDED?
The implementation of evidence based medicine finds
its most receptive ground when there are local opinion
leaders who are supportive, there is accessibility through
user friendly information technology, and the guidelines
are focused and dictate specific actions. However, recent
findings from implementation studies show that guidelines
may not be even looked at if they are regarded as unnecessary. On the other hand guidelines are more likely to
be implemented where there are perceived problems with
current service delivery. Therefore, it is necessary to take
that a feedback system is in place at participating levels of
care and they have to participate in gathering the evidence
supporting the need for the guidelines. Clinical scenarios
should be examined and followed for noncompliance of
the guideline and the guidelines should be corrected accordingly if practice shows better ways of doing things.
Secondly, as treating early and aggressively is the recommended approach, it is critical to start the protocols
from home and public education and from the prehospital setting, not from the hospital and integrate all parts of
the critical treatment pathway.
Prehospital emergency response systems must train
personnel to correctly identify patients with prolonged
seizures and SE and work closely with hospital emergency

departments to transport these patients rapidly to appropriate centers.

Emergency departments must have specialized protocols
in place for identifying SE patients and treating those who
require therapy within a narrow therapeutic time window.
Response systems, including optimal time frames, must be
established, maintained, and monitored in all emergency
departments.
Hospitals must develop local status epilepticus guidelines and protocols that define the specialized roles of nursing staffs, diagnostic units, neurological and intensive care
teams, and other treatment services such as pharmacy and
rehabilitation.
Public education is critically important in ensuring that
all of the efforts cited above are successful. The public
must learn that a prolonged seizure is a medical emergency,
that a treatment is now available, and that this treatment is
only effective when given rapidly after the onset of symptoms. Lay people programs and first responder programs
with police officers, etc. are very important. These should
include protocol guidelines for the first aid management
of epileptic seizures, including the advice when to call
ambulance.

C ONCLUSION
Morbidity and mortality in SE increase with prolonged
seizure activity. Early and aggressive intervention is the
hallmark of successful treatment of SE. Guidelines need to
be developed for pathways from home to intensive care unit
and we need to raise the awareness of the current problems
like that of treatment delay and motivate the community to
implement the guidelines to overcome problems.

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