Providing "Good Sleep" for ICU Sedation

NCT01342328 | Completed DMC

• 1 other identifier: 10-03906
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Sleep disruption; Sleep hygiene; Sedative agents and sleep; Electroencephalography; REM sleep; Magnetoencephalography

Outcome Measures

Primary Outcomes (2)

• Compare the electroencephalography features of sleep produced by three sleep-induced regimens

  The investigators will evaluate the "power" in the delta rhythm range and amount of slow-wave-sleep

  Data will be collected during patient's sleep, which will last 4hours.

• Compare the magnetoencephalography features of sleep produced by three sleep induced regimens

  The investigators will evaluate the magnetoencephalography-defined brain connectivity

  Data will be collected during patient's sleep, which will last 4hours.

Study Arms (3)

Control

PLACEBO COMPARATOR

For this arm, the volunteer subject will receive a saline infusion during the sleep session.

Other: Normal saline infusion

Dexmedetomidine (DEX)

EXPERIMENTAL

For this arm, the volunteer subject will receive a DEX infusion for sedation during the sleep session.

Drug: Dexmedetomidine

Propofol

EXPERIMENTAL

For this arm, the volunteer subject will receive a propofol infusion for sedation during the sleep session.

Drug: Propofol

Interventions

Normal saline infusion OTHER

Normal saline infusion

Control

Dexmedetomidine DRUG

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.

Also known as: Precedex, DEX

Dexmedetomidine (DEX)

Propofol DRUG

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.

Also known as: Diprivan

Propofol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteer agreement and written informed consent
• Healthy female or male between 18 and 45 years of age
• Body Mass Index \< 30 kg/m2
• Non-pregnant and non-lactating
• Normal airway anatomy (Mallampati class I)

You may not qualify if:

• Subject has a history of recent alcohol or drug abuse
• Subject is unable to communicate in English
• Subject is unwilling to meet fast guidelines (fast light meal or non-human milk for at least 8 hours, and clear liquids at least for 2 hours prior to induction of sedation on the day of the study)
• Subject has taken caffeine containing beverages less than 8 hours before study begins
• Subject is not able to avoid sleep for a minimum of 16 hours prior to testing
• Subject has a known allergy to either of the sedative-hypnotic drugs to be used in the study
• Subject has abnormal airway anatomy, including loose teeth
• Subject has any family history of complications from anesthesia
• Subject has history of sleep apnea
• Subject has any reported illness, upper respiratory tract infection, abnormal vital signs, or concerning findings on the physical exam for the past 6 weeks
• Subject has a positive urine pregnancy test
• Subject is unable to sleep supine.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Masimo Labs: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Sleep Wake Disorders; Sleep Hygiene

Interventions

Dexmedetomidine; Propofol

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Mervyn Maze, MB, ChB

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 7, 2010
• First Posted: April 27, 2011
• Study Start: May 1, 2012
• Primary Completion: October 1, 2018
• Study Completion: November 1, 2018
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

US (1)