|
Introduction References Annotated Bibliography Questions Pediatric
Seizures and Status Epilepticus (SE):
Case Presentation This presentation addresses the following topics related to pediatric seizure and status epilepticus: 1) Pre-hospital treatment 2) Emergency department treatment 3) Rapid and effective diagnosis, treatment, and disposition of patients
Introduction
This document addresses pediatric seizures and SE as
they relate to pre-hospital providers and the staff in the Emergency
department. The goal
of this information is to facilitate the rapid and effective diagnosis,
treatment, and disposition of pediatric patients with seizures and
SE.
Overall Seizure Epidemiology There
are an estimated 2.5 million patients with epilepsy in the United
States, a prevalence of about 6.6 per 1000 Americans.
Up to 28% of these epilepsy patients are treated in the Emergency
Department annually. Status
epilepticus (SE) occurs in 50-150,000 patients per year, with a mortality
of 22%.
The incidence of SE is 50 per 100,000 Americans, with the greatest
incidence being at the extremes of age.
Status epilepticus is seen in up to 7% of Emergency Department
seizure patients, and most emergency physicians report treating five
or more cases of SE per year.
The etiology of SE in the Emergency Department is similar to that
of all emergency seizure patients, with alcohol, drugs, or low anti-epileptic
drug (AED) levels causing more than 50% of SE episodes treated.
Pediatric Seizure Epidemiology and Etiology The
CNS of children is more immature, making children more likely to seize
but also more refractory to the consequences of an acute seizure or
SE. SE is most common
in children younger than one year of age, and in children who develop
SE, 50% will do so in the first year of their life.
The most common causes of SE in children are fever, CNS infection,
and epilepsy, accounting for over 75% of SE episodes in children less
than one year of age. Other
etiologies of SE in children include hyponatremia, inadvertent ingestions
of cocaine or other toxins, and structural CNS abnormalities.
The outcome of children with SE depends on the CNS status of
the child prior to the onset of the SE, the better outcomes associated
with children without underlying CNS abnormalities.
The 3-6% mortality seen in pediatric SE most often is related
to an acute neurologic insult or a chronic CNS condition. In
two studies from an urban ED, up to one percent of all patients seen
in the ED were noted to be pediatric seizure patients.
Febrile seizures were noted to comprise 80% of these patients,
with only 20% of pediatric patients presenting with afebrile seizures.
Febrile seizures are commonly seen in the emergency department
because they occur in 2-5% of all children.
By definition, simple febrile seizures are brief (lasting less
than 15 min duration), generalized, and non-recurrent.
Given the more aggressive definition of SE being used today,
it is reasonable to consider children whose febrile seizures last
for greater than 5-10 minutes to be complex, and diagnose the patient
as having SE.
Seizure
Classification Pediatric
seizures can be broadly classified into generalized and partial seizures.
Generalized seizures involve both cerebral hemispheres, while
partial seizures involve only one cerebral hemisphere.
Generalized seizures either are convulsive (generalized tonic-clonic
seizures) or non-convulsive (absence seizures).
Partial seizures are either simple, in that they do not involve
an alteration in consciousness, or complex, when there is impaired
consciousness. Simple
partial seizures manifest themselves based on the location of the
seizure focus, and can have focal motor movements, sensory, autonomic,
or somatosensory symptoms. When
partial seizures are complex, they most often involve the temporal
lobe, and cause cognitive and affective abnormalities, and psychomotor
seizures. Other
generalized seizure types in children include neonatal seizures, benign
childhood epilepsy, infantile spasms, Lennox-Gastaut syndrome, atonic
seizures, and febrile seizures. These seizure types are more fully
addressed in the slide presentation. Status
epilepticus can be divided into convulsive, non-convulsive, and subtle
SE. Convulsive SE describes a generalized seizure that lasts greater
than 5-10 minutes. This
more aggressive SE definition shortens the seizure duration criteria
from 30 minutes, and is consistent with the treatment philosophy that
prompts paramedics, nurses and emergency physicians to treat seizures
early, regardless of duration.
Non-convulsive
SE includes a prolonged absence or complex partial seizure.
Complex partial SE may be present in a patient with waxing
and waning mental status and/or intermittent bizarre or unusual behavior.
Complex partial SE patients may also develop generalized seizures after
they present to the Emergency Department.
Subtle
status epilepticus, which is a late manifestation of prolonged SE
and is a sign of profound encephalopathy, may be the diagnosis in
frankly comatose patients who have only minimal focal motor activity.
In the past, a patient with subtle SE may have been considered less sick
than a patient with generalized convulsive SE (GCSE) because of the
absence of generalized seizure activity.
Up to 20% of comatose patients whose generalized seizures have
been terminated may continue to have ictal discharges on EEG.
The absence of clinical manifestations of SE leads to the designation
"subtle SE".
Patients who present
with or develop subtle SE are usually elderly patients with significant
co-morbidities and are more refractory to initial therapies, causing
a higher mortality rate, up to 50% at 30 days. Pre-hospital
Pediatric Seizure Therapy The
pre-hospital treatment of pediatric SE with diazepam has been shown
to reduce seizure duration by 47%, and to reduce the seizure recurrence
rate by 32%.
The Chicago EMS seizure SMOs allow for multiple 0.1 mg/kg doses
of diazepam in children prior to transport.
Rectal diazepam, dosed at 0.3-0.5 mg/kg, has been shown to
be safe and effective in seizing children when IV diazepam cannot
be given, and is often listed as a SMO alternative when IV access
is not available. Midazolam
is now being used more often in EMS SMOs, since it can be used effectively
via both the IV and IM routes, precluding the need for diazepam, which
requires rectal use when IV access is not possible.
EMS systems that utilize midazolam recommend multiple 0.1 mg/kg
doses in children.
Emergency
Department Evaluation A
complete laboratory evaluation may only be required in patients with
complicated or new-onset seizures, those in SE, or in patients with
significant co-morbidity and/or at the extremes of age.
One study of pediatric seizure patients established that the
need for routine chemistry testing was not justified, given the low
frequency of lab abnormalities.
The only significant lab abnormality that has been noted is
hypoglycemia, seen in up to 2% of seizing patients.
In
patients who seize for prolonged periods, up to 50% may present with
a temperature above 100.5, suggesting infection as the seizure etiology
and prompting a lumbar puncture (LP) to be considered. Fever, leukocytosis, and CSF pleocytosis may accompany SE even
in the absence of a CNS infection, complicating the ability to determine
the etiology of a prolonged seizure.
In
children, fevers commonly cause seizures and SE, despite the absence
of meningitis. With the
use of the HIB vaccine, the risk of meningitis is greatly reduced,
making meningitis as a possible cause of a prolonged febrile seizure
less likely. One study
demonstrated that a simple febrile seizure was never the sole finding
in a pediatric patient with meningitis.
The
published AAP guidelines that discuss the management of children with
febrile seizures, including the need for lumbar puncture, allow for
the Emergency Physician to defer most diagnostic tests except when
clinically indicated. This
is appropriate given the diminished possibility of CNS Haemophilus
influenzae b infection in children who have been HIB vaccinated, since
it had been the most common cause of meningitis in children in the
age group associated with febrile seizures.
The current ACEP guidelines also suggest that an LP is only
required in the presence of immunocompromise, meningeal signs, persistent
AMS, or a clinical history suggestive of a CNS infection. Neuroimaging
is indicated for seizures that are new-onset, complicated (including
SE), and in patients with co-morbid conditions that impart a greater
risk of complications. A
non-contrast head CT performed in the Emergency Department is a reasonable
first imaging study, since it may diagnose space occupying lesions,
mass effect, trauma, hemorrhage, and/or cerebrovascular infarcts.
Contrast-enhanced CT might only be necessary after the initial
non-contrast CT suggests a space occupying lesion that is better diagnosed
using contrast, such as a CNS tumor or an isodense subdural hematoma,
for example. One
study has demonstrated that children with complex febrile seizures,
a normal neurologic exam, and afebrile seizure patients without a
clear acute cause evident on history and physical rarely have a positive
CT, such that this test can be deferred if appropriate follow-up can
be arranged. The
use of electroencehalography (EEG) in the Emergency Department has
been limited, despite its ability to diagnose subtle SE in seizure
patients who remain comatose for prolonged periods after the termination
of a generalized seizure.
Only 12% of emergency
physicians report having access to EEG in the Emergency Department,
and only 15% have used it in the evaluation of suspected subtle SE.
An EEG should be considered whenever subtle SE or complex partial
SE is suspected, as well as in patients who require neuromuscular
paralysis, intubation, pentobarbital, and/or general anesthesia for
seizure control. For
example, if a child remains comatose for more than 30-40 minutes after
resolution of a prolonged seizure, an EEG might be useful in detecting
an ongoing seizure focus or SE.
The EEG could be performed upon arrival in the pediatric ICU
if this test is not routinely available in the ED.
Two
channel EEG monitors are available for use with Emergency Department
cardiac monitors that include changeable modular ports. This technology could allow the emergency physician to quickly
determine if persistent seizure activity is taking place, so that
additional therapy or consultation can take place prior to ICU disposition. Pediatric
Seizure and SE ED Therapy Recommendations
regarding the treatment of SE, published by the Working Group on Status
Epilepticus, provide the basis for optimal SE management in the Emergency
Department. Although
these guidelines are not specific for pediatric patients, they do
outline an initial diagnostic and treatment paradigm, including the
time course over which drug therapies should be provided.
Important aspects of this treatment guideline for emergency
physicians include the rapid implementation of an established treatment
protocol, adequate dosing on a mg/kg basis, so that refractory SE
can be treated as quickly as possible. There
are many standard and new therapies available to assist the emergency
physician in terminating seizures and SE.
Most uncomplicated seizure patients, including those who develop
SE, will respond to initial drug therapies in about 80% of cases.
More than the use of
a specific drug, the most important factors in seizure termination
are the rapid use of effective drugs in adequate doses, based on estimated
weights and mg/kg requirements.
Therapy can be optimized, therefore, by the development of
guidelines that include rational, sequential drug therapy that mandates
appropriate dosing prior to considering any individual AED to be ineffective.
Benzodiazepines,
which work through the GABA inhibition of repetitive firing, are easy
to use, rapid acting, with efficacy of at least 79% in the treatment
of SE. Alternate benzodiazepine
administration routes include intramuscular (IM), intranasal, and
buccal midazolam, as well as rectal emulsified diazepam.
When administered IM, midazolam only takes 116 seconds to terminate
seizures, as compared to 34 seconds when given by the intravenous
(IV) route. Intranasal
and buccal midazolam have also been shown to be as effective as diazepam
in randomized, controlled clinical trials.
The new form of rectal
diazepam, called Diastat, comes pre-packaged as an emulsion that can
be given rectally without the need to draw up the diazepam in a tuberculin
syringe or to tape or hold the buttocks together while the drug is
being absorbed. At a
minimum, these alternate benzodiazepine routes should make it unnecessary
to infuse AEDs via the interosseous route. Phenytoins
work though membrane Na+ and Ca+ channel stabilization,
reducing the likelihood of repetitive neuronal firing.
The standard phenytoin dose of 18-20 mg/kg is rarely exceeded
in the treatment of SE, even though high dose (30 mg/kg) phenytoin
therapy is recommended for SE refractory to standard phenytoin loading
doses. Fosphenytoin,
the water-soluble pro-drug of phenytoin, is dosed in phenytoin equivalents,
making dosing comparable to that of phenytoin.
It can be infused more rapidly than phenytoin with less pain,
fewer injection site reactions, and fewer adverse events. A loading dose of fosphenytoin can be given IM with therapeutic
phenytoin within 20-30 minutes.
Barbiturates
are an effective class of AEDs that work through the enhancement of
GABA inhibition of neuronal firing.
Although phenobarbital effectively treats seizures and SE,
its formulation, administration difficulties, and long half-life all
limit its usefulness in the Emergency Department.
Pentobarbital, when used as an anesthetic in the treatment
of refractory SE, requires airway management, extensive cardiovascular
and EEG monitoring, and neurologic consultation.
IV
valproate, called Depacon, is now available for use in Emergency Department
seizure patients who require rapid therapeutic drug level restoration.
This drug can be loaded in doses of 25-30 mg/kg at rates up
to 3-6 mg/kg/min (to a maximum rate of 300 mg/min) in children as
young as 2-3 months of age without significant complications.
Because many of the seizure etiologies in children warrant
long-term PO divalproex therapy, it is reasonable to load pediatric
patients who require protection from or therapy for SE with IV valproate.
There
have been case reports of the use of lidocaine in the treatment of
seizing patients refractory to conventional therapies.
Although this Na+ channel drug is not likely to
terminate most cases of SE, it can be used safely and should be considered
when the use of the initial therapies fail to terminate SE.
Refractory
SE, defined as SE non-responsive to initial therapy with benzodiazepines,
phenytoins, phenobarbital, and valproate, occurs in up to 22,000 patients
per year. In a case report
of an actively seizing pediatric patient, propofol was successfully
used to treat the refractory SE.
It is an anesthetic agent that may be used to treat SE because
it provides burst suppression through GABA inhibition.
Besides pentobarbital and propofol, midazolam can be given
as constant IV infusion for refractory SE, or inhalation anesthetics
can be used to achieve EEG burst-suppression.
Special
Considerations in Pediatric Seizures and SE In
pediatric head trauma patients, it has been shown that patients with
a GCS of 3-8 are at greatest risk for developing seizures.
Although long-term seizures are not prevented through the prophylactic
use of AEDs such as phenytoin or valproate in these patients, the
occurrence of early seizures (during the acute hospitalization) can
be prevented with seizure prophylaxis. As
was stated previously, many of the seizure etiologies that cause seizures
and SE in children and adolescents can be optimally treated long term
with PO divalproex. It
is reasonable, therefore, to consider IV valproate as one of the initial
therapies to be used when treating pediatric patients.
One specific seizure etiology that highlights this treatment
guideline is juvenile myoclonic epilepsy (JME).
College
students who are often sleep deprived and who have ingested alcohol,
may present with an early morning generalized seizure. These patients might have a history consistent with absence
seizures as a child, but no specific work-up or seizure therapy.
In these patients, valproate is the optimal drug to be used
if an ED load is required, since phenytoin can, in fact, worsen the
symptoms of JME when it is used long term.
Conclusions Pediatric
seizures and SE are neurologic emergencies that require prompt and
effective treatment by emergency care providers.
Outcome can be enhanced for all of these patients by providing
consistent care that follows a protocol, using effective drugs in
adequate doses. Future
research will continue to establish how pediatric patient outcome
can be improved through better use of current treatment modalities
and the development of new therapies that can be effectively used
in the emergency setting.
Emergency
Drugs: Pediatric Seizures
and Status Epilepticus (SE) Diazepam
IV
0.1-0.2 mg/kg per dose
10 kg = 1-2 mg
PR
0.5 mg/kg per dose 10
kg = 5 mg Diazepam
Rectal Gel
PR
0.5 mg/kg per dose 10
kg = 5 mg Lorazepam
IV
0.05-0.1 mg/kg per dose
10 kg = 0.5-1 mg Midazolam
IV
0.05-0.1 mg/kg per dose
10 kg = 0.5-1 mg
IM
0.08-0.2 mg/kg per dose
10 kg = 0.8-2 mg
Buccal 0.2
mg/kg per dose
10 kg = 2 mg Fosphenytoin
IV
20 mg PE/kg x 1.5 doses
10 kg = 200 mg
Rate up to 2 mg/kg/min
10 kg = 20 mg/min (10 min load)
For each 1 mg/kg given, level goes up 1 microgr/ml
Therapeutic level = 10-20 microgr/ml
IM
Same dose. May
be given in 1-4 IM injections. Valproate
IV
10-30 mg/kg
10 kg = 100-300 mg
Rate up to 3-6 mg/kg/min
10 kg = 30-60 mg/min (5-10 min)
Maximum infusion rate = 300 mg/min
For each 1 mg/kg given, level goes up 5 microgr/ml Therapeutic level = 50-150 microgr/ml Pediatric
Seizures and Status Epilepticus (SE):
|