Low-dose Dexmedetomidine and Postoperative Delirium After Cardiac Surgery

Delirium Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03624595
• Other study ID #: 2018-181
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 16, 2019
• Est. completion date: August 2023

Study information

• Verified date: September 2021
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 502
• Est. completion date: August 2023
• Est. primary completion date: July 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Surgery
• Cardiopulmonary Bypass
• Delirium
• Dexmedetomidine
• Survival

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing University First Hospital	Beijing	Beijing
China	Fuwai Hospital of Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Dong-Xin Wang	Fu Wai Hospital, Beijing, China

Country where clinical trial is conducted

China, 

References & Publications (35)

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Alterations of sleep architecture	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
Other	The Numeric Rating Scale (NRS) pain score within 5 days 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.
Other	Subjective sleep quality within 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
Other	Daily prevalence of delirium during postoperative days 1-5	Daily prevalence of delirium during postoperative days 1-5	During the first 5 days after surgery
Primary	Incidence of delirium within 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	Duration of mechanical ventilation after surgery	Duration of mechanical ventilation after surgery	Up to 30 days after surgery
Secondary	Length of stay in ICU after surgery	Length of stay in ICU after surgery	Up to 30 days after surgery
Secondary	Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Secondary	Incidence of Major Adverse Cardiovascular Events (MACEs) within 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
Secondary	Incidence of other complications	Incidence of other complications (including hospital re-admission) within 30 days after surgery.	Up to 30 days after surgery
Secondary	All-cause 30-day mortality	All-cause mortality within 30 days after surgery	At 30 days after surgery
Secondary	Subjective sleep quality 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
Secondary	2 -year Major Adverse Cardiac and Cerebrovascular Events (MACCEs)-free survival after surgery	Major Adverse Cardiac and Cerebrovascular Events (MACCEs) include cardiac death, myocardial infarction, revascularization, and stroke.	Up to 2 years after surgery
Secondary	2-year overall survival after surgery	2-year survival overall after surgery	Up to 2 years after surgery
Secondary	Cognitive function in 1- and 2-year survivors	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
Secondary	Quality of life in 1- and 2- year survivors	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