Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Dex/Remi followed by Mida/Remi Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week |
Drug: Dexmedetomidine
Infusion of dexmedetomidine
Drug: Midazolam
Midazolam infusion
Drug: Remifentanil
Infusion of remifentanil
|
| Active Comparator: Mida/Remi followed by Dexa/Remi Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week |
Drug: Dexmedetomidine
Infusion of dexmedetomidine
Drug: Midazolam
Midazolam infusion
Drug: Remifentanil
Infusion of remifentanil
|
Outcome Measures
Primary Outcome Measures
- 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 [awake + 3 sedation levels (RS2/3/4) (20 minutes each)]
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)
Secondary Outcome Measures
- BIS-Index Awake and 3 Sedation Levels (RS 2/3/4) [awake and 3 sedation levels (RS 2/3/4) 20 min each]
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.)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
age 18 years and older
-
healthy
Exclusion Criteria:
-
History of problems during anesthesia
-
Impairment of the auditory system
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Departement of Intensive Care Medicine - University Hospital Bern - Inselspital | Bern | Switzerland | 3010 |
Sponsors and Collaborators
- University Hospital Inselspital, Berne
- GE Healthcare
Investigators
- Principal Investigator: Matthias Haenggi, MD, University of Bern
Study Documents (Full-Text)
None provided.More Information
Publications
- KIM-NMP3
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dex/Remi Followed by Mida/Remi | Mida/Remi Followed by Dex/Remi |
|---|---|---|
| Arm/Group Description | Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week | Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week |
| Period Title: Infusion 1 | ||
| STARTED | 5 | 5 |
| COMPLETED | 5 | 5 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Infusion 1 | ||
| STARTED | 5 | 5 |
| COMPLETED | 5 | 5 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | Both arms combined |
| Overall Participants | 10 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
10
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
24
(3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
10
100%
|
| Region of Enrollment (participants) [Number] | |
| Switzerland |
10
100%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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) |
| Time Frame | awake + 3 sedation levels (RS2/3/4) (20 minutes each) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dex/Remi | Mida/Remi |
|---|---|---|
| Arm/Group Description | Sedation with dexmedetomidine and remifentanil | Sedation with midazolam and remifentanil |
| Measure Participants | 10 | 10 |
| awake |
-5.9
(1.3)
|
-5.3
(1.3)
|
| RS 2 |
-6.4
(1.1)
|
-4.8
(2)
|
| RS 3 |
-4.7
(2.4)
|
-2.4
(2)
|
| RS 4 |
-3.5
(2.7)
|
-0.4
(1.1)
|
| Title | BIS-Index Awake and 3 Sedation Levels (RS 2/3/4) |
|---|---|
| Description | 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.) |
| Time Frame | awake and 3 sedation levels (RS 2/3/4) 20 min each |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dex/Remi | Mida/Remi |
|---|---|---|
| Arm/Group Description | Sedation with dexmedetomidine and remifentanil | Sedation with midazolam and remifentanil |
| Measure Participants | 10 | 10 |
| awake |
92.5
(4.64)
|
93.7
(3.51)
|
| sedation level RS 2 |
84.5
(5.82)
|
84.7
(5.13)
|
| sedation level RS 3 |
69.5
(8.05)
|
73.2
(6.66)
|
| sedation level RS 4 |
51.4
(7.16)
|
68.9
(5.70)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Dex/Remi | Mida/Remi Followed by Dex/Remi | ||
| Arm/Group Description | Sedation with dexmedetomidine and remifentanil | Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week | ||
All Cause Mortality |
||||
| Dex/Remi | Mida/Remi Followed by Dex/Remi | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Dex/Remi | Mida/Remi Followed by Dex/Remi | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Dex/Remi | Mida/Remi Followed by Dex/Remi | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. M. Hänggi |
|---|---|
| Organization | University Hospital Bern, Switzerland |
| Phone | 0316323029 |
| matthias.haenggi@insel.ch |
- KIM-NMP3