- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00641563
Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)
October 13, 2011 updated by: University Hospital Inselspital, Berne
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
10
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Bern, Switzerland, 3010
- Departement of Intensive Care Medicine - University Hospital Bern - Inselspital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 40 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- age 18 years and older
- healthy
Exclusion Criteria:
- History of problems during anesthesia
- Impairment of the auditory system
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
Infusion of dexmedetomidine
Midazolam infusion
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
|
Infusion of dexmedetomidine
Midazolam infusion
Infusion of remifentanil
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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
Time Frame: 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)
|
awake + 3 sedation levels (RS2/3/4) (20 minutes each)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Matthias Haenggi, MD, University of Bern
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2004
Primary Completion (Actual)
June 1, 2004
Study Completion (Actual)
June 1, 2004
Study Registration Dates
First Submitted
February 25, 2008
First Submitted That Met QC Criteria
March 21, 2008
First Posted (Estimate)
March 24, 2008
Study Record Updates
Last Update Posted (Estimate)
November 22, 2011
Last Update Submitted That Met QC Criteria
October 13, 2011
Last Verified
October 1, 2011
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Analgesics, Non-Narcotic
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Analgesics, Opioid
- Narcotics
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Remifentanil
- Midazolam
- Dexmedetomidine
Other Study ID Numbers
- KIM-NMP3
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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