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

Phase 4

Terminated

• Conditions: Deep Sedation; Ventilators, Mechanical; Critical Illness
• Interventions: Drug: Midazolam; Drug: Propofol; Drug: Dexmedetomidine

• Registration Number: NCT02903407
• Lead Sponsor: Duke University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-09-02
• Study First Submitted QC: 2016-09-12
• Study First Posted: 2016-09-16
• Study Start: 2017-09-01
• Primary Completion: 2019-06-30
• Study Completion: 2019-06-30
• Results First Submitted: 2020-06-19
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-10
• Last Update Submitted: 2020-07-10
• Results First Posted: 2020-07-13
• Last Update Posted: 2020-07-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midazolam	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.
Propofol or Dexmedetomidine	Propofol	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 or Dexmedetomidine	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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.
Hospital Length of Stay	One month or hospital discharge, whichever time point comes first	Index hospitalization length of stay in days
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
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
In Hospital Mortality	One month or hospital discharge, whichever time point comes first	All-cause mortality during the hospitalization
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.
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.
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
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.
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
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.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States