Effects of Two Different Sedation Regimes on Auditory Evoked Potentials and Electroencephalogram (EEG)
Condition: Conscious Sedation; Deep Sedation; Critical Care
Study type: Interventional

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.
    

Intervention name(s): Dexmedetomidine; Midazolam; Remifentanil
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Infusion of dexmedetomidine; Midazolam infusion; Infusion of remifentanil
Intervention MeSH terms: Midazolam; Dexmedetomidine; Remifentanil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: dexmedetomidine; midazolam; remifentanil; Electroencephalography; Event related potentials; BIS; Bispectral Index; Response Entropy; State Entropy