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
  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
Drug: Dexmedetomidine
Drug: Midazolam
Drug: Remifentanil

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
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 (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)


Secondary Outcome Measures:
  • 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.)


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
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

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.

  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
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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
Investigators
Principal Investigator: Matthias Haenggi, MD University of Bern
  More Information

Publications:
Responsible Party: Matthias Haenggi, Department of Intensive Care Medicine, university Hospital Bern - Inselspital
ClinicalTrials.gov Identifier: NCT00641563     History of Changes
Other Study ID Numbers: KIM-NMP3
Study First Received: February 25, 2008
Results First Received: April 27, 2009
Last Updated: October 13, 2011
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

Additional relevant MeSH terms:
Midazolam
Dexmedetomidine
Remifentanil
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on July 23, 2014