Dexmedetomidine Use in ICU Sedation and Postoperative Recovery in Elderly Patients and Post-cardiac Surgery (DIRECT)

Increasing numbers of elderly patients are undergoing cardiac surgery. Elderly patients may have prolonged recovery following cardiac surgery when compared to other groups of patients, and are at higher risk of postoperative delirium, postoperative neurocognitive decline and reduced quality of life following hospital discharge.

The goals of sedation and analgesia for patients following cardiac surgery are multifold and include postoperative pain relief, the facilitation of ventilation, resolution of hypothermia and normalization of electrolyte balances. The choice of sedative agent however can impact postoperative outcomes. Dexmedetomidine has been associated with improved quality of recovery in patients undergoing major spine surgery and with a reduced incidence of delirium, both of which can impact a patient's quality of life following surgery. The investigators hypothesized that the use of dexmedetomidine as a sedative agent immediately following cardiac surgery in elderly patients would result in improved quality of recovery and a reduced incidence of delirium in the postoperative period, when compared to propofol. The investigators were also interested as to whether there was an associated improvement in neurocognitive outcomes in this population.

Questions:

• Does the use of dexmedetomidine as a sedative agent in ICU in elderly patients following cardiac surgery result in improved Quality of Recovery scores when compared with propofol?
• Does the use of dexmedetomidine as a sedative agent in ICU in elderly patients following CABG+/- AVR result in a reduced incidence of postoperative delirium as compared to propofol?
• Do these patients subsequently have a reduction in cognitive decline?

Study Overview

• Status: Unknown
• Conditions: Delirium; Cognitive Decline; Post-operative Quality of Recovery
• Intervention / Treatment: Drug: propofol; Drug: Dexmedetomidine

Detailed Description

Due to advances in surgical and anaesthetic techniques, increasing numbers of elderly patients are undergoing cardiac surgery. Elderly patients with multiple comorbidities undergoing cardiac surgery may have prolonged recovery following cardiac surgery when compared to other groups of patients, and are at higher risk of postoperative delirium, postoperative neurocognitive decline and reduced quality of life following hospital discharge.

Traditionally, outcomes following cardiac surgery were measured in terms of complication rates or mortality rates1. More recently however, quality of life (QoL) measures are increasingly being recognized as important outcome measurements following cardiac surgery2. Factors related to cardiac surgery and perioperative care which could potentially influence later QoL include quality of recovery following surgery, postoperative delirium, and postoperative neurocognitive decline.

Quality of recovery (QoR) is a newer concept, which aims to measure a patient's health status after surgery and anaesthesia. The use of dexmedetomidine during spinal surgery has been associated with improved quality of recovery in the early postoperative period3. There are suggestions that dexmedetomidine attenuates the increase in inflammatory mediators during a stress response4 which could have a role in the post-surgical stress response. There are no studies that have attempted to correlate dexmedetomidine use with quality of recovery following cardiac surgery.

The prevalence of delirium following cardiac surgery in patients over 60 years has been reported in the range 30-52% (5, 6). Delirium is a condition characterized by consciousness disturbances, concentration disorders, memory disturbances and hallucinations. There have been associations made between the choice of sedative and the prevalence of delirium in ICU patients. In a multicenter randomized trial predominantly involving medical patients in the ICU, those assigned to receive dexmedetomidine had a reduced risk of delirium and spent less time undergoing mechanical ventilation7. It is not known if the choice of sedation agent in this population impacts on the incidence of delirium following cardiac surgery. Delirium is associated with increased morbidity, prolonged hospital stay, increased mortality8

Cognitive decline refers to a condition in which intellectual abilities and memory seem impaired when the patient appears to have otherwise recovered from the surgery. It is a condition distinct from delirium or encephalopathy. Cognitive decline is common, and can be persist for months and years, following cardiac surgery. The reported incidence of cognitive decline after coronary artery bypass graft (CABG) has been reported as 53% at hospital discharge, 36% at 6 weeks and 42% at 5 years9. Elderly patient undergoing cardiac surgery are at increased risk for postoperative cognitive decline10. A strong relationship has been reported between cognitive decline and reduced quality of life following cardiac surgery11.

The goals of sedation and analgesia for patients following cardiac surgery are multifold and include postoperative pain relief, the facilitation of ventilation, resolution of hypothermia and normalization of electrolyte balances. The choice of sedative agent however can impact postoperative outcomes. Dexmedetomidine has been associated with improved quality of recovery in patients undergoing major spine surgery and with a reduced incidence of delirium, both of which can impact a patient's quality of life following surgery. We hypothesized that the use of dexmedetomidine as a sedative agent immediately following cardiac surgery in elderly patients would result in improved quality of recovery and a reduced incidence of delirium in the postoperative period, when compared to propofol. We were also interested as to whether there was an associated improvement in neurocognitive outcomes in this population.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Recruiting
      • Vancouver General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years to 105 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adults over 75yrs undergoing on-pump CABG +/- AVR

Exclusion Criteria:

• Consent refusal
• Language barrier
• Allergy to study drugs
• Receiving other alpha 2 agonists
• Dementia [mild cognitive impairment can be included]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol; Patients received propofol for post-operative sedation	Drug: propofol; propofol for post-sternal closure sedation
Active Comparator: Dexmedetomidine; Patients received dexmedetomidine for post-operative sedation	Drug: Dexmedetomidine; dexmedetomidine for post-sternal closure sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery - 40	Questionnaire	Post Operative Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Cognitive Acuity Screen	Questionnaire	Post Operative Day 5 and 6 months post operatively
Quality of Life Score SF-36	Questionnaire	6 months post operatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Secondary Outcomes - Number of Incidences of delirium	Number of Incidences of delirium	Up to 6 months post surgery date
Other Secondary Outcomes - Number of delirious days	Number of delirious days	Up to 6 months post surgery date
Other Secondary Outcomes - Time to extubation	Time to extubation	Up to 6 months post surgery date
Other secondary outcomes - Time to being discharge-ready from ICU	Time to being discharge-ready from ICU	Up to 6 months post surgery date
Other secondary outcome - Length of hospital stay	Length of hospital stay	Up to 6 months post surgery date
other secondary outcomes - Hospital mortality rate	Hospital mortality rate	Up to 6 months post surgery date
other secondary outcomes - Adverse events (hypotension, bradycardia, increased troponin, PONV)	Adverse events (hypotension, bradycardia, increased troponin, PONV)	Up to 6 months post surgery date

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: Principal Investigator: Janette Brohan, UBC

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: January 27, 2016
• First Submitted That Met QC Criteria: March 2, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; 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; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: H15-02301

Plan for Individual participant data (IPD)

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