Low-dose Dexmedetomidine and Postoperative Delirium After Cardiac Surgery

Not Applicable

Active, not recruiting

• Conditions: Cardiac Surgery; Cardiopulmonary Bypass; Dexmedetomidine; Survival; Delirium
• Interventions: Drug: Placebo; Drug: Dexmedetomidine

• Registration Number: NCT03624595
• Lead Sponsor: Dong-Xin Wang

Brief 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.

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 Timeline

• Study First Submitted: 2018-08-05
• Study First Submitted QC: 2018-08-08
• Study First Posted: 2018-08-10
• Study Start: 2019-04-16
• Primary Completion: 2021-07-03
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-11
• Last Update Posted: 2024-05-14
• Study Completion: 2024-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 502

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	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.
Dexmedetomidine group	Dexmedetomidine	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.

Primary Outcome Measures

Name	Time	Method
Incidence of delirium within the first 5 days after surgery	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.

Secondary Outcome Measures

Name	Time	Method
All-cause 30-day mortality	At 30 days after surgery	All-cause mortality within 30 days after surgery
Duration of mechanical ventilation after surgery	Up to 30 days after surgery	Duration of mechanical ventilation after surgery
Length of stay in hospital after surgery	Up to 30 days after surgery	Length of stay in hospital after surgery
Subjective sleep quality at 30 days after surgery	At 30 days after surgery	Subjective sleep quality at 30 days after surgery is assessed with Pittsburgh sleep quality index (PSQI)
Length of stay in ICU after surgery	Up to 30 days after surgery	Length of stay in ICU after surgery
Incidence of Major Adverse Cardiovascular Events (MACEs) within 30 days after surgery	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.
Incidence of other complications	Up to 30 days after surgery	Incidence of other complications (including hospital re-admission) within 30 days after surgery.
2 -year Major Adverse Cardiac and Cerebrovascular Events (MACCEs)-free survival after surgery	Up to 2 years after surgery	Major Adverse Cardiac and Cerebrovascular Events (MACCEs) include cardiac death, myocardial infarction, revascularization, and stroke.
Cognitive function in 1- and 2-year survivors	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).
2-year overall survival after surgery	Up to 2 years after surgery	2-year survival overall after surgery
Quality of life in 1- and 2- year survivors	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.

Trial Locations

Locations (2)

Fuwai Hospital of Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Beijing University First Hospital; 🇨🇳 Beijing, Beijing, China