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

NCT ID: NCT00641563

Last Updated: 2011-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2004-06-30

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

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.

Conditions

Conscious Sedation; Deep Sedation; Critical Care

Keywords

dexmedetomidine; midazolam; remifentanil; Electroencephalography; Event related potentials; BIS; Bispectral Index; Response Entropy; State Entropy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Dex/Remi followed by Mida/Remi

Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Infusion of dexmedetomidine

Midazolam

Intervention Type: DRUG

Midazolam infusion

Remifentanil

Intervention Type: DRUG

Infusion of remifentanil

Mida/Remi followed by Dexa/Remi

Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

Infusion of dexmedetomidine

Midazolam

Intervention Type: DRUG

Midazolam infusion

Remifentanil

Intervention Type: DRUG

Infusion of remifentanil

Interventions

Dexmedetomidine

Infusion of dexmedetomidine

Intervention Type: DRUG

Midazolam

Midazolam infusion

Intervention Type: DRUG

Remifentanil

Infusion of remifentanil

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• age 18 years and older
• healthy

Exclusion Criteria

• History of problems during anesthesia
• Impairment of the auditory system

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GE Healthcare

INDUSTRY

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Department of Intensive Care Medicine, university Hospital Bern - Inselspital

Principal Investigators

Matthias Haenggi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bern

Locations

Departement of Intensive Care Medicine - University Hospital Bern - Inselspital

Bern, , Switzerland

Countries

Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 15562062 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17056949 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19228415 (View on PubMed)

Other Identifiers

KIM-NMP3

Identifier Type: -

Identifier Source: org_study_id