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| Name | Class |
|---|---|
| GE Healthcare | INDUSTRY |
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Sedation may be necessary in intensive care to facilitate diverse therapeutic interventions, but the use of sedative drugs may increase the risk of delirium and long-term cognitive impairment. Thus the implementation and monitoring of sedation remains difficult despite the use of sedation protocols and clinical sedation scores. Attempts to improve sedation monitoring through the use of the electroencephalogram(EEG) have been disappointing. Derived variables based on the unstimulated EEG fail to predict the response to external stimuli at the clinically most relevant light-to-moderate sedation levels, and the overlap between moderate and deep sedation levels is wide. We have demonstrated that long-latency auditory evoked potentials (ERPs)can be used to avoid deep levels of sedation in healthy volunteers during propofol sedation, independent of the concomitant administration of remifentanil. This approach has a potential clinical application for improved monitoring of sedation. Since the effects of different sedative drugs on the EEG may vary widely, the use of ERPs to monitor sedation needs to be evaluated with different sedative drugs. Therefore we will administer two widely used drug combinations (dexmedetomidine/remifentanil and midazolam/remifentanil) in healthy volunteers and record ERPS and processed EEG during clinical relevant sedation levels
Sedation may be necessary in intensive care to facilitate diverse therapeutic interventions, but the use of sedative drugs may increase the risk of delirium and long-term cognitive impairment. Thus the implementation and monitoring of sedation remains difficult despite the use of sedation protocols and clinical sedation scores. Attempts to improve sedation monitoring through the use of the electroencephalogram (EEG) have been disappointing. Derived variables based on the unstimulated EEG fail to predict the response to external stimuli at the clinically most relevant light-to-moderate sedation levels, and the overlap between moderate and deep sedation levels is wide. We have demonstrated that long-latency auditory evoked potentials (ERPs)can be used to avoid deep levels of sedation in healthy volunteers during propofol sedation, independent of the concomitant administration of remifentanil. This approach has a potential clinical application for improved monitoring of sedation. Since the effects of different sedative drugs on the EEG may vary widely, the use of ERPs to monitor sedation needs to be evaluated with different sedative drugs. The alpha-2 agonist dexmedetomidine (dex) has been approved for short-term sedation in surgical intensive care unit (ICU) patients. Preliminary data suggest that the risk of delirium may be substantially reduced when dexmedetomidine is used to produce sedation. Since dexmedetomidine acts via different receptors and brain areas than do benzodiazepines and propofol, its impact on the brain electrophysiology may also be different. The assessment of dexmedetomidine's effects on the EEG and ERPs at various sedation levels has been limited in humans. We hypothesized that the combinations DEXMEDETOMIDINE/REMIFANTANIL (dex/remi) and MIDAZOLAM/REMIFENTANIL (mida/remi) would induce the same changes in EEG and long-latency ERPs during light-to-moderate levels of sedation in healthy subjects, despite the different quality of sedation that they provide. The opioid remifentanil was added because virtually all patients in the ICU have some level of pain and receive an opioid analgesic in combination with a sedative. 10 healthy subjects were assessed with both drug combinations (dex/remi and mida/remi), at least 7 days apart. The sequence of the drug combinations were randomized.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dex/Remi followed by Mida/Remi | Active Comparator | Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week |
|
| Mida/Remi followed by Dexa/Remi | Active Comparator | Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | Infusion of dexmedetomidine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Amplitudes (in Micro Volts) of Acoustic Event Related Potentials (Time-locked Amplitudes in the Electroencephalogram 100 Milliseconds After the Acoustic Stimulus, Averaged Over 40 Stimuli)Awake and at 3 Different Drug-induced Sedation Levels | Event Related Potentials (time-locked amplitudes in the electroencephalogram 100 milliseconds after the acoustic stimulus, averaged over 40 stimuli) Sedation levels were graded with the Ramsay scale (RS), where the responses of patients to standardized increasing stimuli (voice, then prodding, the pain stimulus) are graded. The higher the number, the deeper is the sedation. RS 6 means no response at all (= anesthesia) | awake + 3 sedation levels (RS2/3/4) (20 minutes each) |
| Measure | Description | Time Frame |
|---|---|---|
| BIS-Index Awake and 3 Sedation Levels (RS 2/3/4) | BIS-Index is a dimensionless value ranging from 0-100, indicating fully awake at 100 and a flat-line electroencephalogram at 0. Standard anesthesia creates a BIS-Index range 40-60. The scale is ordinal, not interval. BIS Index is calculated from the EEG by a proprietary algorithm (Aspect Medical Inc.) | awake and 3 sedation levels (RS 2/3/4) 20 min each |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthias Haenggi, MD | University of Bern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Departement of Intensive Care Medicine - University Hospital Bern - Inselspital | Bern | 3010 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15562062 | Background | Haenggi M, Ypparila H, Takala J, Korhonen I, Luginbuhl M, Petersen-Felix S, Jakob SM. Measuring depth of sedation with auditory evoked potentials during controlled infusion of propofol and remifentanil in healthy volunteers. Anesth Analg. 2004 Dec;99(6):1728-1736. doi: 10.1213/01.ANE.0000135634.46493.0A. | |
| 17056949 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dex/Remi Followed by Mida/Remi | Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week |
| FG001 | Mida/Remi Followed by Dex/Remi | Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Infusion 1 |
| |||||||||||||
| Infusion 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Both arms combined |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Amplitudes (in Micro Volts) of Acoustic Event Related Potentials (Time-locked Amplitudes in the Electroencephalogram 100 Milliseconds After the Acoustic Stimulus, Averaged Over 40 Stimuli)Awake and at 3 Different Drug-induced Sedation Levels | Event Related Potentials (time-locked amplitudes in the electroencephalogram 100 milliseconds after the acoustic stimulus, averaged over 40 stimuli) Sedation levels were graded with the Ramsay scale (RS), where the responses of patients to standardized increasing stimuli (voice, then prodding, the pain stimulus) are graded. The higher the number, the deeper is the sedation. RS 6 means no response at all (= anesthesia) | Posted | Mean | Standard Deviation | micro Volt | awake + 3 sedation levels (RS2/3/4) (20 minutes each) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dex/Remi | Sedation with dexmedetomidine and remifentanil |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. M. Hänggi | University Hospital Bern, Switzerland | 0316323029 | matthias.haenggi@insel.ch |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D008874 | Midazolam |
| D000077208 | Remifentanil |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Midazolam | Drug | Midazolam infusion |
|
| Remifentanil | Drug | Infusion of remifentanil |
|
| Haenggi M, Ypparila H, Hauser K, Caviezel C, Korhonen I, Takala J, Jakob SM. The effects of dexmedetomidine/remifentanil and midazolam/remifentanil on auditory-evoked potentials and electroencephalogram at light-to-moderate sedation levels in healthy subjects. Anesth Analg. 2006 Nov;103(5):1163-9. doi: 10.1213/01.ane.0000237394.21087.85. |
| 19228415 | Result | Haenggi M, Ypparila-Wolters H, Hauser K, Caviezel C, Takala J, Korhonen I, Jakob SM. Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study. Crit Care. 2009;13(1):R20. doi: 10.1186/cc7723. Epub 2009 Feb 19. |
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|
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mida/Remi |
Sedation with midazolam and remifentanil |
|
|
| Secondary | BIS-Index Awake and 3 Sedation Levels (RS 2/3/4) | BIS-Index is a dimensionless value ranging from 0-100, indicating fully awake at 100 and a flat-line electroencephalogram at 0. Standard anesthesia creates a BIS-Index range 40-60. The scale is ordinal, not interval. BIS Index is calculated from the EEG by a proprietary algorithm (Aspect Medical Inc.) | Posted | Mean | Standard Deviation | Units on a scale | awake and 3 sedation levels (RS 2/3/4) 20 min each |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Mida/Remi Followed by Dex/Remi | Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week | 0 | 10 | 0 | 10 |
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| D001569 |
| Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| sedation level RS 3 |
|
| sedation level RS 4 |
|