Epilepsia, 48(Suppl.
8):99–102, 2007
doi: 10.1111/j.1528-1167.2007.01364.x
OUTCOMES OF STATUS EPILEPTICUS
Status epilepticus treatment guidelines
Reetta Kälviäinen
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; Metsäranta
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; Metsäranta et al., 2004). Standardized guide-
lines are believed to improve the quality of emergency care
and outcome.
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 sur-
passed 50%, partially because of unmonitored intravenous
infusion rates. A classical clinical study with intravenous
phenytoin (Cranford et al., 1978) set the standards for mon-
itoring 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.
EFA-guideline 1993
Until late 1980s there was large variation in patient stabi-
lization procedures, laboratory measures, and sequence of
medications in the management of SE. In the year 1993,
the Epilepsy Foundation of America convened a work-
ing group on SE. They published guidelines and a treat-
ment protocol (EFA Working Group on Status Epilepti-
cus, 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 pro-
tocol, serially provide antiepileptic drugs (AEDs) quickly
Address correspondence and reprint requests to Dr. Reetta Kälviäinen,
Kuopio Epilepsy Center, Department of Neurology, Kuopio Uni-
versity Hospital, POB 1777, 70211 Kuopio, Finland. E-mail:
Reetta.Kalviainen@kuh.fi
Blackwell Publishing, Inc.

C International League Against Epilepsy
99
in maximal mg/kg doses, and consider EEG when the di-
agnosis of nonconvulsive or subtle SE must be excluded.
They stated that both clinical and electrical seizure ac-
tivity 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 aggres-
sively 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.
National status epilepticus guidelines
The National Institute for Health and Clinical Exce-
llence (NICE)-guideline form UK (2004), the Scottish In-
tercollegiate 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 Guide-
lines 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 guide-
lines).
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 ?
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; Salmenperä et al., 2000;
100

R. Kälviäinen

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
Emergency
Time General measures investigations
5 min. Adults Children
Diazepam 10 mg rectally Diazepam 0.5 mg/kg rectally Airway
Breathing Glucometer
Circulation
Repeat once if necessary Safety
If seizure continues, proceed
Early status epilepticus

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

Time Drug treatment General measures Emergency
investigations
5 – 20 min. Adults Children
Lorazepam i.v. 4 mg bolus or Lorazepam i.v. 0.1 mg/kg (max 4 mg) or Airway; oxygen Glucose, Na, K, Ca,
CRP, Astrup
Diazepam i.v. 10 mg Diazepam i.v. 0.3 mg/kg (max 10 mg) Cardiorespiratory function Levels of AEDs
and regular monitoring; Toxicology screening
ECG, blood pressure, Kidney and liver
SpO 2 function tests
Intravenous access; i.v.
glucose, thiamine,
pyridoxine (children)
Treat acidosis
If seizure continues, proceed
Established status epilepticus
Second stage/emergency department
Time Drug treatment General measures Emergency
investigations
20–60 min Fosphenytoin i.v. 15–18 mg PE/kg at max. rate of 150 mg PE/min or Cardiorespiratory function CT scan for etiology
and monitoring;
Phenytoin i.v. 15–18 mg/kg at max. rate of 50 mg/min ECG, blood pressure, CSF for CNS infection
SpO2, use pressors if
needed
or in children: Phenobarbital i.v. 15–20 mg/kg at max. rate of 100 mg/min Identify and treat medical EEG for pseudostatus
complications
If seizure continues, proceed
Refractory status epilepticus
Third stage/intensive care unit
Time Drug treatment General measures Emergency
investigations
>60 min General anesthesia Intensive care; ventilatory Continuous EEG
and hemodynamic monitoring;
treatment electrographic
seizures, depth of
anesthesia
(burst-suppression)
Thiopental; 3–5 mg/kg bolus, then 3–5 mg/kg/h or Increased intracranial Monitor
pressure; measure and
treat if signs
Pentobarbital 10–15 mg/kg, then 0.5–1 mg/kg/h Anesthesia continued for Astrup, K, Na, glucose,
12–24 h after last clinical lactate, levels of
or electrographic seizure AEDs
or Optimize maintenance
AED treatment
Midazolam; 0,2 mg/kg boluses max. 2 mg/kg, then 0.05–2 mg/kg/h
or only in adults:
Propofol; 1–2 mg/kg boluses, max. 10 mg/kg, then 2–10 mg/kg/h

PE, phenytoin equivalents; SpO 2 , pulse oximetry. Modified from Finnish guideline.

Epilepsia, 48(Suppl. 8):99–102, 2007

doi: 10.1111/j.1528-1167.2007.01364.x

Cascino et al., 2001; Cock and Schapira, 2002). SIGN-
guidelines have been studied in general to determine the ef-
fectiveness 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 prob-
lems of guideline implementation in medicine in general
are recognized and documented both within hospital (Mar-
shall 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 con-
tributing 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). Sec-
ondary 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 re-
source 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 unnec-
essary. 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 ac-
cordingly if practice shows better ways of doing things.
Secondly, as treating early and aggressively is the rec-
ommended approach, it is critical to start the protocols
from home and public education and from the prehospi-
tal 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
101
SE Treatment Guidelines
departments to transport these patients rapidly to appropri-
ate 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 guide-
lines and protocols that define the specialized roles of nurs-
ing 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 symp-
toms. 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.
R EFERENCES
Appleton R, Choonara I, Martland T, Phillips B, Scott R, Whitehouse W.
(2000) The treatment of convulsive status epilepticus in children. Arch
Dis Childhood 83:415–419.
Cascino GD, Hesdorffer D, Logroscino G, Hauser WA. (2001) Treatment
of nonfebrile status epilepticus in Rochester, Minnesota, from 1965
through 1984. Mayo Clin Proc 76:39–41.
Cock H, Schapira A. (2002) A comparison of lorazepam and diazepam as
initial therapy in convulsive status epilepticus. Q J Med 95:225–231.
Costantini O, Huck K, Carlson MD, Boyd K, Buchter CM, Raiz P, Cooper
GS. (2001) Impact of a guideline-based disease management team on
outcomes of hospitalized patients with congestive heart failure. Arch
Intern Med 161:177–182.
Cranford RE, Leppik IE, Patrick B, Anderson CB, Kostick B. (1978) In-
travenous phenytoin: clinical and pharmacokinetic aspects. Neurology
28:874–880.
Davis JPL, Roberst RC, Davidson DLW, Norman A, Ogson S, Grimshaw
JM, Davey P, Grant J, Ruta D. (2004) Implementation strategies for
a Scotiish epilepsy guidelines in primary care: results of a Tayside
Implementation of Guidelines in Epilepsy Randomised (TIDER) trial.
Epilepsia 45:28–34.
DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy
L, Gartnett L, Fortner D, Ko D. (1996) A prospective, population-
based epidemiologic study of status epilepticus in Richmond, Vir-
ginia. Neurology 46:1029–1035.
Epilepsia, 48(Suppl. 8):99–102, 2007
doi: 10.1111/j.1528-1167.2007.01364.x
102
R. Kälviäinen
EFA Working Group on Status Epilepticus. (1993) Treatment of convul-
sive status epilepticus. Recommendations of the Epilepsy Foundation
of America’s Working Group on status epilepticus. JAMA 270:854–
859
Finnish national guidelines for the treatment of prolonged seizures and
status epilepticus. (2005) Summary by Kälviäinen R in English. In
Evidence-Based Medicine Guidelines by Duodecim Medical Publi-
cations Editor-in-Chief Kunnamo I. Wiley, Cichester, West Sussex,
England. Full text in Finnish in http://www.kaypahoito.fi (accessed
October 15, 2007).
Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A,
Katsarou N, Hamer HM and the Status Epilepticus Group Hessen
(SESGH). (2001) Incidence of status epilepticus in adults in Germany:
a prospective, population-based study. Epilepsia 42:714–718.
Loeb M, Simor AE, Landry L, McGeer A. (2001) Adherence to antibiotic
guidelines for pneumonia in chronic-care facilities in Ontario. Clin
Invest Med 24:304–310.
Marshall C, Ramaswamy P, Bergin FG, Rosenberg IL, Leaper DJ. (1999)
Evaluation of a protocol for the non-operative management of perfo-
rated peptic ulcer. Br J Surg 86:131–134.
Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P,
Holtkamp M. (2006) EFNS guideline on the management of status
epilepticus. Eur J Neurol 13:445–450.
Epilepsia, 48(Suppl. 8):99–102, 2007
doi: 10.1111/j.1528-1167.2007.01364.x
Metsäranta P, Koivikko M, Peltola J, Eriksson K. (2004) Outcome af-
ter prolonged convulsive seizures in 186 children: low morbidity, no
mortality. Dev Med Child Neurol 46:4–8.
Minicucci F, Muscas G, Perucca E, Capovilla G, Vigevano F, Tinu-
per P. (2006) Treatment of status epilepticus in adults: guidelines
of the Italian league against epilepsy. Epilepsia 47(Suppl. 5):9–
15.
NICE guideline Epilepsy. (2004) www.nice.org.uk/CG020 (accessed
October 15, 2007).
Salmenperä T, Kälviäinen R, Partanen K, Mervaala E, Pitkänen A. (2000)
MRI volumetry of the hippocampus, amygdala, entorhinal cortex,
and perirhinal cortex after status epilepticus. Epilepsy Res 40:155–
170.
SIGN guideline Diagnosis and Managemnet of Epilepsy in Adults
(2003) www.sign.ac.uk/pdf/sign70.pdf (accessed October 15,
2007).
Walker MC, Howard RS, Smith SJ, Miller DH, Shorvon SD, Hirsch NP.
(1996) Diagnosis and treatment of status epilepticus on a neurological
intensive care unit. Q J Med 89:913–920.
Williams B, Skinner J, Dowell J, Roberts R, Crombie I, Davis J. (2007)
General Practitioners’ Reasons for the Failure of a Randomized Con-
trolled Trial (The TIGER Trial) to Implement Epilepsy Guidelines in
Primary Care. Epilepsia 48:1275–1282.