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Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)

This study has been completed.
Sponsor:
Collaborator:
GE Healthcare
Information provided by:
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT00641563
First received: February 25, 2008
Last updated: October 13, 2011
Last verified: October 2011

February 25, 2008
October 13, 2011
March 2004
June 2004   (final data collection date for primary outcome measure)
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 [ Time Frame: awake + 3 sedation levels (RS2/3/4) (20 minutes each) ] [ Designated as safety issue: No ]
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)
Amplitudes of acoustic Event Related Potentials [ Time Frame: all sedation levels (awake + 3 sedation levels RS2/3/4) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00641563 on ClinicalTrials.gov Archive Site
BIS-Index Awake and 3 Sedation Levels (RS 2/3/4) [ Time Frame: awake and 3 sedation levels (RS 2/3/4) 20 min each ] [ Designated as safety issue: No ]
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.)
  • BIS-Index [ Time Frame: awake and 3 sedation levels ] [ Designated as safety issue: No ]
  • Entropy (State Entropy and Response Entropy) [ Time Frame: awake and 3 sedation levels ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)
The Effects of Dexmedetomidine/Remifentanil and Midazolam/Remifentanil on Auditory-evoked Potentials and Electroencephalogram at Light-to-moderate Sedation Levels in Healthy Subjects

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Conscious Sedation
  • Deep Sedation
  • Critical Care
  • Drug: Dexmedetomidine
    Infusion of dexmedetomidine
  • Drug: Midazolam
    Midazolam infusion
  • Drug: Remifentanil
    Infusion of remifentanil
  • Active Comparator: Dex/Remi followed by Mida/Remi
    Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week
    Interventions:
    • Drug: Dexmedetomidine
    • Drug: Midazolam
    • Drug: 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
    Interventions:
    • Drug: Dexmedetomidine
    • Drug: Midazolam
    • Drug: Remifentanil

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
June 2004
June 2004   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • age 18 years and older
  • healthy

Exclusion Criteria:

  • History of problems during anesthesia
  • Impairment of the auditory system
Male
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT00641563
KIM-NMP3
No
Matthias Haenggi, Department of Intensive Care Medicine, university Hospital Bern - Inselspital
University Hospital Inselspital, Berne
GE Healthcare
Principal Investigator: Matthias Haenggi, MD University of Bern
University Hospital Inselspital, Berne
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP