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Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)
This study has been completed.
First Received: February 25, 2008   Last Updated: March 21, 2008   History of Changes
Sponsors and Collaborators: University Hospital Inselspital, Berne
GE Healthcare
Information provided by: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT00641563
  Purpose

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 Intervention
Conscious Sedation
Deep Sedation
Critical Care
Device: Measurement of auditory ERPS (event related potentials) during sedation

Study Type: Interventional
Study Design: Basic Science, Open Label, Active Control, Factorial Assignment
Official Title: The Effects of Dexmedetomidine/Remifentanil and Midazolam/Remifentanil on Auditory-Evoked Potentials and Electroencephalogram at Light-to-Moderate Sedation Levels in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Amplitudes of acoustic Event Related Potentials [ Time Frame: all sedation levels (awake + 3 sedation levels RS2/3/4) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: March 2004
Study Completion Date: June 2004
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Dex/Remi: Active Comparator
Sedation with dexmedetomidine and remifentanil
Device: Measurement of auditory ERPS (event related potentials) during sedation
Measurement of the amplitudes of auditory event related potentials (time locked, averaged acoustic evoked potential 100 msec after auditory stimulus) and EEG with an custom built, prototype electroencephalogram device from GE Healthcare and processed EEG (BIS-Index and Response- and State Entropy)
Mida/Remi: Active Comparator
sedation with midazolam and remifentanil
Device: Measurement of auditory ERPS (event related potentials) during sedation
Measurement of the amplitudes of auditory event related potentials (time locked, averaged acoustic evoked potential 100 msec after auditory stimulus) and EEG with an custom built, prototype electroencephalogram device from GE Healthcare and processed EEG (BIS-Index and Response- and State Entropy)

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 dexmedetomidine and midazolam (mida), each given in combination with remifentanil (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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age 18 years and older
  • healthy

Exclusion Criteria:

  • History of problems during anesthesia
  • Impairment of the auditory system
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00641563

Locations
Switzerland
Departement of Intensive Care Medicine - University Hospital Bern - Inselspital
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
GE Healthcare
  More Information

Publications:
Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):
Responsible Party: Department of Intensive Care Medicine, university Hospital Bern - Inselspital ( Matthias Haenggi )
Study ID Numbers: KIM-NMP3
Study First Received: February 25, 2008
Last Updated: March 21, 2008
ClinicalTrials.gov Identifier: NCT00641563     History of Changes
Health Authority: Switzerland: Ethikkommission

Keywords provided by University Hospital Inselspital, Berne:
dexmedetomidine
midazolam
remifentanil
Electroencephalography
Event related potentials
BIS
Bispectral Index
Response Entropy
State Entropy

Study placed in the following topic categories:
Anesthetics, Intravenous
Neurotransmitter Agents
Adrenergic alpha-Agonists
Remifentanil
Adrenergic Agents
Anesthetics
Central Nervous System Depressants
Healthy
Midazolam
Adrenergic Agonists
Anesthetics, General
Analgesics, Non-Narcotic
Hypnotics and Sedatives
Dexmedetomidine
Analgesics
Peripheral Nervous System Agents
Analgesics, Opioid

Additional relevant MeSH terms:
Anesthetics, Intravenous
Neurotransmitter Agents
Adrenergic alpha-Agonists
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Remifentanil
Physiological Effects of Drugs
Anesthetics
Central Nervous System Depressants
Adrenergic Agonists
Pharmacologic Actions
Anesthetics, General
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Hypnotics and Sedatives
Dexmedetomidine
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on September 10, 2009