Status Epilepticus
Conditions
Keywords
Refractory status epilepticus,, coma-induction,, treatment,, propofol,, barbiturates,, efficacy,, safety.
Brief summary
The purpose of this study is to determine whether propofol or barbiturates should be preferred in the treatment of status epilepticus (continuous seizure activity) refractory to 2 standard antiepileptic agents.
Detailed description
Refractory status epilepticus (SE) develops in 31%-44% of patients with SE, with a mortality of 16%-23%. Coma induction is advocated for its management. Propofol and barbiturates are the most used agents, but no comparative study has been performed. In consideration of the uncertainty regarding the relative effectiveness, despite several retrospective data, a prospective investigation is needed. The objective is to assess the effectiveness (SE control, adverse events) of a first course of propofol versus barbiturates in the treatment of refractory SE, in adults with refractory SE not due to cerebral anoxia. Comparison: Coma induction with standardized doses of propofol or barbiturates titrated towards burst-suppression on EEG, then assessment of the proportion of patients achieving a control of SE.
Interventions
DRUGpropofol
liquid, mg/kg.h, titrated after EEG
DRUGthiopental/pentobarbital
liquid, mg/kg.h, titrated after EEG
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with refractory status epilepticus not due to cerebral anoxia, needing coma induction for clinical management.
Exclusion criteria
* Age \< 16 years old. * Known pregnancy. * Cerebral anoxia as SE etiology. * Epilepsia partialis continua (simple partial SE). * Known intolerance to the study drugs. * Known mitochondrial disorder, hyperlipidemia, or significant rhabdomyolysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Refractory Status Epilepticus Controlled With First Course of Study Drug | after return of continuous EEG activity (typically after 36 hours - 5 days) | Control of status epilepticus refractory to benzodiazepines and a first antiepileptic drug after administration of the study drug; dichotomous assessment (yes/no) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome at Day 21 | 21 days | Return to baseline clinical conditions (i.e.: no new handicap, no death) |
| Patients With Infectious Complications Requiring Specific Treatment | 10 days | — |
| Patients With Hypotension Requiring Specific Treatment | 10 days | — |
| Patients With Propofol Infusion Syndrome | 10 days | Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides. |
| Intubation Time in Survivors | Up to 3 months | — |
Countries
Switzerland, United States
Participant flow
Recruitment details
Rcruitment in participating centers took part between 2006 and 2010.
Participants by arm
| Arm | Count |
|---|---|
| Propofol titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG) | 14 |
| Thiopental/Pentobarbital titrated to electroencephalographic burst-suppression (intravenous load as per protocol, then following the EEG) | 9 |
| Total | 23 |
Baseline characteristics
| Characteristic | Propofol | Thiopental/Pentobarbital | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 4 Participants | 13 Participants |
| Region of Enrollment Switzerland | 9 participants | 7 participants | 16 participants |
| Region of Enrollment United States | 5 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 9 |
| serious Total, serious adverse events | 1 / 14 | 1 / 9 |
Outcome results
Primary
Refractory Status Epilepticus Controlled With First Course of Study Drug
Control of status epilepticus refractory to benzodiazepines and a first antiepileptic drug after administration of the study drug; dichotomous assessment (yes/no)
Time frame: after return of continuous EEG activity (typically after 36 hours - 5 days)
Population: Number of patients fulfilling primary outcome criteria
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Refractory Status Epilepticus Controlled With First Course of Study Drug | 6 participants |
| Thiopental/Pentobarbital | Refractory Status Epilepticus Controlled With First Course of Study Drug | 2 participants |
p-value: 0.4Fisher Exact
Secondary
Clinical Outcome at Day 21
Return to baseline clinical conditions (i.e.: no new handicap, no death)
Time frame: 21 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Clinical Outcome at Day 21 | 5 participants |
| Thiopental/Pentobarbital | Clinical Outcome at Day 21 | 3 participants |
p-value: 1Fisher Exact
Secondary
Intubation Time in Survivors
Time frame: Up to 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Propofol | Intubation Time in Survivors | 4 days |
| Thiopental/Pentobarbital | Intubation Time in Survivors | 13.5 days |
p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
Patients With Hypotension Requiring Specific Treatment
Time frame: 10 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Patients With Hypotension Requiring Specific Treatment | 7 participants |
| Thiopental/Pentobarbital | Patients With Hypotension Requiring Specific Treatment | 5 participants |
p-value: 1Fisher Exact
Secondary
Patients With Infectious Complications Requiring Specific Treatment
Time frame: 10 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Patients With Infectious Complications Requiring Specific Treatment | 7 participants |
| Thiopental/Pentobarbital | Patients With Infectious Complications Requiring Specific Treatment | 6 participants |
p-value: 0.67Fisher Exact
Secondary
Patients With Propofol Infusion Syndrome
Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides.
Time frame: 10 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Propofol | Patients With Propofol Infusion Syndrome | 1 participants |
| Thiopental/Pentobarbital | Patients With Propofol Infusion Syndrome | 0 participants |