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

Critical Illness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02903407
• Other study ID #: Pro00074866
• Status: Terminated
• Phase: Phase 4
• Start date: September 1, 2017
• Est. completion date: June 30, 2019

Study information

• Verified date: July 2020
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: June 30, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Critical Illness
• Deep Sedation
• Delirium
• Ventilators, Mechanical

Intervention

Drug:
• Midazolam
IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2.
• 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.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Searle NR, Côté 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	In Hospital Mortality	All-cause mortality during the hospitalization	One month or hospital discharge, whichever time point comes first
Secondary	Hospital Length of Stay	Index hospitalization length of stay in days	One month or hospital discharge, whichever time point comes first
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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