Providing "Good Sleep" for ICU Sedation

Summary

Cognitive dysfunction, either alone or as an element in the syndrome of delirium, is a common occurrence with an incidence as high as 75% in intensive care unit (ICU) patients and can independently result in serious consequences including higher mortality rate. Delirium develops through a complex interaction between the patient's baseline vulnerability (risk factors) and precipitating factors such as disruption of sleep that may occur during hospitalization. While sedative-hypnotic agents that are used to facilitate hypnosis and the management of mechanically ventilated patients converge on the neural substrate that mediate endogenous sleep, they do so at different juncture points depending on its molecular mechanism of hypnotic action. Hypnotic agents that modulate the GABAA receptor converge at the level of the hypothalamus while α2 adrenergic agonists converge on sleep pathways within the brainstem. This translational project seeks to determine whether sedation mediated by activation of α2 adrenoceptors (dexmedetomidine) is more like natural sleep than that provided by a sedative agent that modulates the GABAA receptor (propofol). The investigators will examine volunteers who will be monitored continuously by electroencephalography (EEG) and whole-brain functional connectivity by magnetoencephalography (MEG) during each of three sleep stages, namely, that induced by dexmedetomidine, propofol, or saline (natural sleep, control). The two drug-induced sleep regimens will be compared to natural sleep using EEG and brain connectivity by MEG

Conditions

• Sleep Disorders

Interventions

OTHER

Normal saline infusion

Normal saline infusion

DRUG

Dexmedetomidine

Infusion of Dexmedetomidine will be administrated during the overnight sleep study. An initial target concentration of 0.25 ng/ml will be selected. After 5 min, the sedative point will be assessed and the concentration will be adjusted stepwise by increments and decrements of 0.05 ng/ml. This process will be repeated until the target sedative state is achieved. Using the Richmond Agitation Sedation Scale (RASS) infusion rates, using known pharmacokinetic parameters will be adjusted to achieve equivalent levels of sedation (RASS -3) for both DEX and propofol sessions. We aim to achieve an RASS of -3 so that the subjects are "moderately sedated". This state of sedation will be maintained for 3-4 hours.

DRUG

Propofol

For propofol, an initial concentration of 0.75 ng/ml will be targeted. Depending on the score achieved, the infusion rate will be increased or decreased every 5 min by 0.2 ng/ml until the target sedative state is achieved. Note that the target sedative state (RASS score of -3) is the same for both DEX and propofol sessions, with the investigator being unaware of which drug is being administered. To ensure the investigator is not aware of the type of drug being administered, all drug delivery systems will be covered. Intravenous drug delivery will be continued throughout the scanning period for 3-4 hours to maintain equivalent levels of sedation for both DEX and propofol.

Sponsors & Collaborators

• Masimo Labs

  collaborator OTHER

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Mervyn Maze, MB, ChB · University of California, San Francisco

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-05-31

Primary Completion

2018-10-01

Completion

2018-11-01

Countries

• United States

Study Locations