Pain, Agitation and Delirium (PAD) Protocol in the Duke CICU

Sponsor
Duke University (Other)
Overall Status
Terminated
CT.gov ID
NCT02903407
Collaborator
(none)
7
1
2
21.9
0.3

Study Details

Study Description

Brief Summary

This study aims to examine the use of protocol directed sedation using the Duke PAD protocol with the current sedation medications of propofol or dexmedetomidine compared to the PAD protocol with midazolam, per cardiac intensive care unit (CICU) usual care, as an initial step toward understanding the best management of sedation in these patients.

Detailed Description

The optimal approach to management of sedation in the Intensive Care Unit (ICU) has become a topic of increasing interest. The most recent guidelines outline the pharmacologic mechanisms of commonly used medications as well as scales on which to measure goals of pain, sedation, agitation and delirium in the critically ill patient. This guideline is based on a cadre of randomized controlled trials examining the medications in the medical intensive care unit and post cardiac surgery patient. Notably, in each of the trials, patients presenting with acute myocardial infarction, heart failure or cardiogenic shock have been excluded or largely underrepresented.

Using the current guidelines as a foundation, a new pain, agitation and delirium (PAD) protocol, which prioritizes the use of propofol or dexmedetomidine for sedation, was developed and instituted at Duke University Hospital. However, use of this protocol in the CICU has raised important considerations. Some of these stem from the specific hemodynamic characteristics of the population, including significant bradycardia and hypotension, which can be worsened due to known side effects of propofol and dexmedetomidine. It remains unclear whether the benefits of these medications outweigh the risks in CICU patients as the use of these medications has not been studied previously in this population. This study aims to examine the use of protocol directed sedation using the Duke PAD protocol with the current sedation medications of propofol or dexmedetomidine compared to the PAD protocol with midazolam, per CICU usual care, as an initial step toward understanding the best management of sedation in these patients.

Project Aims Include:
  1. Examine the efficacy of the PAD protocol using propofol or dexmedetomidine versus midazolam with regard to goal sedation, pain control and level of delirium in intubated Duke CICU patients.

  2. Determine differences in duration of ventilator days, CICU stay and total hospital stay with the PAD protocol using propofol or dexmedetomidine compared to midazolam in the Duke CICU.

  3. Compare the rates of adverse effects of the current PAD protocol with propofol or dexmedetomidine versus midazolam for sedation in the Duke CICU, including hypotension, bradycardia, difficulty with ventilator weaning due to sedation, and delirium.

Study Design

Study Type:
Interventional
Actual Enrollment :
7 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Pain, Agitation and Delirium Protocol in Ventilated Patients in the Duke CICU
Actual Study Start Date :
Sep 1, 2017
Actual Primary Completion Date :
Jun 30, 2019
Actual Study Completion Date :
Jun 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Midazolam

IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline.

Drug: Midazolam
IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
Other Names:
  • Versed
  • Active Comparator: Propofol or Dexmedetomidine

    Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline.

    Drug: Propofol
    IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Other Names:
  • Diprivan
  • Drug: Dexmedetomidine
    IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Other Names:
  • Precedex
  • Outcome Measures

    Primary Outcome Measures

    1. Intensive Care Unit Length of Stay [One month or hospital discharge, whichever time point comes first]

      Number of days of admission to the CICU during the index hospitalization

    Secondary Outcome Measures

    1. In Hospital Mortality [One month or hospital discharge, whichever time point comes first]

      All-cause mortality during the hospitalization

    2. Hospital Length of Stay [One month or hospital discharge, whichever time point comes first]

      Index hospitalization length of stay in days

    3. Number of Participants With Increased Vasopressor Requirement [One month or hospital discharge, whichever time point comes first]

      Patients will be monitored for increased pressor requirement during the CICU stay

    4. Number of Participants With Bradycardia [One month or hospital discharge, whichever time point comes first]

      Patients will be monitored for bradycardia which may be associated with sedation drug. Average heart rate before, during and after use of drug will be recorded for each patient.

    5. Number of Ventilator Days [One month or hospital discharge, whichever time point comes first]

      Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization

    6. Number of Days From Decision to Extubate to True Extubation [One month or hospital discharge, whichever time point comes first]

      The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated

    7. Number of Days Alive During Admission and Free From Delirium or Coma [One month or hospital discharge, whichever time point comes first]

      The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented

    8. Percentage of Time at Goal Sedation [One month or hospital discharge, whichever time point comes first]

      Will use RASS (Richmond Agitation and Sedation Scale) to assess level of sedation as per standard of care by nurses in the CICU. Data that is recorded will be evaluated following discharge. The RASS ranges from -5 (unrousable) to +4 (combative) and 0 (zero) = alert and calm and goal sedation is considered a RASS level of 0 to -2.

    9. Time From Withdrawal of Sedation to ICU Discharge [One month or hospital discharge, whichever time point comes first]

      The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU

    10. Number of Participants With Delirium [One month or hospital discharge, whichever time point comes first]

      Will use the Confusion Assessment Method for the ICU (CAM-ICU) to assess presence of delirium as per standard of care by nurses in the CICU. Patients with CAM-ICU data recorded will be included.

    11. Pain Management [One month or hospital discharge, whichever time point comes first]

      Will use the CPOT (Critical-Care Pain Observation Tool) score to assess pain level as per standard of care by nurses in the CICU. The CPOT has a range of 0 to 8. A CPOT score of ≤ 2 = minimal to no pain present and >2 = unacceptable level of pain. Data that is recorded will be evaluated following discharge.

    12. Number of Participants Requiring Reintubation [One month or hospital discharge, whichever time point comes first]

      Following ICU discharge, patient charts will be reviewed to evaluate whether they required reintubation. If so, will determine whether necessity of reintubation was related to delirium.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • All patients admitted to the Duke CICU, who require intubation and sedation for mechanical ventilation that is expected to be >24 hours in duration will be included, unless they meet the specified exclusion criteria.

    • Patients intubated within one hour prior to care transition to the CICU will also be screened for inclusion.

    Exclusion Criteria:
    • Exclusion criteria include patients following resuscitation from cardiac arrest who are treated on the cooling protocol

    • patients who have suffered a neurologic event (seizure, stroke) or who have baseline dementia, both of which could limit delirium assessment

    • patients with child class B and C liver disease

    • patients with known allergy to study medications.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Duke University Medical Center Durham North Carolina United States 27710

    Sponsors and Collaborators

    • Duke University

    Investigators

    • Principal Investigator: Kristin Newby, MD, Duke University

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Duke University
    ClinicalTrials.gov Identifier:
    NCT02903407
    Other Study ID Numbers:
    • Pro00074866
    First Posted:
    Sep 16, 2016
    Last Update Posted:
    Jul 13, 2020
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Duke University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Patients were recruited from the Duke CICU between September 1, 2017 and June 30, 2019. Patients were identified by the rounding team for potential inclusion in the sedation trial and then screened by study team members to determine whether they met inclusion criteria. Consent was obtained from eligible patient's primary decision maker.
    Pre-assignment Detail No enrolled participants were excluded from the study prior to group assignment.
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Period Title: Overall Study
    STARTED 4 3
    COMPLETED 4 3
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Midazolam Propofol or Dexmedetomidine Total
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Total of all reporting groups
    Overall Participants 4 3 7
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    72.5
    57.0
    70.0
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    3
    100%
    5
    71.4%
    Male
    2
    50%
    0
    0%
    2
    28.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    25%
    1
    33.3%
    2
    28.6%
    White
    3
    75%
    2
    66.7%
    5
    71.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    3
    100%
    7
    100%
    BMI (kg/m^2) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [kg/m^2]
    36.1
    34.4
    34.4
    Ejection Fraction (Percentage of blood) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Percentage of blood]
    30.0
    55.0
    40.0

    Outcome Measures

    1. Primary Outcome
    Title Intensive Care Unit Length of Stay
    Description Number of days of admission to the CICU during the index hospitalization
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [Days]
    4.1
    10.0
    2. Secondary Outcome
    Title In Hospital Mortality
    Description All-cause mortality during the hospitalization
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Number [participants]
    1
    25%
    1
    33.3%
    3. Secondary Outcome
    Title Hospital Length of Stay
    Description Index hospitalization length of stay in days
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [Days]
    19.5
    30.0
    4. Secondary Outcome
    Title Number of Participants With Increased Vasopressor Requirement
    Description Patients will be monitored for increased pressor requirement during the CICU stay
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Count of Participants [Participants]
    2
    50%
    2
    66.7%
    5. Secondary Outcome
    Title Number of Participants With Bradycardia
    Description Patients will be monitored for bradycardia which may be associated with sedation drug. Average heart rate before, during and after use of drug will be recorded for each patient.
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Count of Participants [Participants]
    0
    0%
    0
    0%
    6. Secondary Outcome
    Title Number of Ventilator Days
    Description Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [Days]
    2.5
    6.8
    7. Secondary Outcome
    Title Number of Days From Decision to Extubate to True Extubation
    Description The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [Days]
    0
    0
    8. Secondary Outcome
    Title Number of Days Alive During Admission and Free From Delirium or Coma
    Description The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    CAM-ICU was only documented in 3/7 of the patients enrolled, all of whom were in the midazolam arm of the study. Only these patients were included in this analysis.
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 3 0
    Median (Inter-Quartile Range) [Days]
    14.0
    9. Secondary Outcome
    Title Percentage of Time at Goal Sedation
    Description Will use RASS (Richmond Agitation and Sedation Scale) to assess level of sedation as per standard of care by nurses in the CICU. Data that is recorded will be evaluated following discharge. The RASS ranges from -5 (unrousable) to +4 (combative) and 0 (zero) = alert and calm and goal sedation is considered a RASS level of 0 to -2.
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [percentage of time]
    63.3
    63.2
    10. Secondary Outcome
    Title Time From Withdrawal of Sedation to ICU Discharge
    Description The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [Days]
    1.6
    5.6
    11. Secondary Outcome
    Title Number of Participants With Delirium
    Description Will use the Confusion Assessment Method for the ICU (CAM-ICU) to assess presence of delirium as per standard of care by nurses in the CICU. Patients with CAM-ICU data recorded will be included.
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    Patients with CAM-ICU score documented in the CICU (3/7 participants, all in the midazolam arm of the study)
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 3 0
    Count of Participants [Participants]
    1
    25%
    12. Secondary Outcome
    Title Pain Management
    Description Will use the CPOT (Critical-Care Pain Observation Tool) score to assess pain level as per standard of care by nurses in the CICU. The CPOT has a range of 0 to 8. A CPOT score of ≤ 2 = minimal to no pain present and >2 = unacceptable level of pain. Data that is recorded will be evaluated following discharge.
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Median (Inter-Quartile Range) [score on a scale]
    0.0
    0.0
    13. Secondary Outcome
    Title Number of Participants Requiring Reintubation
    Description Following ICU discharge, patient charts will be reviewed to evaluate whether they required reintubation. If so, will determine whether necessity of reintubation was related to delirium.
    Time Frame One month or hospital discharge, whichever time point comes first

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    Measure Participants 4 3
    Count of Participants [Participants]
    0
    0%
    1
    33.3%

    Adverse Events

    Time Frame From time of enrollment to hospital discharge - a range of 2-29 days for the patients enrolled in the trial
    Adverse Event Reporting Description
    Arm/Group Title Midazolam Propofol or Dexmedetomidine
    Arm/Group Description IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
    All Cause Mortality
    Midazolam Propofol or Dexmedetomidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/4 (25%) 1/3 (33.3%)
    Serious Adverse Events
    Midazolam Propofol or Dexmedetomidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Midazolam Propofol or Dexmedetomidine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%)

    Limitations/Caveats

    Our trial was terminated prior to goal enrollment due to difficulty with enrollment in this critically ill population of patients. The data here represent a small sample size of patients and should be viewed as pilot data for hypothesis generation.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Angela Lowenstern
    Organization Duke University
    Phone 919-684-0111
    Email angela.sandelin@duke.edu
    Responsible Party:
    Duke University
    ClinicalTrials.gov Identifier:
    NCT02903407
    Other Study ID Numbers:
    • Pro00074866
    First Posted:
    Sep 16, 2016
    Last Update Posted:
    Jul 13, 2020
    Last Verified:
    Jul 1, 2020