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

Pain, Agitation and Delirium Protocol in Ventilated Patients in the Duke CICU

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.

Study Overview

• Status: Terminated
• Conditions: Critical Illness; Deep Sedation; Ventilators, Mechanical
• Intervention / Treatment: Drug: Midazolam; Drug: Propofol; Drug: Dexmedetomidine

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In Hospital Mortality	All-cause mortality during the hospitalization	One month or hospital discharge, whichever time point comes first
Hospital Length of Stay	Index hospitalization length of stay in days	One month or hospital discharge, whichever time point comes first
Number of Participants With Increased Vasopressor Requirement	Patients will be monitored for increased pressor requirement during the CICU stay	One month or hospital discharge, whichever time point comes first
Number of Participants With Bradycardia	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.	One month or hospital discharge, whichever time point comes first
Number of Ventilator Days	Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization	One month or hospital discharge, whichever time point comes first
Number of Days From Decision to Extubate to True Extubation	The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated	One month or hospital discharge, whichever time point comes first
Number of Days Alive During Admission and Free From Delirium or Coma	The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented	One month or hospital discharge, whichever time point comes first
Percentage of Time at Goal Sedation	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.	One month or hospital discharge, whichever time point comes first
Time From Withdrawal of Sedation to ICU Discharge	The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU	One month or hospital discharge, whichever time point comes first
Number of Participants With Delirium	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.	One month or hospital discharge, whichever time point comes first
Pain Management	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.	One month or hospital discharge, whichever time point comes first
Number of Participants Requiring Reintubation	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.	One month or hospital discharge, whichever time point comes first

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Kristin Newby, MD, Duke University

Publications and helpful links

General Publications

• Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
• Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.
• Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16. Erratum In: Crit Care. 2011;15(1):402.
• Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.
• Carson SS, Kress JP, Rodgers JE, Vinayak A, Campbell-Bright S, Levitt J, Bourdet S, Ivanova A, Henderson AG, Pohlman A, Chang L, Rich PB, Hall J. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med. 2006 May;34(5):1326-32. doi: 10.1097/01.CCM.0000215513.63207.7F.
• Hall RI, Sandham D, Cardinal P, Tweeddale M, Moher D, Wang X, Anis AH; Study Investigators. Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial. Chest. 2001 Apr;119(4):1151-9. doi: 10.1378/chest.119.4.1151.
• Huey-Ling L, Chun-Che S, Jen-Jen T, Shau-Ting L, Hsing-I C. Comparison of the effect of protocol-directed sedation with propofol vs. midazolam by nurses in intensive care: efficacy, haemodynamic stability and patient satisfaction. J Clin Nurs. 2008 Jun;17(11):1510-7. doi: 10.1111/j.1365-2702.2007.02128.x.
• Searle NR, Cote S, Taillefer J, Carrier M, Gagnon L, Roy M, Lussier D. Propofol or midazolam for sedation and early extubation following cardiac surgery. Can J Anaesth. 1997 Jun;44(6):629-35. doi: 10.1007/BF03015447.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimate): September 16, 2016

Study Record Updates

• Last Update Posted (Actual): July 13, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Intensive Care Units; Deep Sedation; Ventilators, Mechanical
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Delirium; Critical Illness; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Propofol; Dexmedetomidine
• Other Study ID Numbers: Pro00074866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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