Clinical trial NCT00641563
Conditions: Conscious Sedation Deep Sedation Critical Care
Keywords: dexmedetomidine midazolam remifentanil Electroencephalography Event related potentials BIS Bispectral Index Response Entropy State Entropy
Sponsor: Insel Gruppe AG, University Hospital Bern
Start date: 2004-03-01; Completion date: 2004-06-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Arms: arm 1: Sedation with dexmedetomidine and remifentanil followed by sedation with midazolam and remifentanil separated by one week arm 2: Sedation with midazolam and remifentanil followed by sedation with dexmedetomidine and remifentanil separated by one week
Interventions: intervention 1: Dexmedetomidine intervention 2: Midazolam intervention 3: Remifentanil
Intervention descriptions: intervention 1: Infusion of dexmedetomidine intervention 2: Midazolam infusion intervention 3: Infusion of remifentanil

Protocol documents: