1110

Status Epilepticus

EBM ALG

BASIC INFORMATION

DEFINITION
Status epilepticus is a medical neurologic emergency. It is historically defined as 30 min of continuous seizure activity or two or more seizures
without full recovery of consciousness between
seizures. However, in practice a continuous
seizure that lasts >5 min should be treated as
status epilepticus.
SYNONYMS
Convulsive status epilepticus
Nonconvulsive status epilepticus
ICD-9CM CODES
345.3Grand mal status
ICD-10CM CODES
G41Status epilepticus
G40.301Generalized idiopathic epilepsy
and epileptic syndromes, not
intractable, with status epilepticus

EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE: 40 to 100 cases per 100,000
persons
PEAK INCIDENCE: It is most common among
children younger than 1 yr and adults older
than 60 yr.
PREDOMINANT SEX AND AGE: No gender
preference
PHYSICAL FINDINGS & CLINICAL
PRESENTATION


Patients can present with repetitive tonic
clonic movements of the body (convulsive
status epilepticus); other patients are comatose and nonresponsive (nonconvulsive status epilepticus).


Patients may also present with lethargy,
intermittent confusion, and involuntary
movements.
ETIOLOGY
Status epilepticus can be the result of an
acute neurologic injury, such as stroke, meningitis, etc.
In patients with epilepsy, abrupt discontinuation of antiepileptic drugs can result in status
epilepticus.
See Table 1-459 for causes of status epilepticus.
TABLE 1-459 Causes of
Status Epilepticus
Stroke (ischemic/hemorrhagic)
CNS infections
Traumatic head injury
CNS toxicity: certain medications, drugs, ethanol
Brain tumors or other mass lesions
Metabolic disturbances: hypoglycemia, hyponatremia
Abrupt discontinuation of antiepileptic drugs in
patient with epilepsy
Cryptogenic
CNS, Central nervous system.

Dx DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
Convulsive syncope
Encephalopathies: metabolic, infectious, toxic,
etc.
Nonepileptic spells
WORKUP
ABCs
ICU admission
Emergent electroencephalogram (EEG)
Continuous video EEG in refractory cases
Investigation of the patient with status epilepticus is summarized in Box 1-81.
LABORATORY TESTS
Routine blood workup (CBC, CMP, glucose,
electrolytes)
Urine drug screen
Lumbar puncture and CSF analysis in patients
with suspected meningitis

IMAGING STUDIES
Immediate CT scan of the head
MRI of the brain should be performed once
the patient is in a stable condition.

Rx TREATMENT
Patients with continuous seizure activity over
3 min need intravenous lorazepam 0.1 mg/kg
at 2 mg/min (or diazepam 0.2 mg/kg at 5 mg/
min only when lorazepam is not available).
Lorazepam is followed by intravenous fosphenytoin 20 mg/kg (PE) at a rate not greater
than 150 mg/min.
An alternate to fosphenytoin is phenytoin 20
mg/kg IV at up to 50 mg/min as tolerated. Vital
signs should be monitored during the infusion.
If seizures continue, intravenous phenobarbital, midazolam, or propofol is an alternative. Other agents used include intravenous
valproic acid and intravenous levetiracetam.
Results of recent trials comparing intramuscular midazolam vs. intravenous lorazepam
for prehospital status epilepticus show that
IM midazolam may be as good as lorazepam,

BOX 1-81Investigation of the Patient with Status Epilepticus

To Be Performed in All Patients with Status Epilepticus
Serum glucose, electrolytes, calcium, magnesium
Blood gas, serum osmolality
Toxicology screen (serum and urine)
Antiepileptic drug levels
Complete blood count (RBC, differential WBC, platelet count)
Liver enzymes, serum ammonium
Blood culture
Lumbar puncture, including:
C Opening pressure
C Cell count, Gram stain, smear for acid-fast bacilli
C Viral and bacterial cultures
C PCR for herpesvirus
EEG, preferably continuous monitoring with video
C To monitor for subtle or subclinical seizures
C To guide antiepileptic drug therapy
C To localize the epileptogenic brain region (focal slowing or epileptiform activity)
To Be Considered in Patients with Status Epilepticus
Structural neuroimaging (CT, MRI)
C To diagnose acute infarction, hemorrhage, vascular malformation, encephalitis,
abscess, neurocysticercosis, neoplasm
C In nonlesional cases, may localize the epileptogenic zone by evidence of focal
edema in the affected cortical region
C To assess the degree of cerebral edema and diagnose impending uncal or transtentorial herniation
C MR angiography may identify CNS vasculitis, especially in medium or large vessel
disease
Functional neuroimaging (PET, SPECT)
C In nonlesional cases, may identify the epileptogenic zone
Cerebral angiography
C To identify small vessel CNS vasculitis, which may not be visible on MR angiography
Rheumatologic workup for vasculitides
ESR, C-reactive protein, rheumatoid factor, serum complement levels, antineutrophil
cytoplasmic antibodies
Brain biopsy
C To diagnose cerebral vasculitis (granulomatous compared with nongranulomatous)
C To identify malformations of cortical development
CNS, Central nervous system; CT, computed tomography; EEG, electroencephalography; ESR, erythrocyte
sedimentation rate; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PET, positron emission tomography; RBC, red blood cell; SPECT, single-photon emission computed tomography; WBC, white
blood cell.
From Fuhrman BP etal: Pediatric critical care, ed 4, Philadelphia, 2011, Saunders.

EBM ALG


COMPLEMENTARY &
ALTERNATIVE MEDICINE
Not applicable

NONPHARMACOLOGIC THERAPY
None

REFERRAL
Status epilepticus is a neurologic emergency;
therefore immediate neurologic consultation is
warranted.

GENERAL Rx
It is important to find out the etiology of the
status epilepticus (e.g., metabolic disturbance, infection). The appropriate treatment/
understanding of the underlying cause of
the status epilepticus will impact successful
treatment.
CHRONIC Rx


Chronic treatment of status epilepticus
depends on underlying etiology.
Patient with status epilepticus due to epilepsy will need chronic treatment.

Patient in GCSE,
NCSE, CPSE

DISPOSITION
Response to treatment depends on the etiology of the status epilepticus.
When there is no CNS injury as a cause or
result of the status epilepticus, the prognosis
is good.
No driving until seizure freedom in accordance with local laws and regulations.

PEARLS &
CONSIDERATIONS

COMMENTS


Status epilepticus is a medical emergency
that carries a high risk of mortality. Mortality
among patients who present in status epilepticus is 15% to 22%. Among those who survive,
functional ability will decline in 25% of cases.
Continuous video EEG is crucial in the treatment of these patients because some of

them may not be clinically seizing (convulsing) but electrographically they may still have
subclinical repetitive seizures or subclinical
status epilepticus.

Glucose, 1 mg/kg, and

thiamine, 1 mg/kg
Seizures persist
Lorazepam 0.1 mg/kg
Seizures persist
Phenytoin or
fosphenytoin 20 mg/kg

Seizures
stop

PATIENT & FAMILY EDUCATION

Patients with epilepsy have normal lives.
The goal of treatment is no seizures and no
side effects to medications.


Patient education and information can be
obtained at the Epilepsy Foundation: www.
epilepsyfoundation.org
Pregnant women with epilepsy should visit
the Antiepileptic Drug Pregnancy Registry
website for information and assistance: www
2.massgeneral.org/aed
Patients with ongoing seizures are forbidden
from driving; check state regulations and
laws regarding driving and epilepsy.
SUGGESTED READINGS
available at www.expertconsult.com
AUTHOR: PATRICIO SEBASTIAN ESPINOSA,
M.D., M.P.H.

Seizures
stop

Seizures persist
High-dose barbiturates
(see text)

Observe
patient

Patient begins
to arouse

Prevent recurrence
of SE and manage
underlying causes

Seizures
stop

Seizures persist
Midazolam 0.2 mg/kg
then 0.12.0 mg/kg/hr
or
Propofol 3 mg/kg then
115 mg/kg/hr

Work up
and manage
hypoglycemia

Observe
patient

Seizures
stop

Seizures
stop

PREVENTION
Medication compliance is crucial in patients
with epilepsy.

Patient not beginning

to arouse 15 min after
apparent end of seizure

Airway, breathing,
circulation

1111

Patient does not

begin to arouse
within 15 min

Obtain emergent EEG monitoring;

assume that the patient is in
NCSE until proven otherwise

FIGURE 1-885 Management algorithm for status epilepticus. CPSE, Complex partial status epilepticus;
GSCE, generalized convulsive status epilepticus; NCSE, nonconvulsive status epilepticus; SE, status epilepticus.
(From Vincent JL etal: Textbook of critical care, ed 6, Philadelphia, 2011, Saunders.)

Diseases
and Disorders

with successful termination of seizures in

73% of patients in the IM midazolam group
vs. 63% in the IV lorazepam group. This
difference was attributed to the more rapid
administration of the IM medication (1.2 min
vs. 4.8 min with the IV route).
A management algorithm for status epilepticus in adults is described in Fig. 1-885.
Fig. E1-886 describes guidelines for the
treatment of prolonged seizures and status
epilepticus in infants (>1 mo), children, and
adolescents and refractory status epilepticus.

Status Epilepticus

Status Epilepticus
EVIDENCE
A 54-year-old woman was transferred to a university hospital for severe
sepsis and multiorgan failure. A complex partial seizure was noted and
she was placed on continuous electroencephalography (EEG). During
EEG monitoring she developed generalized convulsive status epilepticus.
After consultation with family it was decided not to escalate treatment
due to her overall medical condition. She proceeded sequentially through
the five stages of status epilepticus, described by Treiman etal. (1990)
over 22 h and 30 min and then developed electrocerebral silence. This
case is significant in that it is the first report of a single individual experiencing all five stages of status epilepticus displayed on a continuous
EEG. The case further demonstrates the rapid progression of status epilepticus and exemplifies the need for prompt treatment. A
Evidence-Based Reference
Pender RA, Losey TE: A rapid course through the five electrographic stages of
status epilepticus, Epilepsia 53:e193-e195, 2012. A

1111.e1

SUGGESTED READINGS
Continuum (Minneap Minn) 16(3 Epilepsy), 2010
Hirsh LJ: Intramuscular vs. intravenous benzodiazepines for prehospital treatment
of status epilepticus, N Engl J Med 366:659-661, 2012.
Milligan TA etal: Frequency and patterns of MRI abnormalities due to status
epilepticus, Seizure 18(2):104-108, 2009.
Silbergleit R etal: Intramuscular vs. intravenous therapy for prehospital status
epilepticus, N Engl J Med 366:591, 2012.
Treiman DM etal: A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group,, N
Engl J Med 339(12):792-798, 1998.
Wyllie E etal: The treatment of epilepsy: principles & practice, ed 4, Philadelphia,
2006, Lippincott Williams & Wilkins.

Status Epilepticus

1111.e2

A. Prolonged Seizures and Status Epilepticus

in Infants (Age 1 Month), Children, and Adolescents
Seizure onset
Support ABCs and give oxygen
Attach cardiac and O2 saturation monitors; establish IV access
Rapid glucose check and consider critical labs (Na, Ca, Mg, etc.)
Proceed with the following algorithm until seizures stop
Monitor closely for loss of airway reflexes and respiratory
depression, hypotension, or cardiac arrhythmias.
5 minutes
OR
Lorazepam
IV: 0.1 mg/kg
PR: 0.1 mg/kg
IV/PR max: 4 mg/
dose

OR
Diazepam
IV: 0.3 mg/kg
PR: 0.5 mg/kg
IV max: 5 yrs: 5 mg/dose
5 yrs: 10 mg/dose
PR max: 20 mg/dose

Midazolam
Intranasal: 0.2 mg/kg
Buccal: 0.5 mg/kg
IN max: 5 mg (1 ml)/nostril
Buccal max: 10 mg (2 ml)

5 minutes
Repeat above step
5 minutes
IV access
Fosphenytoin
IV: 20 mg phenytoin
Equivalents (PE)/kg in NS
or D5W over 5-10 min
Max: 1000 mg PE
If fosphenytoin not available,
use phenytoin
IV: 20 mg/kg in NS only over
20 minutes
Max: 1000 mg
5 minutes
Phenobarbital
IV: 20 mg/kg in NS or
D5W over 20 minutes
or IV push by MD over
5-10 min
Max: 1000 mg

No IV access
Phenobarbital
IV: 20 mg/kg in NS or
D5W over 20 minutes
or IV push by MD over
5-10 min
Max: 1000 mg
5 minutes

Fosphenytoin
IV: 20 mg phenytoin
Equivalents (PE)/kg in NS
or D5W over 5-10 min
Max: 1000 mg PE
If fosphenytoin not available,
use phenytoin
IV: 20 mg/kg in NS only over
20 minutes
Max: 1000 mg

10 minutes
Refractory Status Epilepticus
Call CCRT/ICU consult and neurology consult
Call Code Blue if intubation is needed
Request continuous EEG monitoring
Obtain arterial and central venous lines
Arrange admission to ICU

Continue attempts to establish

IV access. Once IV access is
established, proceed according
to IV access protocol
Fosphenytoin
IM: 20 mg phenytoin
Equivalents (PE)/kg
Max: 1000 mg PE
Max dose per IM site: 3 ml
If child 30 kg, IM dosing may
not be practical because of
large dose volume, requiring
multiple IM sites.
5 minutes
Paraldehyde
PR: 400 mg (0.4 ml)/
kg/dose
Max: 10 g (10 ml)/dose
Give diluted 1:1 in
cooking oil (preferred)
or normal saline
10 minutes

Refer to Refractory Status Epilepticus

Guidelines in part B.

FIGURE E1-886 Guidelines for the treatment of prolonged seizures and status epilepticus in infants
(age >1 month), children, and adolescents. (From The Hospital for Sick Children, Toronto, Canada. In
Fuhrman BP etal: Pediatric critical care, ed 4, Philadelphia, 2011, Saunders.)

Status Epilepticus

1111.e3
B. Refractory Status Epilepticus
in Infants (Age 1 Month), Children, and Adolescents
Call CCRT/ICU consult and Neurology consult
Call Code Blue if intubation is needed
Request continuous EEG monitoring
Arrange admission to ICU

Midazolam continuous infusion

IV: 0.15 mg/kg bolus then 2 g/kg/min infusion
Increase as needed by 2 g/kg/min q5 minutes
Bolus 0.15 mg/kg with each increase in the infusion rate
Max infusion rate: 24 g/kg/min
Establish goals of therapy with guidance from
Neurology and Critical Care
Maintain phenobarbital and phenytoin at
therapeutic serum levels with maintenance doses
If seizures persist
Thiopental continuous infusion via CVL
CVL: 2-4 mg/kg bolus then 2-4 mg/kg/hr
Increase as needed by 1 mg/kg/hr every 30 minutes
Bolus 2 mg/kg with each increase in the infusion rate
Max infusion rate: 6 mg/kg/hr
Establish goals of therapy with guidance from
Neurology and Critical Care
Discontinue midazolam and phenobarbital
Maintain phenytoin at therapeutic serum levels
Monitor thiopental levels
If seizures persist

If no
seizures
for 48 hours

Taper midazolam
Decrease by
1 g/kg/min q15 min

If seizures recur, reinstate

midazolam for another 48 hours

If no
seizures
for 48 hours

If seizures recur

Individualized therapy
in consultation with Critical Care and Neurology

FIGURE E1-886 (Continued)

Taper thiopental
Decrease rate by
25% q3 hours
Reinstitute phenobarbital
while tapering