Keywords:
status epilepticus; subclinical status
epilepticus; nonconvulsive status
epilepticus; refractory status
epilepticus; anticonvulsant
Status Epilepticus
in the Pediatric
Emergency
Department
Jonathan E. Kurz, MD, PhD,
Joshua Goldstein, MD
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STATUS EPILEPTICUS IN THE PEDIATRIC EMERGENCY DEPARTMENT / KURZ AND GOLDSTEIN VOL. 16, NO. 1 39
EPIDEMIOLOGY
Status epilepticus is one of the most common
pediatric neurologic emergencies, with an incidence
of 17 to 38 per 100 000 in children. 4,29 The
incidence of pediatric SE is age dependent; reported
incidences are as high as 51 to 156 per 100 000 in
the first year of life 4,29 and lowest among adolescents. Most epidemiologic studies of SE have used a
30-minute time-point as the definition of SE;
including children that present with prolonged
seizures in the 5- to 29-minute range would likely
result in higher incidences. The mean age of
children presenting with SE is 4.4 years. Most of
these cases are convulsive SE. 30
Prior neurologic conditions are a risk factor for
developing SE. Fifty-six to 60% of children presenting with SE are neurologically normal beforehand,
whereas the remainder have a preexisting neurologic abnormality. 4,30 These remote symptomatic
causes of SE are less common in younger children
(who more commonly present with febrile or acute
symptomatic SE) and more common in older
children and adolescents. In one study, 60% of
children older than 5 years with SE had a prior
neurologic abnormality, compared with only 21% of
children younger than 2 years. 30
Preexisting epilepsy is a risk factor for developing
SE. Approximately 10% of children with childhoodonset epilepsy will experience at least one episode
of SE. 31 In an analysis of 2 large cohorts of children
with SE, 45% had a history of one or more
unprovoked afebrile seizures. 30 Among children
with chronic epilepsy, a major risk factor for
developing SE is having experienced prior episodes
of SE; 32 occurrence of SE is more than 20-fold
higher in children with a history of SE than in those
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events are simple febrile seizures, or, single, nonfocal events lasting less than 10 minutes occurring
in otherwise healthy children. However, febrile SE
(defined as duration N 30 minutes) represents 5% of
all febrile seizures, and febrile SE is the underlying
etiology for approximately one quarter of all
episodes of childhood SE. Febrile SE accounts for
more than two thirds of SE occurring in children
between 1 and 2 years of age. 30 These seizures can
be very prolonged; in one study, 24% of episodes of
febrile SE lasted longer than 2 hours. 35 Ninety
percent of patients in febrile SE required an AED to
terminate the seizures, with patients requiring an
average of 2 medications. 36 Most of febrile SE is
convulsive, and most seizures have some focal
features. 35 As with other etiologies of SE, prompt
treatment should be initiated to limit neurologic
morbidity in febrile SE. Prolonged febrile seizure
can lead to acute hippocampal injury detectable on
MRI, with increased risk for the development of
mesial temporal sclerosis. 37 Although common,
febrile SE is a diagnosis of exclusion, and other
causes of prolonged seizure with fever, including
CNS infection, should be excluded. Cerebrospinal
fluid (CSF) analysis in children after febrile SE is
typically normal, 38 and CSF pleocytosis should
raise a concern for CNS infection or another
medical explanation.
Central nervous system infection is a common
etiology of SE in children. Meningoencephalitis or
encephalitis, either bacterial or viral, can lead to SE.
A documented CNS infection was reported on
average in 12.8% of children with SE in one metaanalysis. 39 In a series of 24 children with SE and
fever, bacterial meningitis was detected in 17% of
the febrile group, none of whom exhibited typical
signs of meningismus. 40 Another report documented acute bacterial meningitis in 11% of children
presenting with first ever febrile SE. 4 Given these
data, lumbar puncture (LP) and CNS imaging should
be obtained in the setting of SE and fever at any age,
unless an LP is contraindicated or another etiology
is clearly identified. Empiric treatment with antibiotics and acyclovir should be considered until CSF
analysis excludes herpes encephalitis or bacterial
meningitis as a possibility.
Among children with preexisting epilepsy, medication noncompliance or withdrawal is a frequent
cause of SE. Even children with well-controlled
epilepsy can experience prolonged seizures after
missing medication doses. Among children taking
AEDs who experienced SE, 32% had low serum
levels in one analysis. 39 In children with epilepsy
who are taking AEDs, obtaining serum levels
should be considered if available. A careful
medication history should be obtained to determine if there are missed doses or recent medication changes.
Electrolyte abnormalities such as hyponatremia,
or metabolic abnormalities such as hyperglycemia
or hypoglycemia, can play a role in pediatric SE.
Hypocalcemia may present as SE in neonates. In
studies of the diagnostic yield of these studies,
electrolyte or glucose abnormalities have been
reported in 6% of children with SE on average. 39
Status epilepticus induced by electrolyte abnormalities may be refractory to treatment until the
underlying metabolic disturbance is corrected.
Evaluation of electrolytes and glucose should be
obtained on all children presenting with SE. Toxic
ingestion may be suggested by the history and
should also be considered in cases with unknown
etiology. Toxic ingestion is documented in 3.6% of
reported cases of SE. 39 Serum and urine toxicology
may be helpful in establishing a diagnosis in these
cases. Urine toxicology screening tests typically evaluate only for drugs of abuse; if ingestion of a specific
agent is suggested by the history, specific serum
toxicologic testing for that agent may be more useful.
Seizures and SE can be the presenting symptom
of traumatic brain injury. Although trauma may be
suggested by the history or examination, in some
cases, the history may be unclear. In particular, in
cases of nonaccidental trauma, the initial history
may be incomplete or inaccurate. Nonaccidental
injury in infants is strongly associated with the
development of prolonged seizure activity. 41 Clinicians should be observant for any external findings
that are suggestive of traumatic injury. In cases
where a clear etiology of SE cannot be identified,
neuroimaging should be obtained once the child is
stabilized and the seizures are controlled. These
studies are reasonably high yield in this setting; in
one study of patients with new-onset seizure
presenting as SE, neuroimaging (computed tomography [CT] or MRI) was diagnostic of an underlying
etiology in 30% of patients and directed management
STATUS EPILEPTICUS IN THE PEDIATRIC EMERGENCY DEPARTMENT / KURZ AND GOLDSTEIN VOL. 16, NO. 1 41
ACUTE TREATMENT
Although guidelines and practice parameters
regarding the acute management of SE are available, 9 there is no universally accepted treatment
paradigm for pediatric SE, and protocols can vary
between institutions. 44 Despite this, there is agreement on common principles of treatment of SE,
including the need for rapid and appropriate
therapy to terminate seizures (Figure 1). As with
any critically ill patient, the first steps in management should be assessment of vital signs, airway,
breathing, and circulation. The airway should be
secured, first with noninvasive maneuvers (midline
First-Line Treatment
Intravenous lorazepam is the preferred agent for
initial therapy of SE. Data from adult studies suggest
that IV lorazepam is superior to IV diazepam and IV
phenytoin alone for control of SE, 45 although one
pediatric randomized clinical trial suggests that IV
diazepam and lorazepam may be equivalent in
children. 46 Lorazepam should be given at a dose of
0.1 mg/kg IV (at a rate of up to 2 mg/min) to a
maximum dose of 2 to 4 mg. If IV access is not
available or will require a significant delay in therapy,
numerous other benzodiazepine dosage routes are
available. Midazolam can be administered via intramuscular, buccal, or intranasal routes; buccal or
intranasal dosing is 0.2 to 0.5 mg/kg up to a maximal
dose of 10 mg. 47,48 Diazepam is the preferred
medication for rectal administration. Rectal dosing
ranges from 0.2 to 0.5 mg/kg, depending on age. 49
Benzodiazepine therapy should be provided promptly
and at an adequate dose.
Importantly, frequent small or subtherapeutic doses
of benzodiazepines should be avoided, as this will delay
time to adequate serum concentrations of anticonvulsant. Instead, 1 or 2 doses of benzodiazepine should be
provided at a therapeutic dose, to allow for more timely
administration of a second agent if needed.
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Second-Line Treatments
After initial therapy with benzodiazepines, the next
phase of management is an IV loading dose of an AED.
There are 2 goals of this phase of therapy: terminating
ongoing seizure activity and rapidly producing
therapeutic serum concentrations of an AED for
ongoing seizure control after SE is terminated.
Intravenous fosphenytoin is most commonly used
as the agent of choice for second-line therapy in
pediatric SE. Fosphenytoin is a water-soluble prodrug
that is converted to phenytoin by serum and tissue
alkaline phosphatase within 10 minutes of administration. Phenytoin acts at neuronal voltage-gated
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STATUS EPILEPTICUS IN THE PEDIATRIC EMERGENCY DEPARTMENT / KURZ AND GOLDSTEIN VOL. 16, NO. 1 45
SUMMARY
Status epilepticus is a common neurologic emergency that frequently presents to pediatric emergency providers. Although criteria for the definition
of SE vary, there is agreement that treatment should
begin early in the course of continuous seizures.
Delay in treatment increases the risk of prolonged
seizure, medication unresponsiveness, and potential neuronal injury. Treatment protocols may differ
across institutions, but should share common
principles of rapid treatment with appropriate
doses of AEDs. Initial therapy with a benzodiazepine, followed by a second-line agent (typically
fosphenytoin), should be achieved within the first
20 minutes of SE. The initial diagnostic workup
should occur concurrently and should be focused on
identifying acute symptomatic causes of SE that are
either reversible or impact acute management.
Assessment of glucose and electrolytes should be
obtained, an LP obtained in febrile patients, and
neuroimaging performed in all cases where the
underlying etiology is not immediately apparent.
Patients failing appropriate doses of 2 AEDs have
RSE; further treatment can include additional IV
AEDs and continuous infusions of midazolam or
pentobarbital. Patients with RSE will often require
admission to a pediatric ICU for ongoing treatment.
A high index of suspicion should be maintained
regarding NCSE, particularly in patients that do not
have an improvement in mental status after
treatment of CSE.
Acknowledgments
This work was supported by The Ruth D. & Ken M.
Davee Pediatric Neurocritical Care Program.
Conflict of interest: The authors have no conflicts
of interest to disclose.
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