1. No category

CLINICAL PRACTICE
Evaluation and Management of Status Epilepticus
in the Neurological Intensive Care Unit
Réza Behrouz, DO
Shirley Chen, DO
William O. Tatum, IV, DO
Status epilepticus (SE) is a common and potentially lifethreatening neurologic emergency characterized by prolonged seizures that are the result of primary neurologic
disease or secondary to critical illness and medical management. It is associated with high rates of morbidity and
mortality. Unfortunately, presentation is subclinical in many
cases and requires a high index of suspicion. The authors discuss diagnostic and management schemes for SE in the neurological intensive care unit, emphasizing the importance of
reducing the duration of SE through prompt recognition
and aggressive treatment protocols.
J Am Osteopath Assoc. 2009;109:237-245
S
tatus epilepticus (SE) is a common and potentially lifethreatening neurologic emergency characterized by prolonged seizures.1 The reported annual frequency of cases in
the United States has been between 102,000 and 152,000,
with roughly 55,000 of these incidents proving fatal.2 Because
estimates of mortality range from 17% to 23% and morbidity
from 10% to 23%, the impact of SE is dramatic.3
Traditionally, SE was defined as continuous seizure
activity lasting more than 30 minutes—or two or more sequential seizures without full neurologic recovery between episodes.
However, because of the high morbidity and mortality rates
associated with continuous seizures, the duration of seizure
activity defining SE has been reduced to 5 minutes.4
It is well known that the longer a seizure lasts, the likelihood that it will spontaneously cease diminishes.5 Therefore,
appropriate treatment for prolonged seizures should be initiated as early as possible.
Patients who are admitted to the neurological intensive
care unit (neuro-ICU) are more likely to have a primary brain
disorder than patients in other critical care settings. These
patients have symptomatic causes for SE and are more apt to
progress to this condition.
Many hospitals worldwide now have dedicated neuroICUs for patients with diseases that affect the central nervous
system (CNS). Specialized neurocritical care teams have been
shown to improve patient outcomes, maximizing resource
utilization and reducing hospital mortality.6 The current article
specifically addresses clinical management of SE in the neuroICU setting.
Status epilepticus and seizures in the neuro-ICU are often
the result of a primary disease of the brain. Patients who are
admitted to the neuro-ICU suffer from a variety of traumatic
and nontraumatic cerebral disorders that can predispose them
to SE. These conditions, among others, include cerebral venous
thrombosis, intracranial hemorrhage, large cerebral infarction
or intracranial neoplasm, meningitis or encephalitis, postcraniotomy, and traumatic brain injury.
Both generalized convulsive (GCSE) and nonconvulsive
(NCSE) forms of SE can occur in neuro-ICU patients. As the
name implies, GCSE is a condition where seizures are clinically
manifested as generalized tonic-clonic movements or “convulsions.” Alternatively, NCSE is generally subclinical or associated with subtle clinical findings.7
Continuous electroencephalographic (EEG) monitoring is
essential for the detection of seizures with subtle or no clinical
manifestations. Such cases were previously described as “clinically unrecognized seizures.”8 These seizures are often discovered only with the assistance of EEG recording. By way of
example, the incidence of seizures for patients with intracerebral hemorrhage reaches 1 in 3 cases—yet only half of these
occurrences are clinically observable on bedside examination,
the rest being purely electrographic.8
Pathophysiology
From the Department of Neurology at the University of South Florida College
of Medicine in Tampa. Dr Tatum is currently at Mayo Clinic in Jacksonville, Fla.
Address correspondence to Réza Behrouz, DO, Tampa General Hospital,
2A Columbia Dr, Fl 7, Tampa, FL 33606-3508.
E-mail: rbehrouz @health.usf.edu
Submitted March 25, 2008; revision received September 4, 2008; accepted
September 5, 2008.
Behrouz et al • Clinical Practice
Downloaded From: http://jaoa.org/ on 04/15/2015
Status epilepticus results from a combination of persistent cellular excitation and a failure of centrally mediated mechanisms to suppress sustained seizure activity.9
There is evidence to suggest that in early SE, the predominant mechanism responsible is failure of ␥-aminobutyric
acid, or GABA, the primary inhibitory neurotransmitter of
the CNS, to suppress the activated seizure focus. In later stages,
the amino acid derivative N-methyl-D-aspartate, which causes
JAOA • Vol 109 • No 4 • April 2009 • 237
CLINICAL PRACTICE
neuronal excitation, becomes more important in sustaining
seizure activity.10
Postmortem studies indicate that the key anatomic structures involved in the pathogenesis of SE are the hippocampus
and associated limbic system.11 These findings were present
even for patients who did not have a preexisting diagnosis of
epilepsy.
Generalized SE is also associated with several systemic
physiologic changes, all of which occur as a result of a massive
release of catecholamines. Early manifestations (ie, during the
first 30 minutes of SE) include cardiac arrhythmia, hyperglycemia, hypertension, lactic acidosis, and tachycardia. Just
beyond 30 minutes, blood pressure and glucose concentration may begin to normalize, or even reverse in abnormality.
Prolonged SE (ie, beyond 60 minutes) may be associated
with hyperthermia, hypoglycemia, hypotension, pulmonary
edema, renal failure, and rhabdomyolysis.12 Cerebral ischemia
from hypoperfusion may even occur, the areas most susceptible being the limbic and cortical structures.13
Alcohol withdrawal
Anoxia
Antiepileptic drug withdrawal
Central nervous system infection
Cerebral infarction
Congenital brain injury
Cranial neoplasm
Illicit drug overdose
Intracranial hemorrhage
Metabolic derangement
Status epilepticus of idiopathic origin
Systemic infection or sepsis
Traumatic brain injury
Figure 1. Leading causes of status epilepticus.19
Frequency and Causes
To our knowledge, a systematic analysis of SE frequency in the
neuro-ICU based on etiology has not yet been performed.
Although SE prevalence in common disorders warranting
admission to the neuro-ICU can be delineated, the causes are
legion. A cohort study involving more than 800,000 patients
reported 0.2% and 0.3% prevalence of SE in acute ischemic
stroke and intracerebral hemorrhage, respectively.14
Continuous EEG monitoring has helped to elucidate cases
defined with clinical and subclinical NCSE. Studies of patients
with subarachnoid hemorrhage have revealed an SE rate of 8%,
while a nationwide survey of patients with nontraumatic subarachnoid hemorrhage reported a rate of 0.2% for GCSE.15,16
For patients with traumatic brain injury, this rate is anywhere
from 1.9% to 8%.17 In children especially, acute bacterial meningitis can cause rates of SE as high as 12%.18 The frequency of
SE for other conditions that are generally managed in the
neuro-ICU is unknown.
Aside from primary neurologic disease, toxic and
metabolic factors may also play a role in causing seizures that
progress to SE. Such factors can be the initiating cause of
seizures, aggravate an underlying epileptogenic focus in the
brain, or prolong a preexisting seizure (Figure 1).19
Several medications used in the neuro-ICU may lower
seizure threshold, including various antibiotics that are used
for managing CNS infections. Patients with impaired renal
function receiving cephalosporins or ␤-lactam antibiotics are
especially at risk.20,21
In addition, electrolyte imbalances may result directly
from brain injury or treatment thereof. Examples are hyponatremia due to cerebral salt-wasting and hypernatremia resulting
from central diabetes insipidus or aggressive, unmonitored
hypertonic saline therapy for cerebral edema. Acid-base dis238 • JAOA • Vol 109 • No 4 • April 2009
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turbances—particularly severe alkalosis caused either by
aggressive alkaline therapy or inappropriate ventilator management—are also precipitating factors.
Many patients admitted to the neuro-ICU may have a
preexisting history of epilepsy (due to various cerebral lesions)
and may already be on an antiepileptic drug (AED). Discontinuation of these medications may lead to withdrawal and subsequently to SE.
Likewise, voluntary withdrawal from alcohol, barbiturates, or benzodiazepines is often overlooked as a cause of SE
among critically ill patients.
Finally, encephalopathy from sepsis or either hepatic or
renal failure can potentially lead to SE.
Morbidity and Mortality
The most common short-term sequelae related to SE include
infection, respiratory complications, and impairment of mental
status.22 Potential long-term morbidity consists of focal neurologic deficits, cognitive impairment, subsequent development of epilepsy—and recurrent SE, which has been reported
at rates of 3% to 13%.23 Although the exact risk of developing
these sequelae is unclear, they appear to depend largely on the
underlying etiologic process.22
Several factors can have a substantial impact on 30-day
mortality, namely patient age and the etiology and duration of
SE. With respect to age, there is a bimodal distribution for
high mortality rates, with peak rates in neonates and elderly
patients.24 Significantly increased mortality is also associated
with SE duration of more than 30 minutes, which has been
reported at 19% to 32%, compared to shorter duration SE
being less than 3%.19,25
Behrouz et al • Clinical Practice
CLINICAL PRACTICE
Figure 2. Continuous electroencephalographic (EEG) monitoring is an effective method for detecting nonconvulsive status epilepticus. Confused, stuporous, or comatose patients may demonstrate rapid, rhythmic epileptiform discharge on the EEG, as shown here. The diagnosis of
nonconvulsive status epilepticus therefore involves a combination of abnormal mental status with diminished responsiveness, supportive EEG
results, and a response to anticonvulsants.33
Etiology may also be a determinant in mortality for SE.
Although anoxia with SE carries the highest risk of mortality,
a synergistic effect is not apparent; mortality for anoxia alone
is just as high in the absence of SE.26 However, there is evidence
to support a synergistic effect on mortality from SE in association with acute symptomatic etiologies, especially acute
ischemic stroke.27
In addition, multiple medical comorbidities may also contribute to increased mortality rates.28 Etiologies associated
with low mortality rates were alcohol withdrawal and subtherapeutic levels of AEDs.19
Of all three factors noted above to have a substantial
impact on 30-day mortality rates, the only potentially modifiable determinant is duration.24 It is for this reason that the
most important focus point for clinicians involved in the care
of patients with SE is prompt recognition and immediate initiation of treatment.
Behrouz et al • Clinical Practice
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Diagnosis
As noted, prompt diagnosis of SE substantially impacts patient
health, transforming a life-threatening process into a treatable
and completely reversible clinical entity. Generalized convulsive SE is primarily diagnosed by its clinically recognizable presentation: consciousness is invariably impaired. An EEG is
used to confirm diagnosis.
In the presence of clinical symptoms or high index of suspicion for an ongoing seizure, treatment should not be delayed
to obtain EEG confirmation. Typical clinical presentations of
GCSE are tonic-clonic, though this condition may also present as myoclonic or—less frequently—tonic, clonic, or mixed
seizure types.
At least one-third of all cases of SE are nonconvulsive.29
This condition occurs in approximately 8% of comatose
patients,30 22% of patients with severe head injury,31 and as
many as 34% of patients admitted to the neuro-ICU.32
JAOA • Vol 109 • No 4 • April 2009 • 239
CLINICAL PRACTICE
Prolonged coma should always raise the index of suspicion for NCSE. Continuous EEG monitoring is an effective
method of detection. Confused, stuporous, or comatose patients
may demonstrate a rapid, rhythmic epileptiform discharge
on EEG (Figure 2). The diagnosis of NCSE therefore involves
a combination of abnormal mental status with diminished
responsiveness, supportive EEG results—and, often, a response
to anticonvulsants.33
Laboratory studies on initial diagnosis of SE include rapid
evaluation of blood glucose and electrolyte panel (eg, serum
magnesium and sodium), screening for drugs of abuse as well
as AED levels if medical history includes epilepsy.
Management
Because SE is a life-threatening process, patients who receive
this diagnosis should also receive prompt direction to treatment. The goal of therapy is rapid termination of clinical and
electrical seizure activity.
Once a diagnosis has been established, treatment should
follow (Figure 3):
1. Assess airway, breathing, and circulation.
2. Stop the seizure.
3. Find the underlying cause.
4. Correct it.
To minimize neural damage, resuscitation, correction of
metabolic defects, and seizure termination should be achieved
rapidly. Treatment should be aggressive with intravenous
(IV) therapy used when possible.
The first step in management of GCSE is ensuring a secure
airway. If required, endotracheal intubation of the patient
should be undertaken promptly, especially when there is loss
of pharyngeal tone due to prolonged seizures. In difficult situations, as for patients with GCSE, short-acting paralytics
(succinylcholine chloride) and hypnotics (etomidate) may be
used to facilitate intubation (ie, rapid sequence protocol). Once
a patient is paralyzed, it is essential to provide continuous
EEG monitoring because brain seizures may continue despite
the absence of physical manifestations.
Once the airway is secure, the next step is to break the
seizure by IV administration of benzodiazepines, such as
lorazepam, 4 mg, or diazepam, 10 mg, for adults (Figure 4). The
preferred route of administration is IV, and access should be
obtained as soon as possible. Should IV access be unavailable,
however, these benzodiazepines can be administered intramuscularly. Diazepam also comes in a rectal formulation.
Intravenous lorazepam is the most widely used benzodiazepine in the initial treatment of SE. Furthermore, it is the
medication of choice because it is associated with a longer
effective CNS half-life than diazepam with a lower risk of
early relapse.34,35 The Veterans Affairs Status Epilepticus Cooperative Study Group36 compared IV lorazepam to diazepam
240 • JAOA • Vol 109 • No 4 • April 2009
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(plus phenytoin sodium), phenobarbital, and phenytoin with
a success rate of 64.9%.
Benzodiazepine therapy is followed by IV administration
of a prodrug or anticonvulsant, respectively: fosphenytoin
sodium, 10 mg PE/kg, or phenytoin, 10 mg/kg. Use of fosphenytoin has several advantages, namely more convenient
and rapid IV administration (ie, 150 mg/min vs phenytoin’s
50 mg/min), intramuscular administration when necessary,
and low incidence of adverse reaction at the site of injection.37
Also, the hemodynamic instability generally associated with
phenytoin is rarely a problem with fosphenytoin.38
For patients with benzodiazepine refractory SE, IV valproic
acid may be as effective as—and better tolerated than—phenytoin.39 Valproic acid can be used as an alternative to phenytoin,
especially in cases where comorbid cardiac disease or severe
hemodynamic instability are present.39-41
If seizures continue for more than 10 minutes after the first
injection of an IV benzodiazepine, a second dose is recommended.42 After initial administration of lorazepam, response
to treatment undergoes rapid decline. The Veterans Affairs
cooperative study36 demonstrated that the aggregate response
to a repeat dose of AEDs was 7.0%; to the third, 2.3%.
After the initial dose of fosphenytoin, additional anticonvulsants may be used intravenously: phenobarbital, 1020 mg/kg (25-50 mg/min); valproic acid, 20 mg/kg; or levetiracetam, 20 mg/kg. Specific conditions may prove more
responsive to one or the other AED, however. For example, in
status myoclonus associated with hypoxia, both valproic acid
and levetiracetam43 have been used successfully, and a
response to propofol has also been shown.44 In a patient with
a history of idiopathic generalized epilepsy who is in SE, the
use of phenytoin or fosphenytoin may exacerbate GCSE.45
Early institution of valproic acid in such cases has been a successful alternative.45
Treatment with IV lorazepam or with diazepam and
phenytoin will control seizures in as many as 70% of patients.46
Refractory SE occurs when seizures become resistant to the initial therapeutic dose of benzodiazepine. Continuous IV infusion
with midazolam, propofol, or pentobarbital sodium has been
used for patients with refractory SE.47
To prevent the occurrence of propofol-infusion syndrome,
prolonged (⬎48 hours) and high (⬎5 mg/kg/hr) doses of
propofol should be avoided. Propofol-infusion syndrome is a
rare but potentially fatal disorder characterized by refractory
cardiac arrhythmia and at least one of the following conditions:
hepatomegaly, hyperlipidemia, metabolic acidosis, or rhabdomyolysis.48 This syndrome is most likely to occur in children,
patients with severe brain or lung injury, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake, or subclinical mitochondrial disease.49
Continuous EEG monitoring is necessary during clinical
management of refractory SE to ensure treatment success by
demonstrating the absence of ongoing electrographic seizures.
Behrouz et al • Clinical Practice
CLINICAL PRACTICE
Evaluation and Management of Status Epilepticus
in the Neurological Intensive Care Unit
Réza Behrouz, DO
Shirley Chen, DO
William O. Tatum, IV, DO
Status epilepticus (SE) is a common and potentially lifethreatening neurologic emergency characterized by prolonged seizures that are the result of primary neurologic
disease or secondary to critical illness and medical management. It is associated with high rates of morbidity and
mortality. Unfortunately, presentation is subclinical in many
cases and requires a high index of suspicion. The authors discuss diagnostic and management schemes for SE in the neurological intensive care unit, emphasizing the importance of
reducing the duration of SE through prompt recognition
and aggressive treatment protocols.
J Am Osteopath Assoc. 2009;109:237-245
S
tatus epilepticus (SE) is a common and potentially lifethreatening neurologic emergency characterized by prolonged seizures.1 The reported annual frequency of cases in
the United States has been between 102,000 and 152,000,
with roughly 55,000 of these incidents proving fatal.2 Because
estimates of mortality range from 17% to 23% and morbidity
from 10% to 23%, the impact of SE is dramatic.3
Traditionally, SE was defined as continuous seizure
activity lasting more than 30 minutes—or two or more sequential seizures without full neurologic recovery between episodes.
However, because of the high morbidity and mortality rates
associated with continuous seizures, the duration of seizure
activity defining SE has been reduced to 5 minutes.4
It is well known that the longer a seizure lasts, the likelihood that it will spontaneously cease diminishes.5 Therefore,
appropriate treatment for prolonged seizures should be initiated as early as possible.
Patients who are admitted to the neurological intensive
care unit (neuro-ICU) are more likely to have a primary brain
disorder than patients in other critical care settings. These
patients have symptomatic causes for SE and are more apt to
progress to this condition.
Many hospitals worldwide now have dedicated neuroICUs for patients with diseases that affect the central nervous
system (CNS). Specialized neurocritical care teams have been
shown to improve patient outcomes, maximizing resource
utilization and reducing hospital mortality.6 The current article
specifically addresses clinical management of SE in the neuroICU setting.
Status epilepticus and seizures in the neuro-ICU are often
the result of a primary disease of the brain. Patients who are
admitted to the neuro-ICU suffer from a variety of traumatic
and nontraumatic cerebral disorders that can predispose them
to SE. These conditions, among others, include cerebral venous
thrombosis, intracranial hemorrhage, large cerebral infarction
or intracranial neoplasm, meningitis or encephalitis, postcraniotomy, and traumatic brain injury.
Both generalized convulsive (GCSE) and nonconvulsive
(NCSE) forms of SE can occur in neuro-ICU patients. As the
name implies, GCSE is a condition where seizures are clinically
manifested as generalized tonic-clonic movements or “convulsions.” Alternatively, NCSE is generally subclinical or associated with subtle clinical findings.7
Continuous electroencephalographic (EEG) monitoring is
essential for the detection of seizures with subtle or no clinical
manifestations. Such cases were previously described as “clinically unrecognized seizures.”8 These seizures are often discovered only with the assistance of EEG recording. By way of
example, the incidence of seizures for patients with intracerebral hemorrhage reaches 1 in 3 cases—yet only half of these
occurrences are clinically observable on bedside examination,
the rest being purely electrographic.8
Pathophysiology
From the Department of Neurology at the University of South Florida College
of Medicine in Tampa. Dr Tatum is currently at Mayo Clinic in Jacksonville, Fla.
Address correspondence to Réza Behrouz, DO, Tampa General Hospital,
2A Columbia Dr, Fl 7, Tampa, FL 33606-3508.
E-mail: rbehrouz @health.usf.edu
Submitted March 25, 2008; revision received September 4, 2008; accepted
September 5, 2008.
Behrouz et al • Clinical Practice
Downloaded From: http://jaoa.org/ on 04/15/2015
Status epilepticus results from a combination of persistent cellular excitation and a failure of centrally mediated mechanisms to suppress sustained seizure activity.9
There is evidence to suggest that in early SE, the predominant mechanism responsible is failure of ␥-aminobutyric
acid, or GABA, the primary inhibitory neurotransmitter of
the CNS, to suppress the activated seizure focus. In later stages,
the amino acid derivative N-methyl-D-aspartate, which causes
JAOA • Vol 109 • No 4 • April 2009 • 237
CLINICAL PRACTICE
Pharmacologic Management of Status Epilepticus
Medication
Intravenous Dosing
(Maximum Dose)
Maximum Rate
of Administration
Potential
Adverse Effects
Advantage(s)
of Treatment Modality
Lorazepam
Adult: 4 mg (Max, 8 mg/12 h)
Pediatric: 0.1 mg/kg (Max, 4 mg)
2 mg/min
Bolus, 2-5 min
▫ Respiratory depression
▫ Sedation
▫ Rapid onset of action
▫ Longer duration
of action than diazepam
▫ Can also administer
intramuscularly
Diazepam
Adult: 10 mg every 10-20 min
(Max, 30 mg/8 h)
Pediatric: 0.05-0.3 mg/kg
every 15-30 min (Max, 10 mg)
Bolus
▫ Respiratory depression
▫ Sedation
▫ Rapid onset of action
▫ Can also administer
intramuscularly or
rectally
Adult: Load 20 mg PE/kg
(Max, 30 mg PE/kg)
Pediatric: same
150 mg PE/min
▫ Arrhythmia
▫ Hypotension
▫ Pruritis
▫ Adverse effects rare
▫ Rapid rate
of administration
Phenytoin sodium Adult: Load 20 mg/kg
(Max, 30 mg/kg)
Pediatric: same
50 mg/min
▫ Arrhythmia
▫ Hypotension
▫ Prolonged QT interval
▫ Purple glove syndrome
Relatively inexpensive
Phenobarbital
Adult: Load 20 mg/kg
(Max, 40 mg/kg)
Pediatric: same
100 mg/min
▫ Hypotension
▫ Respiratory depression
▫ Sedation
Long half-life
Valproic acid
Adult: Load 20 mg/kg
(Max, 60 mg/kg/d)
Pediatric: same
20 mg/min
▫ Hepatic failure
▫ Pancreatitis
▫ Adverse effects rare
▫ Effective for
myoclonic seizures
Levetiracetam
Adult: Load 20 mg/kg
(Max, 3000 mg/d)
Pediatric (age ⭓16 y): same
15-min infusion
Sedation
▫ Well tolerated
▫ Effective for
myoclonic seizures
Midazolam
Adult: Load 0.2 mg/kg,
then 0.75 ␮g/kg/min
Pediatric: Load 0.15 mg/kg,
then 1 ␮g/kg/min
10 ␮g/kg/min
▫ Respiratory depression
▫ Sedation
Rapid onset of action
Propofol
Adult: Load 2 mg/kg,
then 100 ␮g/kg/min
Pediatric (age ⭓ 3 y):
Load 2.5-3.5 mg/kg,
then 125 ␮g/kg/min
200 ␮g/kg/min
▫ Hypotension
▫ Lipidemia
▫ Metabolic acidosis
▫ Propofol-infusion
syndrome
▫ Sedation
▫ Rapid onset of action
▫ Rapid elimination
Adult: Load 5-15 mg/kg,
then 5 mg/kg/h
Pediatric: same
50 mg/min
▫ Bradycardia
▫ Hypotension
▫ Respiratory depression
▫ Sedation
Rapid onset of action
Fosphenytoin
sodium
Pentobarbital
sodium
Bolus, 2-3 min
300 ␮g/kg/min
Figure 4. Intravenous therapy should be used when possible in the aggressive clinical management of status epilepticus. Abbreviation: PE, administered and dispensed in phenytoin sodium equivalent units.
A “burst-suppression” pattern on the EEG (Figure 5) is the
goal of pharmacologic treatment, though the precise clinical
necessity and parameters currently remain unvalidated in the
medical literature.50
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During the next 24 to 48 hours, patients diagnosed with
SE are slowly weaned from IV infusion if EEG results indicate
resolution of electrographic seizure.
There is no consensus as to the length of time patients
Behrouz et al • Clinical Practice
CLINICAL PRACTICE
Figure 5. Continuous electroencephalographic monitoring is necessary during treatment of refractory status epilepticus to ensure treatment
success by demonstrating absence of ongoing electrographic seizures. A “burst-suppression” pattern on an electroencephalograph, as shown
here, is the goal of pharmacologic treatment though the precise clinical necessity and parameters remain unvalidated in the medical literature.50
should be kept in a “therapeutic coma.” Unfortunately, there
are scenarios where cessation of SE becomes an impossible
task in spite of aggressive therapy.
It is important to note that, despite termination of clinically
obvious seizure activity, some patients may continue to have
subclinical seizures that are detectable electrographically by
EEG. In more than 14% of cases where patients are successfully
treated for convulsive SE, they may continue to have NCSE.51
It is therefore imperative to obtain EEG monitoring if a patient
remains with altered sensorium after successful treatment of
convulsive SE, especially if no other reasonable explanation for
the condition exists.
Conclusion
Status epilepticus is a common and serious condition encountered in the neuro-ICU. It is associated with an estimated morBehrouz et al • Clinical Practice
Downloaded From: http://jaoa.org/ on 04/15/2015
tality rate of 20%.2,52 Although clinical studies show little evidence to document the effects of permanent neurologic injury
in NCSE, prolonged memory dysfunction and the similarities to convulsive status suggest that this condition should be
managed expeditiously.33
Rapid treatment requires prompt recognition of SE’s signs
and symptoms and a high index of suspicion for this condition.
Ideally, medical care should be guided closely by a neurologic specialist in the ICU. No matter what medications are
selected, a goal-directed protocol is essential in facilitating
delivery of appropriate treatment as efficiently as possible.
As more treatment modalities become available, a focus
of newer therapies will be on minimizing the consequences of
electrophysiologic insults—in addition to seizure suppression. Neuroprotective agents may become useful to prevent the
cascade of delayed neuronal injury.
(continued)
JAOA • Vol 109 • No 4 • April 2009 • 243
CLINICAL PRACTICE
In the future, a combination of treatments including
seizure suppressants that are capable of becoming maintenance AEDs, neuroprotectants such as N-methyl-D-aspartate
antagonists, free radical scavengers, second messenger modulators (ie, nitric oxide or adenosine), and earlier therapies
may become available for the many as yet unrecognized incidents of SE in the neuro-ICU.
References
1. Tatum IV WO [sic], French JA, Benbadis SR, Kaplan PW. The etiology and
diagnosis of status epilepticus. Epilepsy Behav. 2001;2:311-317.
2. Lowenstein DH, Alldredge BK. Status epilepticus [review]. N Engl J Med.
1998;338:970-976.
3. Pang T, Hirsch LJ. Treatment of convulsive and nonconvulsive status epilepticus. Curr Treat Options Neurol. 2005;7:247-259.
4. Lowenstein DH. Status epilepticus: an overview of the clinical problem
[review]. Epilepsia. 1999;40(suppl 1):S3-S8.
5. García Peñas JJ, Molins A, Salas Puig J. Status epilepticus: evidence and
controversy [review]. Neurologist. 2007;13(6 suppl 1):S62-S73.
6. Suarez JI. Outcome in neurocritical care: advances in monitoring and treatment and effect of a specialized neurocritical care team [review]. Crit Care Med.
2006;34(9 suppl):S232-S238.
19. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in
status epilepticus. Epilepsia. 1994;35:27-34.
20. Chetaille E, Hary L, de Cagny B, Gras-Champel V, Decocq G, Andréjak M.
Convulsive crisis associated with an overdose of cefepime [in French]. Therapie. 1998;53:167-168.
21. Ferrara N, Abete P, Giordano M, Ferrara P, Carnovale V, Leosco D, et al.
Neurotoxicity induced by cefepime in a very old hemodialysis patient. Clin
Nephrol. 2003;59:388-390.
22. Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in
nonconvulsive status epilepticus. Neurology. 2003;61:1066-1073.
23. Holtkamp M, Othman J, Buchheim K, Meierkord H. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care
unit. J Neurol Neurosurg Psychiatry. 2005;76:534-539. Available at:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedi
d=15774441. Accessed March 23, 2009.
24. Boggs JG. Mortality associated with status epilepticus. Epilepsy Curr.
2004;4:25-27. Available at: http://www.pubmedcentral.nih.gov/articlerender
.fcgi?tool=pubmed&pubmedid=15346141. Accessed March 23, 2009.
25. DeLorenzo RJ, Garnett LK, Towne AR, Waterhouse EJ, Boggs JG, Morton
L, et al. Comparison of status epilepticus with prolonged seizure episodes
lasting from 10 to 29 minutes. Epilepsia. 1999;40:164-169.
7. Treiman DM. Electroclinical features of status epilepticus [review]. J Clin Neurophysiol. 1995;12:343-362.
26. Dumot JA, Burval DJ, Sprung J, Waters JH, Mraovic B, Karafa MT, et al. Outcome of adult cardiopulmonary resuscitations at a tertiary referral center
including results of “limited” resuscitations. Arch Intern Med. 2001;161:17511758. Available at: http://archinte.ama-assn.org/cgi/content/full/161/14/1751.
Accessed March 23, 2009.
8. Claassen J, Jetté N, Chum F, Green R, Schmidt M, Choi H, et al. Electrographic
seizures and periodic discharges after intracerebral hemorrhage. Neurology.
2007;69:1356-1365.
27. Waterhouse EJ, Vaughan JK, Barnes TY, Boggs JG, Towne AR, KopecGarnett L, et al. Synergistic effect of status epilepticus and ischemic brain
injury on mortality. Epilepsy Res. 1998;29:175-183.
9. Manno EM. New management strategies in the treatment of status epilepticus [review]. Mayo Clin Proc. 2003;78:508-518.
28. Delanty N, French JA, Labar DR, Pedley TA, Rowan AJ. Status epilepticus
arising de novo in hospitalized patients: an analysis of 41 patients. Seizure.
2001;10:116-119.
10. Borris DJ, Bertram EH, Kapur J. Ketamine controls prolonged status epilepticus. Epilepsy Res. 2000;42:117-122.
11. Wasterlain CG, Fujikawa DG, Penix L, Sankar R. Pathophysiological mechanisms of brain damage from status epilepticus [review]. Epilepsia.
1993;34(suppl 1):S37-S53.
12. Lothman E. The biochemical basis and pathophysiology of status epilepticus [review]. Neurology. 1990;40(5 suppl 2):13-23.
13. Walton NY. Systemic effects of generalized convulsive status epilepticus
[review]. Epilepsia. 1993;34(suppl 1):S54-S58.
14. Bateman BT, Claassen J, Willey JZ, Hirsch LJ, Mayer SA, Sacco RL, et al. Convulsive status epilepticus after ischemic stroke and intracerebral hemorrhage:
frequency, predictors, and impact on outcome in a large administrative
dataset. Neurocrit Care. 2007;7:187-193.
15. Dennis LJ, Claassen J, Hirsch LJ, Emerson RG, Connolly ES, Mayer SA.
Nonconvulsive status epilepticus after subarachnoid hemorrhage. Neurosurgery. 2002;51:1136-1143.
16. Claassen J, Bateman BT, Willey JZ, Inati S, Hirsch LJ, Mayer SA, et al. Generalized convulsive status epilepticus after nontraumatic subarachnoid hemorrhage: the nationwide inpatient sample. Neurosurgery. 2007;61:60-64.
17. Peets AD, Berthiaume LR, Bagshaw SM, Federico P, Doig CJ, Zygun DA. Prolonged refractory status epilepticus following acute traumatic brain injury: a
case report of excellent neurological recovery [published online ahead of
print October 27, 2005]. Crit Care. 2005;9:R725-R728. Available at:
http://ccforum.com/content/9/6/R725. Accessed March 23, 2009.
18. Chin RF, Neville BG, Peckham C, Bedford H, Wade A, Scott RC; NLSTEPSS
Collaborative Group. Incidence, cause, and short-term outcome of convulsive
status epilepticus in childhood: prospective population-based study. Lancet.
2006;368:222-229.
244 • JAOA • Vol 109 • No 4 • April 2009
Downloaded From: http://jaoa.org/ on 04/15/2015
29. Walker MC. Diagnosis and treatment of nonconvulsive status epilepticus
[review]. CNS Drugs. 2001;15:931-939.
30. Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR Jr,
et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54:340-345.
31. Vespa PM, Nuwer MR, Nenov V, Ronne-Engstrom E, Hovda DA, Bergsneider
M, et al. Increased incidence and impact of nonconvulsive and convulsive
seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg. 1999;91:750-760.
32. Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures
in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology. 1996;47:83-89.
33. Drislane FW. Presentation, evaluation, and treatment of nonconvulsive
status epilepticus. Epilepsy Behav. 2000;1:301-314.
34. Henry JC, Holloway R. Review: lorazepam provides the best control for
status epilepticus. Evid Based Med. 2006;11:54.
35. Minicucci F, Muscas G, Perucca E, Capovilla G, Vigevano F, Tinuper P.
Treatment of status epilepticus in adults: guidelines of the Italian League
Against Epilepsy. Epilepsia. 2006;47(suppl):9-15.
36. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et
al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl
J Med. 1998;339:792-798. Available at: http://content.nejm.org/cgi
/content/full/339/12/792 . Accessed March 23, 2009.
37. Fischer JH, Patel TV, Fischer PA. Fosphenytoin: clinical pharmacokinetics and
comparative advantages in the acute treatment of seizures [review]. Clin
Pharmacokinet. 2003;42:33-58.
Behrouz et al • Clinical Practice
CLINICAL PRACTICE
38. Browne TR. Fosphenytoin (Cerebyx) [review]. Clin Neuropharmacol.
1997;20:1-12.
46. Durham D. Management of status epilepticus. Crit Care Resusc. 1999;1:344353.
39. Agarwal P, Kumar N, Chandra R, Gupta G, Antony AR, Garg N. Randomized study of intravenous valproate and phenytoin in status epilepticus [published online ahead of print July 9, 2007]. Seizure. 2007;16:527-532.
47. Holmes GL, Riviello JJ Jr. Midazolam and pentobarbital for refractory
status epilepticus [published correction appears in Pediatr Neurol. 1999;21:511].
Pediatr Neurol. 1999;20:259-264.
40. Peters CN, Pohlmann-Eden B. Intravenous valproate as an innovative
therapy in seizure emergency situations including status epilepticus—experience in 102 adult patients. Seizure. 2005;14:164-169.
48. Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of
propofol infusion syndrome: a simple name for a complex syndrome [review]
[published online ahead of print August 6, 2003]. Intensive Care Med.
2003;29:1417-1425.
41. Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid
IV administration of valproic acid for status epilepticus [review]. Neurology.
2005;64(2):353-355.
42. Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, et al. EFNS
guideline on the management of status epilepticus. Eur J Neurol. 2006;13:445450.
43. Krauss GL, Bergin A, Kramer RE, Cho YW, Reich SG. Suppression of posthypoxic and post-encephalitic myoclonus with levetiracetam. Neurology.
2001;56:411-412.
44. Stecker MM, Kramer TH, Raps EC, O’Meeghan R, Dulaney E, Skaar DJ. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia. 1998;39:18-26.
49. Kam PC, Cardone D. Propofol infusion syndrome [review]. Anaesthesia.
2007;62:690-701.
50. Bleck TP. Management approaches to prolonged seizures and status
epilepticus [review]. Epilepsia. 1999;40(suppl 1):S59-S63.
51. DeLorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA,
et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia. 1998;39:833-840.
52. DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy
L, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46:1029-1035.
45. Uberall MA, Trollmann R, Wunsiedler U, Wenzel D. Intravenous valproate
in pediatric epilepsy patients with refractory status epilepticus. Neurology.
2000;54:2188-2189.
JAOA call for case reports
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Osteopathic Association invites osteopathic physicians, researchers, and others in the healthcare
professions to submit case reports relevant to osteopathic medicine.
In preparing submissions, authors should adhere to the JAOA‘s “Information for Contributors,”
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