Low-dose Dexmedetomidine and Postoperative Delirium After Cardiac Surgery

September 14, 2021 updated by: Dong-Xin Wang

Effect of Low-dose Dexmedetomidine on Postoperative Delirium in Patients After Cardiac Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial

Delirium is an acutely occurred and fluctuating cerebral dysfunction characterized with inattention, altered consciousness, cognitive decline and/or abnormal perception. It is common in the elderly after cardiac surgery and is associated with worse outcomes. Causes leading to delirium are multifactorial but sleep disturbances remains an important one. In previous studies, sedative-dose dexmedetomidine improves sleep quality in ICU patients with mechanical ventilation; and low-dose dexmedetomidine improves sleep quality in postoperative patients without mechanical ventilation. In recent studies of elderly after noncardiac surgery, night-time infusion of low-dose dexmedetomidine reduces delirium and improves 2-year survival. The investigators hypothesize that, for elderly patients after cardiac surgery, night-time infusion of dexmedetomidine may also improve sleep quality, reduce delirium development and improve 2-year survival.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Delirium is an acutely occurred and fluctuating cerebral dysfunction characterized with inattention, altered consciousness, cognitive decline and/or abnormal perception. It is common in the elderly after cardiac surgery and is associated with worse outcomes.

The development of delirium is a consequence of multiple factors. For patients undergoing cardiac surgery, surgical stress and/or cardiopulmonary bypass can produce hyper-inflammatory and stress response, both of which are important factors leading to delirium. Meanwhile, patients in ICU after major surgery often develop sleep disturbances, which are also associated with increased risk of delirium.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anxiolytic properties. In previous studies of elderly patients admitted to ICU after non-cardiac surgery, continuous infusion of low-dose dexmedetomidine during nighttime improves sleep quality, reduces delirium, and improves 2-year survival.

The investigators hypothesize that, for patients admitted to ICU after cardiac surgery, nighttime infusion of low-dose dexmedetomidine can decrease the incidence of delirium and improve long-term survival. The purpose of this study is to investigate the effect of nighttime infusion of low-dose dexmedetomidine on postoperative sleep quality, delirium, and 2-year survival in elderly patients admitted to ICU after cardiac surgery.

Study Type

Interventional

Enrollment (Anticipated)

502

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100034
        • Beijing University First Hospital
      • Beijing, Beijing, China, 100037
        • Fuwai Hospital of Chinese Academy of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥60 years but <90 years;
  2. Scheduled to undergo cardiac surgery with cardiopulmonary bypass under general anesthesia;
  3. Expected to stay in the intensive care unit (ICU) for at least 1 night after surgery.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded.

  1. Refuse to participate in the study;
  2. Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
  3. Preoperative obstructive sleep apnea (previously diagnosed as obstructive sleep apnea, or the snoring, tiredness, observed apnea, high blood pressure-body mass index, age, neck circumference and gender [STOP-Bang] questionnaires ≥3);
  4. Inability to communicate during the preoperative period because of coma, profound dementia or language barrier;
  5. Preoperative sick sinus syndrome, severe sinus bradycardia (< 50 beats per minute), or second-degree atrioventricular block or above without pacemaker;
  6. Severe hepatic dysfunction (Child-Pugh class C);
  7. Severe renal dysfunction (requirement of renal replacement therapy) before surgery;
  8. Presence of delirium (diagnosed by the Confusion Assessment Method [CAM]/CAM for the Intensive Care Unit [CAM-ICU]);
  9. Current treatment with dexmedetomidine or clonidine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine group
Dexmedetomidine infusion is administered from 16:00 to 08:00 during the night of surgery; and will repeated for a maximum of 5 consecutive nights. For patients with mechanical ventilation, the infusion rate is 0.2-0.7 ug/kg/h; for those without mechanical ventilation, the infusion rate is 0.05-0.2 ug/kg/h. The target depth of sedation is Richmond Agitation-Sedation Scale (RASS) -1.
Drug: Dexmedetomidine
Dexmedetomidine infusion is administered from 16:00 to 08:00 during the night of surgery in the intensive care unit; and will repeated for a maximum of 5 consecutive nights. For patients with mechanical ventilation, the infusion rate is 0.2-0.7 ug/kg/h; for those without mechanical ventilation, the infusion rate is 0.05-0.2 ug/kg/h. The target depth of sedation is Richmond Agitation-Sedation Scale (RASS) -1.
Other Names:
  • Low-dose dexmedetomidine infusion
PLACEBO_COMPARATOR: Placebo group
Placebo (normal saline) infusion is administered from 16:00 to 08:00 in the same speed for the same duration as in the dexmedetomidine group. The conventional sedation is provided when necessary with propofol and/or midazolam by intravenous infusion/injection. The target depth of sedation depth is RASS -1.
Drug: Placebo
Placebo (normal saline) infusion is administered in the same rate for the same duration as in the dexmedetomidine group. The conventional sedation is provided when necessary with propofol and/or midazolam by intravenous infusion/injection. The target depth of sedation depth is RASS -1.
Other Names:
  • Normal saline infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of delirium within the first 5 days after surgery
Time Frame: During the first 5 days after surgery
Delirium is assessed twice daily (8:00-10:00 am, 18:00-20:00 pm) with the Confusion Assessment Method (CAM, for patients without mechanical ventilation) or CAM for the intensive care unit (CAM-ICU, for patients with mechanical ventilation) during postoperative days 1-5.
During the first 5 days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay in hospital after surgery
Time Frame: Up to 30 days after surgery
Length of stay in hospital after surgery
Up to 30 days after surgery
Duration of mechanical ventilation after surgery
Time Frame: Up to 30 days after surgery
Duration of mechanical ventilation after surgery
Up to 30 days after surgery
Length of stay in ICU after surgery
Time Frame: Up to 30 days after surgery
Length of stay in ICU after surgery
Up to 30 days after surgery
Incidence of Major Adverse Cardiovascular Events (MACEs) within 30 days after surgery
Time Frame: Up to 30 days after surgery
Postoperative Major Adverse Cardiac Events (MACEs) include in-hospital death, myocardial infarction, second surgery, non-fetal cardiac arrest/ventricular fibrillation, and stroke. The occurrence of major postoperative events is followed up twice daily during postoperative days 1-5, then once a week until 30 days after surgery.
Up to 30 days after surgery
Incidence of other complications
Time Frame: Up to 30 days after surgery
Incidence of other complications (including hospital re-admission) within 30 days after surgery.
Up to 30 days after surgery
All-cause 30-day mortality
Time Frame: At 30 days after surgery
All-cause mortality within 30 days after surgery
At 30 days after surgery
Subjective sleep quality at 30 days after surgery
Time Frame: At 30 days after surgery
Subjective sleep quality at 30 days after surgery is assessed with Pittsburgh sleep quality index (PSQI)
At 30 days after surgery
2 -year Major Adverse Cardiac and Cerebrovascular Events (MACCEs)-free survival after surgery
Time Frame: Up to 2 years after surgery
Major Adverse Cardiac and Cerebrovascular Events (MACCEs) include cardiac death, myocardial infarction, revascularization, and stroke.
Up to 2 years after surgery
2-year overall survival after surgery
Time Frame: Up to 2 years after surgery
2-year survival overall after surgery
Up to 2 years after surgery
Cognitive function in 1- and 2-year survivors
Time Frame: At the end of the 1st and 2nd years after surgery
Cognitive function in 1- and 2-year survivors is assessed with the modified Telephone Interview for Cognitive Status (TICS-m, score ranges from 0 to 40, with higher score indicating better function).
At the end of the 1st and 2nd years after surgery
Quality of life in 1- and 2- year survivors
Time Frame: At the end of the 1st and 2nd years after surgery
Quality of life in 1- and 2-year survivors is assessed with the 36-Item Short Form Health Survey (SF-36). The SF-36 evaluates 8 different domains of quality of life, i.e., physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The score of each domain ranges from 0 to 100, with high score indicating better function.
At the end of the 1st and 2nd years after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alterations of sleep architecture
Time Frame: During the night of surgery
Sleep architecture is monitored with polysomnograph from 21:00 pm in the night of surgery to 06:00 am on the first day after surgery in part of enrolled patients (selected according to randomization block).
During the night of surgery
The Numeric Rating Scale (NRS) pain score within 5 days after surgery.
Time Frame: At 2, 6, 24, 48, 72, 96, and 120 hours (i.e., the 5th day) after surgery.
The Numeric Rating Scale (NRS) pain score is assessed with the NRS (an 11-point scale where 0=no pain and 10=the worst pain).
At 2, 6, 24, 48, 72, 96, and 120 hours (i.e., the 5th day) after surgery.
Subjective sleep quality within 5 days after surgery
Time Frame: During the first 5 days after surgery
Subjective sleep quality is assessed with NRS (an 11-point scale where 0=the best sleep and 10=the worst sleep) once daily (8:00-10:00 am) during postoperative days 1-5.
During the first 5 days after surgery
Daily prevalence of delirium during postoperative days 1-5
Time Frame: During the first 5 days after surgery
Daily prevalence of delirium during postoperative days 1-5
During the first 5 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dong-Xin Wang

Collaborators

Fu Wai Hospital, Beijing, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 16, 2019

Primary Completion (ACTUAL)

July 3, 2021

Study Completion (ANTICIPATED)

August 1, 2023

Study Registration Dates

First Submitted

August 5, 2018

First Submitted That Met QC Criteria

August 8, 2018

First Posted (ACTUAL)

August 10, 2018

Study Record Updates

Last Update Posted (ACTUAL)

September 16, 2021

Last Update Submitted That Met QC Criteria

September 14, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-181

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Delirium

Clinical Trials on Dexmedetomidine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe