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Refractory Status Epilepticus
Frequency, Risk Factors, and Impact on Outcome
Stephan A. Mayer, MD;
Jan Claassen, MD;
Johnny Lokin, MD;
Felicia Mendelsohn, BA;
Lyle J. Dennis, MD;
Brian-Fred Fitzsimmons, MD
Arch Neurol. 2002;59:205-210.
ABSTRACT
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Background Refractory status epilepticus (RSE) is a life-threatening condition
in which seizures do not respond to first- and second-line anticonvulsant
drug therapy. How often RSE occurs, risk factors that predispose to this condition,
and the effect of failure to control seizures on clinical outcome are poorly
defined.
Objective To determine the frequency, risk factors, and impact on outcome of RSE.
Design Retrospective cohort study.
Setting Large academic teaching hospital.
Patients Consecutive sample of 83 episodes of status epilepticus in 74 patients
(mean age, 63 years).
Main Outcome Measures Refractory status epilepticus was defined as seizures lasting longer
than 60 minutes despite treatment with a benzodiazepine and an adequate loading
dose of a standard intravenous anticonvulsant drug. Factors associated with
RSE were identified using univariate and backward stepwiselogistic regression
analyses.
Results In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine,
and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant
drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE
(P= .03) and focal motor seizures at onset (P= .04) were identified as independent risk factors for
RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line
agent (usually phenobarbital). Although mortality was not increased (17% overall),
RSE was associated with prolonged hospital length of stay (P<.001) and more frequent functional deterioration at discharge
(P= .02).
Conclusions Refractory status epilepticus occurs in approximately 30% of patients
with SE and is associated with increased hospital length of stay and functional
disability. Nonconvulsive SE and focal motor seizures at onset are risk factors
for RSE. Randomized controlled trials are needed to define the optimal treatment
of RSE.
INTRODUCTION
STATUS EPILEPTICUS (SE) is a life-threatening condition that affects
120 000 to 200 000 people annually in the United States.1 In its most severe form, refractory SE (RSE), continuous
or repetitive seizures do not respond to first- and second-line anticonvulsant
drug (ACD) therapy.2-3 Little
is known about the clinical epidemiologic features of RSE, which may be because
of lack of consensus regarding its definition. Proposed criteria for RSE have
varied in the number of ACDs failed (2 drugs2, 4-7
or 3 drugs3, 8-10)
and in whether a minimum duration of persistent seizure activity is required
(range, none2, 7-10
to 1 hour5, 11 or 2 hours4, 6).
Estimates of the frequency of RSE in patients with SE have ranged from
9% to 40%,2-3,12
but few studies have focused specifically on RSE as a clinical problem, to
our knowledge. In one hospital series,12 failure
of first- and second-line therapy was associated with delayed treatment and
nonstructural causes of SE such as hypoxia-ischemia, metabolic encephalopathy,
and central nervous system infection. The results of the Veterans Affairs
(VA) Cooperative Study,13 a randomized trial
that compared 4 different first-line interventions for generalized convulsive
SE (GCSE), indicate that RSE may be a problem of greater magnitude than is
generally appreciated. In this trial,14 38%
of patients with "overt" SE and 82% of patients with "subtle" SE continued
to have seizures after receiving 2 ACDs, and only 2% and 5%, respectively,
stopped having seizures after receiving a third agent.
Many experts believe that SE should initially be treated with intravenous
lorazepam (0.1 mg/kg), followed by a loading dose of phenytoin or fosphenytoin
(20 mg/kg).8, 10 Although intravenous
phenobarbital (20 mg/kg) has conventionally been used as third-line therapy,
only a small percentage of patients will respond at this point. In the aforementioned
VA study,14 only 5% of patients with GCSE who
did not respond to lorazepam and phenytoin therapy responded to phenobarbital
administration. Accordingly, newer agents such as midazolam,3, 5-6,10, 15
propofol,4, 6 and intravenous valproic
acid16 have been recommended as reasonable
alternatives to phenobarbital for patients who do not respond to first- and
second-line therapy, but experience with their use is relatively limited.
Randomized controlled trials comparing treatment strategies for RSE have not
been performed to date, to our knowledge. To assess the feasibility of such
a study, we performed this retrospective analysis to (1) clarify how often
RSE is encountered in routine clinical practice, (2) identify risk factors
for RSE, and (3) evaluate clinical outcomes associated with RSE.
PATIENTS AND METHODS
STUDY POPULATION
We retrospectively identified all adults with SE admitted to the neurological
intensive care unit (NICU) at Columbia-Presbyterian Medical Center between
January 1, 1994, and March 31, 1998. Because of the retrospective nature of
this study, the need for written informed consent was waived by the hospital
institutional review board. Patients were identified using (1) the department
of neurology admission log; (2) the NICU admission log; and (3) a computerized
search of the hospital clinical information system for patients with a discharge
diagnosis of SE (International Classification of Diseases,
Ninth Revision, codes 345.2 and 345.3), partial seizures with decreased
level of consciousness (code 345.7), epilepsia partialis continua (code 345.7),
and convulsions (code 780.39). A complete list of all patients with possible
SE was compiled by cross-referencing the 3 sources.
The diagnosis of SE was established when either of the following criteria
was met: (1) continuous tonic-clonic or electrographic seizure activity for
at least 10 minutes or (2) intermittent seizure activity without recovery
of consciousness for at least 30 minutes. We equated these criteria because
continuous SE carries a worse prognosis than intermittent SE17
and because intermittent SE of more than 30 minutes' duration has a worse
prognosis than seizure episodes lasting 10 to 29 minutes.18
Using these criteria, we identified 132 hospital admissions for possible SE
in 122 patients. Medical records were retrieved for 85% of these episodes
(112/132), which were reviewed independently by 2 reviewers (J.L., F.M., L.J.D.,
or B.-F.F., and S.A.M.), with disagreements resolved by consensus. The diagnosis
of SE was confirmed in 85 hospital admissions. Because our goal was to determine
how often RSE occurs in patients who receive standard treatment for SE, we
excluded 2 episodes in which a benzodiazepine was not given, leaving 83 episodes
of SE in 74 patients for inclusion in the analysis.
SE DEFINITIONS
The primary cause of SE was classified as epilepsy related, structural
(ie, stroke or brain tumor), or nonstructural (ie, metabolic or hypoxic-ischemic
encephalopathy). Episodes of SE were classified as GCSE, nonconvulsive (NCSE),
and simple partial motor on the basis of clinical descriptions and electroencephalographic
(EEG) recordings. Generalized convulsive SE was considered present if any
of the following were described: generalized tonic-clonic seizures, grand
mal seizures, convulsions, bilateral rhythmic jerking, or similar descriptions.
If none of these were present, if the patient was stuporous or comatose, and
if the EEG showed ictal discharges, the seizures were considered nonconvulsive,
whether or not subtle movements (eg, facial twitching, tonic eye deviation,
and nystagmus) were observed. Periodic lateralized epileptiform discharges
(PLEDs) were not considered ictal discharges. In all cases, we noted whether
focal motor seizures (ie, lateralized tonic-clonic movements, head turning,
and eye deviation) were present at the onset of SE. If the precise onset of
seizures could not be determined, the onset of SE was judged to have occurred
when it was diagnosed. Refractory SE was defined as continuous or intermittent
seizures of at least 60 minutes' duration despite treatment with a benzodiazepine
(lorazepam or diazepam, any dose) and intravenous phenytoin, fosphenytoin,
or phenobarbital ( 10 mg/kg). We used ACD dosage criteria that are lower
than those recommended for treating SE (15-20 mg/kg) because a higher cutoff
value would have excluded many patients without RSE who responded to less
than full loading doses. Cessation of SE was defined as the last clinical
or electrographic seizure that occurred before becoming seizure free for at
least 72 hours; at least 1 EEG was performed to exclude ongoing nonconvulsive
seizures in patients with impaired unconsciousness after tonic-clonic activity
was controlled. Treatment failure was judged to have occurred if any clinical
or electrographic seizures occurred more than 1 hour after initiating first-,
second-, or third-line therapy.15
CLINICAL VARIABLES
Medical records were reviewed independently by 2 reviewers using a structured
data collection instrument. For each patient we recorded demographic information
(sex, age, race or ethnicity, and weight) and medical history (epilepsy, hypertension,
diabetes mellitus, coronary artery disease, and stroke). For each episode
of SE we recorded the clinical characteristics of SE (primary cause, seizure
classification, interval from onset to arrival at the emergency department,
and total duration); clinical variables on hospital admission (admission source,
previous ACD use, APACHE [Acute Physiology and Chronic Health Evaluation]
II score, worst Glasgow Coma Scale score, and maximum temperature within the
first 24 hours); laboratory test results (peak creatine kinase and serum glucose
levels, initial cerebrospinal fluid examination, and initial EEG); the dosage
and highest blood levels of all ACDs given during the first 24 hours of hospitalization;
hospital complications (fever [temperature >38.3°C], hypotension [systolic
blood pressure <100 mm Hg], respiratory failure treated with mechanical
ventilation, tachycardia [heart rate >120/min], pneumonia [fever or leukocytosis,
purulent sputum, and infiltrate on chest radiography], urinary tract infection
[positive culture findings], bacteremia [positive culture findings], hyperglycemia
[glucose level >240 mg/dL (>13.3 mmol/L)], and anemia treated with blood transfusion);
and outcome variables (Glasgow Outcome Scale score to assess functional status
before hospital admission and at discharge, hospital and NICU length of stay
[LOS], and cause of death).
STATISTICAL ANALYSIS
Statistics were analyzed using commercially available software (Statview
5.0; SAS Institute Inc, Cary, NC). Continuous values were compared using the
2-tailed t test or the Mann-Whitney test for nonnormally
distributed data. Categorical variables were compared using the Pearson  2 test or the Fisher exact test as appropriate. To identify independent
risk factors for RSE, clinical variables associated with RSE (P<.05) in a univariate analysis were entered into a backward stepwise
logistic regression model, with RSE as the dependent variable. Complications,
EEG findings, and outcome variables were analyzed separately as sequelae of
RSE. Because complications are more likely to occur as LOS increases, we examined
the relationship between RSE and specific complications while controlling
for LOS using multiple logistic regression, with each complication as the
dependent variable and RSE and hospital LOS as independent variables. Significance
was established at P<.05.
RESULTS
STUDY POPULATION
Mean age of the 74 patients with SE we studied was 63 years (range,
21-97 years); 44 (59%) were women. Thirty-one patients (42%) were black, 24
(32%) were white, and 19 (26%) were Hispanic. The most common comorbid conditions
were hypertension (n = 29, 39%), epilepsy (n = 28, 38%), stroke (n = 21, 28%),
diabetes mellitus (n = 21, 28%), and coronary artery disease (n = 16, 22%).
CLINICAL FEATURES OF SE
In 74 episodes (89%), the patient was admitted through the emergency
department, and in 9 (11%), the patient was transferred from another hospital.
The mean duration of seizures before emergency department admission was 1.3
hours (range, 0-4.25 hours). The most common causes of SE were low ACD levels
or a recent change in medication in patients with epilepsy (n = 26, 31%),
toxic metabolic encephalopathy (n = 16, 22%), stroke (n = 16, 22%), hypoxic-ischemic
encephalopathy (n = 7, 8%), refractory epilepsy (n = 5, 6%), brain tumor (n
= 4, 5%), and meningitis or encephalitis (n = 3, 4%).
TREATMENT RESPONSE OF SE
Seizures continued after treatment with a benzodiazepine in 57 (69%)
of the 83 SE episodes (Figure 1).
Fifty episodes (60%) were treated with diazepam; 15 (18%), diazepam and lorazepam;
13 (16%), lorazepam alone; and 5 (6%), midazolam alone or in combination with
other benzodiazepines. In 70 episodes (84%), phenytoin was given as the second-line
ACD; in 9 episodes (11%), phenobarbital was given; and in 4 episodes that
responded to benzodiazepines, no second agent was given. In 26 episodes (31%),
seizures persisted after administration of a second-line ACD; in all of these
cases, the total duration of SE exceeded 60 minutes, fulfilling our definition
of RSE. In only 1 of 26 RSE episodes did the patient receive less than 15
mg/kg of phenytoin.
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Figure 1. Flow chart showing the treatment
response of 83 episodes of status epilepticus (SE).
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TREATMENT RESPONSE OF RSE
Twenty-three of 26 episodes of RSE were treated with a third-line ACD
(Figure 2); 21 patients received
phenobarbital (mean dose, 10.3 mg/kg), and 1 each received valproic acid and
midazolam. Eleven patients (42%) had seizures for longer than 1 hour after
third-line therapy was initiated, and in 4 of these a fourth-line ACD was
given (midazolam, pentobarbital, valproic acid, and phenobarbital were given
to 1 patient each). All 4 of these patients experienced further seizures during
the following 72 hours.
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Figure 2. Flow chart showing the treatment
response of 26 episodes of refractory status epilepticus (RSE).
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RISK FACTORS FOR RSE
Univariate analysis showed that patients with RSE were significantly
less likely to have GCSE and more likely to have NCSE or focal motor seizures
at onset (Table 1). Patients with
RSE also had lower Glasgow Coma Scale scores and higher peak serum glucose
levels and received more phenytoin within the first 24 hours than patients
without RSE, although peak phenytoin levels were not different. In multivariate
analysis, NCSE (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.3-111.1; P = .03) and focal motor seizures at onset (OR, 3.1; 95%
CI, 1.1-9.1; P = .04) were identified as independent
risk factors for RSE.
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Table 1. Univariate Analysis of Clinical Factors Related to RSE*
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INITIAL EEG FINDINGS AND HOSPITAL COMPLICATIONS
Electroencephalography was performed in all patients with RSE and in
slightly more than half of those without RSE (Table 2). In all cases, the initial EEG was performed within 72
hours of hospital admission. Although interictal epileptiform activity and
electrographic seizures occurred more frequently after RSE, only PLEDs were
significantly associated with RSE.
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Table 2. Initial EEG Findings During Hospitalization*
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Respiratory failure treated with mechanical ventilation, fever, pneumonia,
hypotension, bacteremia, and anemia treated with blood transfusion each occurred
more often in patients with vs without RSE (Table 3). When controlling for LOS using multiple logistic regression,
all of these complications continued to show significant associations with
RSE except respiratory failure.
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Table 3. Complications During Hospitalization*
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CLINICAL OUTCOME
Mortality was higher in patients with vs without RSE (23% vs 14%), but
this difference was not significant (Table
4). Functional deterioration, reflected by a decreased Glasgow Outcome
Scale score from hospital admission to discharge, occurred significantly more
frequently in patients with RSE. Refractory SE was also associated with substantially
increased hospital and NICU LOS. Overall, most deaths resulted from overwhelming
medical complications. Of the 6 patients with RSE who did not survive, only
2 had uncontrolled seizures at the time of death.
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Table 4. Clinical Outcome*
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COMMENT
In this study of patients in the NICU treated for SE, 31% of the episodes
were refractory to first- and second-line ACD therapy. Nonconvulsive SE and
focal motor seizures at onset were independent risk factors for RSE, and PLEDs
occurred more frequently on initial EEG. Although the mortality rate was not
increased, RSE was associated with more frequent medical complications, longer
NICU and hospital LOS, and increased functional disability at discharge. More
than 40% of patients with RSE had seizures after a third-line ACD was given,
and the median duration of refractory status was 20 hours. Randomized controlled
trials are needed to identify more effective treatments for RSE and to improve
outcomes for these patients.
Our study population differs from other hospital-based series of SE12, 19-20 in that alcohol withdrawal
was an uncommon cause of SE and because women outnumbered men. Ninety percent
of our patients were admitted to the hospital via the emergency department,
with a mean duration of seizures before admission of 1.3 hours. Only 31% stopped
having seizures after first-line benzodiazepine treatment (diazepam alone
or in combination with another agent in 78% of episodes; mean dose, 0.2 mg/kg),
reflecting the prevailing practice at that time.12
The period we studied predated the VA Cooperative Study,13
which has since established that lorazepam, 0.1 mg/kg, is at least as effective
as other first-line treatments for SE. The clinical response rate to lorazepam
therapy in the VA study was 51%, but comparison of their results with ours
is hampered since we used lower doses of ACDs in general, treated a smaller
proportion of patients with NCSE, and used a more stringent criterion to define
the cessation of SE (no recurrent seizures for 72 hours vs 40 minutes).
The frequency of RSE (>60 minutes of seizure activity despite treatment
with 2 intravenous ACDs) was 31%. This percentage is somewhat lower than the
40% reported for patients with GCSE at San Francisco General Hospital in the
1980s.12 In our study, the frequency of RSE
was substantially higher in patients with NCSE (88% [7/8]) than in those with
GCSE (26% [19/74]). This finding is consistent with the VA Cooperative Study,13 in which RSE occurred in 82% of patients with subtle
SE (coma and ictal discharges on EEG, with or without subtle convulsive movements)
compared with 38% of patients with overt SE (2 generalized convulsions).
Except for primary generalized NCSE (absence status, petit mal status, or
"spike wave stupor"), which occurs exclusively in patients with idiopathic
epilepsy and generally responds well to treatment,21
these findings confirm that NCSE is much more likely to be refractory than
is GCSE. Although the association of complex partial and subtle secondary
generalized NCSE with a high risk of mortality is well established,22-23 it remains to be seen whether aggressive
treatment with continuous-infusion ACDs improves clinical outcomes, particularly
in the elderly.23-24
Fifty-eight percent (15/26) of our patients with RSE had no further
seizures after receiving additional phenytoin or a third-line agent, which
in most cases was phenobarbital. By contrast, only 5.3% of patients with GCSE
in the VA Cooperative Study14 responded to
phenobarbital administration after failing to respond to lorazepam and phenytoin
therapy. This discrepancy probably reflects the fact that patients in the
VA study were more refractory in that they had a longer median duration of
SE before treatment, had already received higher doses of first- and second-line
ACDs, and had a higher frequency of hypoxic-ischemic encephalopathy than our
study population.
In multivariate analysis, we identified NCSE and focal motor seizures
at onset (which occurred in patients with NCSE and patients with GCSE) as
independent risk factors for RSE. One possible interpretation of this finding
is that in contrast to seizures that rapidly generalize and spontaneously
abate, repetitive or continuous seizures that do not readily generalize may
be associated with more severe underlying brain pathology and hence may be
more refractory to therapy. Another possible explanation is that a substantial
proportion of our patients with GCSE may have had generalized-onset seizures,
which tend to be more responsive to treatment than secondary generalized seizures.25 Although we did not determine how many of our patients
with GCSE had generalized-onset seizures because of incomplete EEG data, they
have constituted 20% to 40% of GCSE in other series.1, 20
Factors not associated with RSE included the cause of seizures, the duration
of seizures before treatment, APACHE II scores, and body temperature. Although
patients with RSE received significantly more phenytoin than patients without
RSE, there was no difference in peak 24-hour blood levels, which might be
explained by larger volumes of distribution or increased hepatic metabolism
in patients with RSE.
Periodic lateralized epileptiform discharges are EEG discharges characterized
by a spike or sharp wave followed by a slow wave that occurs every 1 to 2
seconds. They may occur in patients with acute focal brain injury in the absence
of seizures, but they also appear frequently in the aftermath of prolonged,
untreated seizures26 and have been associated
with poor outcome in SE.27-28
Accordingly, the association of PLEDs with RSE in our study most likely reflects
the longer duration of SE in these patients (Table 4). The clinical significance of PLEDs after SE is controversial;
opinions differ on whether they represent a benign postictal phenomenon or
harmful "agonal" ictal discharges that require treatment.26
Persistent electrographic seizures have been reported in 15% of treated patients
after the cessation of clinical SE23 and are
associated with poor prognosis.27 Although
nearly 30% (17/57) of our subjects had ictal discharges on initial EEG (Table 2), we were retrospectively unable
to determine how many of these subjects had stopped having seizures clinically
at this point.
Even after controlling for hospital LOS, RSE was associated with several
serious medical complications, including fever, pneumonia, hypotension, bacteremia,
and anemia treated with blood transfusions. Refractory SE was also associated
with increased hospital and NICU LOS and more frequent functional deterioration
at discharge, defined as a decrease in the Glasgow Outcome Scale score from
admission to discharge. Morbidity after SE may result from neurological deficits
caused by acute brain disease or seizures or from physical deconditioning
related to secondary medical complications and prolonged hospitalization.
In a separate analysis of this study cohort, we found that morbidity was predicted
by acute symptomatic causes of SE and by prolonged LOS.29
Given the poor treatment response and morbidity rate associated with
RSE, better treatment strategies are needed. The most reasonable options for
third-line therapy after failure of lorazepam and phenytoin include intravenous
phenobarbital or valproic acid or continuous-infusion therapy with midazolam
or propofol. Treatment practices for RSE vary widely, and only small, nonrandomized
cohort studies have directly compared therapies for RSE.4, 6
Prospective randomized controlled trials are needed to define the optimal
treatment of refractory GCSE and NCSE.
AUTHOR INFORMATION
Accepted for publication August 21, 2001.
Author contributions: Conception and design (Drs Mayer, Claassen, and Lokin and Ms Mendelsohn); acquisition
of data (Drs Mayer, Fitzsimmons, and Dennis and Ms Mendelsohn); analysis and interpretation of data (Drs Mayer and
Claassen); drafting of the manuscript (Drs Mayer
and Claassen); critical revision of the manuscript for important intellectual
content (Drs Claassen, Fitzsimmons, and Dennis and Ms Mendelsohn); statistical expertise (Drs Mayer and Claassen); administrative, technical, or material support (Drs Lokin and Dennis and Ms Mendelsohn); supervision (Drs Mayer and Fitzsimmons).
We thank Lawrence J. Hirsch, MD, and W. Allen Hauser, MD, of the Comprehensive
Epilepsy Center at Columbia University, for thoughtful input regarding our
analysis and for critical review of the manuscript.
Corresponding author and reprints: Stephan A. Mayer, MD, Division
of Critical Care Neurology, Neurological Institute, 710 W 168th St, Unit 39,
New York, NY 10032 (e-mail: sam14{at}columbia.edu).
From the Division of Critical Care Neurology, Department of Neurology,
College of Physicians and Surgeons of Columbia University, New York, NY.
REFERENCES
| |
1. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus
in Richmond, Virginia. Neurology. 1996;46:1029-1035.
FREE FULL TEXT
2. Jagoda A, Riggio S. Refractory status epilepticus in adults. Ann Emerg Med. 1993;22:1337-1348.
FULL TEXT
|
ISI
| PUBMED
3. Bleck TP. Advances in the management of refractory status epilepticus. Crit Care Med. 1993;21:955-957.
ISI
| PUBMED
4. Stecker MM, Kramer TH, Raps EC, O'Meeghan R, Dulaney E, Skaar DJ. Treatment of refractory status epilepticus with propofol. Epilepsia. 1998;39:18-26.
FULL TEXT
|
ISI
| PUBMED
5. Hanley DF, Kross JF. Use of midazolam in the treatment of refractory status epilepticus. Clin Ther. 1998;20:1093-1105.
FULL TEXT
|
ISI
| PUBMED
6. Prasad A, Worrall BB, Bertram EH, Bleck TP. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia. 2001;42:380-386.
FULL TEXT
|
ISI
| PUBMED
7. Gilbert DL, Gartside PS, Glauser TA. Efficacy and mortality in treatment of refractory generalized convulsive
status epilepticus in children: a meta-analysis. J Child Neurol. 1999;14:602-609.
FREE FULL TEXT
8. Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. JAMA. 1993;270:854-859.
FREE FULL TEXT
9. Cascino GD. Generalized convulsive status epilepticus. Mayo Clin Proc. 1996;71:787-792.
ABSTRACT
10. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998;338:970-976.
FREE FULL TEXT
11. Maytall J. The management of status epilepticus in children. Child Hosp Q. 1991;3:255-263.
12. Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. 1993;43:483-488.
FREE FULL TEXT
13. Treiman DM, Meyers PD, Walton NY, et al for the Veterans Affairs Status Epilepticus Cooperative Study Group. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med. 1998;339:792-798.
FREE FULL TEXT
14. Treiman DM, Walton NY, Collins JF, Point P. Treatment of status epilepticus if first drug fails [abstract]. Epilepsia. 1999;40(suppl 7):243.
15. Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA. Continuous EEG monitoring and midazolam infusion for refractory status
epilepticus. Neurology. 2001;57:1036-1042.
FREE FULL TEXT
16. Sinha S, Naritoku DK. Intravenous valproate is well tolerated in unstable patients with status
epilepticus. Neurology. 2000;55:722-724.
FREE FULL TEXT
17. Waterhouse EJ, Garnett LK, Towne AR, et al. Prospective population-based study of intermittent and continuous convulsive
status epilepticus in Richmond, Virginia. Epilepsia. 1999;40:752-758.
FULL TEXT
|
ISI
| PUBMED
18. DeLorenzo RJ, Garnett LK, Towne AR, et al. Comparison of status epilepticus with prolonged seizure episodes lasting
from 10 to 29 minutes. Epilepsia. 1999;40:164-169.
FULL TEXT
|
ISI
| PUBMED
19. Aminoff MJ, Simon RP. Status epilepticus. Am J Med. 1980;69:657-666.
FULL TEXT
|
ISI
| PUBMED
20. Barry E, Hauser WA. Status epilepticus: the interaction of epilepsy and acute brain disease. Neurology. 1993;43:1473-1478.
FREE FULL TEXT
21. Guberman A, Cantu-Reyna G, Stuss D, Broughton R. Nonconvulsive generalized status epilepticus. Neurology. 1986;36:1284-1291.
FREE FULL TEXT
22. Krumholz A, Sung GY, Fisher RS, Barry E, Bergey GK, Grattan LM. Complex partial status epilepticus accompanied by serious morbidity
and mortality. Neurology. 1995;45:1499-1504.
FREE FULL TEXT
23. DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive
status epilepticus. Epilepsia. 1998;39:833-840.
FULL TEXT
|
ISI
| PUBMED
24. Litt B, Wityk RJ, Hertz SH, et al. Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia. 1998;39:1194-1202.
FULL TEXT
|
ISI
| PUBMED
25. Cascino GD. Generalized convulsive status epilepticus. Mayo Clin Proc. 1996;71:787-792.
26. Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol. 1995;12:343-362.
ISI
| PUBMED
27. Jaitly R, Sgro JA, Towne AR, Ko D, DeLorenzo RJ. Prognostic value of EEG monitoring after status epilepticus: a prospective adult study. J Clin Neurophysiol. 1997;14:326-334.
ISI
| PUBMED
28. Nei M, Lee J-M, Shanker VL, Sperling MR. The EEG and prognosis in status epilepticus. Epilepsia. 1999;40:157-163.
FULL TEXT
|
ISI
| PUBMED
29. Claassen J, Lokin JK, Fitzsimmons B-FM, Mendelsohn FA, Mayer SA. Predictors of functional disability and mortality after status epilepticus. Neurology. 2002;58:139-142.
FREE FULL TEXT
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Yoong et al.
EDUCATION AND PRACTICE 2009;94:1-9.
FULL TEXT
The Howling Cortex: Seizures and General Anesthetic Drugs
Voss et al.
Anesth. Analg. 2008;107:1689-1703.
ABSTRACT
| FULL TEXT
Treatment of Acute Seizures and Status Epilepticus
Costello and Cole
J Intensive Care Med 2007;22:319-347.
ABSTRACT
Generalised convulsive status epilepticus: an overview
Nandhagopal
Postgrad. Med. J. 2006;82:723-732.
ABSTRACT
| FULL TEXT
A clinical score for prognosis of status epilepticus in adults
Rossetti et al.
Neurology 2006;66:1736-1738.
ABSTRACT
| FULL TEXT
Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation
Rossetti et al.
J. Neurol. Neurosurg. Psychiatry 2006;77:611-615.
ABSTRACT
| FULL TEXT
Refractory Status Epilepticus: Effect of Treatment Aggressiveness on Prognosis
Rossetti et al.
Arch Neurol 2005;62:1698-1702.
ABSTRACT
| FULL TEXT
Status epilepticus: an evidence based guide
Walker
BMJ 2005;331:673-677.
FULL TEXT
A "Malignant" Variant of Status Epilepticus
Holtkamp et al.
Arch Neurol 2005;62:1428-1431.
ABSTRACT
| FULL TEXT
Status Epilepticus Increases the Intracellular Accumulation of GABAA Receptors
Goodkin et al.
J. Neurosci. 2005;25:5511-5520.
ABSTRACT
| FULL TEXT
Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit
Holtkamp et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:534-539.
ABSTRACT
| FULL TEXT
Pediatric Refractory Partial Status Epilepticus Responsive to Topiramate
Blumkin et al.
J Child Neurol 2005;20:239-241.
ABSTRACT
Creutzfeldt-Jakob Disease Presenting as Refractory Nonconvulsive Status Epilepticus
Shapiro et al.
J Intensive Care Med 2004;19:345-348.
ABSTRACT
The Management of Status Epilepticus
Marik and Varon
Chest 2004;126:582-591.
ABSTRACT
| FULL TEXT
Treatment of Refractory Status Epilepticus With Inhalational Anesthetic Agents Isoflurane and Desflurane
Mirsattari et al.
Arch Neurol 2004;61:1254-1259.
ABSTRACT
| FULL TEXT
Detection of electrographic seizures with continuous EEG monitoring in critically ill patients
Claassen et al.
Neurology 2004;62:1743-1748.
ABSTRACT
| FULL TEXT
Assessment of acute morbidity and mortality in nonconvulsive status epilepticus
Shneker and Fountain
Neurology 2003;61:1066-1073.
ABSTRACT
| FULL TEXT
The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists
Holtkamp et al.
J. Neurol. Neurosurg. Psychiatry 2003;74:1095-1099.
ABSTRACT
| FULL TEXT
New Management Strategies in the Treatment of Status Epilepticus
Manno
Mayo Clin Proc. 2003;78:508-518.
ABSTRACT
More Data on Treatment Response of Refractory SE
JWatch Neurology 2002;2002:9-9.
FULL TEXT
Refractory Status Epilepticus in 2001
Bleck
Arch Neurol 2002;59:188-189.
FULL TEXT
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