Effect of Preoperative Sleep Intervention on Postoperative Delirium in Adult Patients Undergoing Cardiac Surgery

Effect of Preoperative Sleep Intervention on Postoperative Delirium in Adult Patients Undergoing Cardiac Surgery: a Multicenter Randomized Controlled Trial

This is a multicenter, randomized, controlled clinical trial aimed to determine whether preoperative sleep interventions could reduce the incidence of adverse outcomes, such as postoperative delirium, in adult patients undergoing cardiac surgery. The study will include adult patients undergoing coronary artery bypass grafting and/or valve surgery with concomitant sleep disorders, as assessed by the Pittsburgh Sleep Quality Index. All participants will be randomly assigned to placebo, placebo + cognitive behavioral therapy, and melatonin + cognitive behavioral therapy in a 1:1:1 ratio. The primary outcome is the incidence of postoperative delirium within 7 days after surgery or before discharge, and secondary outcomes include postoperative cognitive function, sleep quality, and severity and duration of delirium. The results of this study will provide suggestions for the prevention of delirium after cardiac surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: CABG; Valve Surgery; Sleep Problems; Delirium - Postoperative
• Intervention / Treatment: Other: Placebo intervention; Behavioral: Cognitive behavioral therapy intervention; Dietary supplement: Melatonin intervention

• Study Type: Interventional
• Enrollment (Estimated): 1281
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fuxia Yan; Phone Number: 010 88396628; Email: yanfuxia@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Scheduled for elective coronary artery bypass grafting and/or valve surgery.
3. Preoperative Pittsburgh Sleep Quality Index (PSQI) score ≥ 5.

Exclusion Criteria:

1. History of neurosurgery, cerebral hemorrhage, cerebral infarction, delirium, dementia, or other neurological diseases.
2. History of mental illness.
3. Habitual heavy drinking.
4. American Society of Anesthesiologists (ASA) grade IV or above.
5. Severe hepatic dysfunction (Child-Pugh Grade C) or renal dysfunction (chronic kidney disease stages 3-4).
6. Contraindications to melatonin use, such as allergies to melatonin-related ingredients.
7. Currently taking melatonin, melatonin receptor agonists, sleep-related medications, sedatives, antipsychotic medications, or opioids.
8. Inability to communicate due to hearing or speech impairment, or refusal to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Other: Placebo intervention; Patients in the placebo group need to take oral placebos of 5 mg at 30-60 minutes (administered at 21:00) before sleep, nightly, for 7 to 14 days before surgery. The placebo is provided by Guangzhou Boji Biomedical Science Park Co., LTD. (Guangzhou, Guangdong, China).
Experimental: Placebo and cognitive behavioral therapy intervention group	Other: Placebo intervention; Patients in the placebo group need to take oral placebos of 5 mg at 30-60 minutes (administered at 21:00) before sleep, nightly, for 7 to 14 days before surgery. The placebo is provided by Guangzhou Boji Biomedical Science Park Co., LTD. (Guangzhou, Guangdong, China).; Behavioral: Cognitive behavioral therapy intervention; The cognitive behavioral intervention provides sleep-related education 7-14 days before surgery. The educational content should include the following aspects: 1) Establish a consistent bedtime and wake-up time, recommending a sleep schedule from 22:00 to 07:00, and avoid prolonged daytime naps; 2) Optimize the sleep environment by ensuring a quiet setting, turning off lights, and refraining from using mobile phones, computers, and other electronic devices 30 minutes before bedtime; 3) Manage diet by avoiding caffeinated foods such as chocolate, tea, and cola; 4) Engage in appropriate daytime activities as permitted by the patient's condition.
Experimental: Melatonin and cognitive behavioral therapy intervention group	Behavioral: Cognitive behavioral therapy intervention; The cognitive behavioral intervention provides sleep-related education 7-14 days before surgery. The educational content should include the following aspects: 1) Establish a consistent bedtime and wake-up time, recommending a sleep schedule from 22:00 to 07:00, and avoid prolonged daytime naps; 2) Optimize the sleep environment by ensuring a quiet setting, turning off lights, and refraining from using mobile phones, computers, and other electronic devices 30 minutes before bedtime; 3) Manage diet by avoiding caffeinated foods such as chocolate, tea, and cola; 4) Engage in appropriate daytime activities as permitted by the patient's condition.; Dietary supplement: Melatonin intervention; Patients in the melatonin intervention group are required to take an oral melatonin of 5 mg at 30-60 minutes before sleep (administered at 21:00) nightly for 7 to 14 days before surgery. The melatonin was provided by Kangenbei Pharmaceutical Co., LTD. (Hangzhou, Zhejiang, China).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of postoperative delirium	Postoperative 7 days or before discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative sleep quality	The sleep quality was evaluated using the Actigraph model wGT3X-BT and the Sleep Quality and Nighttime Restlessness Scale (SQNRS) score. Subjects wore the Actigraph wGT3X-BT activity monitor from the beginning of their hospital admission until 7 days after surgery or before discharge. The device will record parameters such as total sleep time, wake time after falling asleep, number of awakenings, average wake time, and sleep efficiency during the first 7 days after surgery or before discharge to assess the subjects' sleep quality. Additionally, the SQNRS score was used to evaluate patients' subjective sleep quality during the same period. The SQNRS score ranges from 0 to 10, with higher scores indicating better sleep quality.	Postoperative 7 days or before discharge
Postoperative cognitive function	The Montreal Cognitive Assessment (MoCA) will be administered to evaluate the cognitive function of the patients 7 days after surgery or before discharge. The MoCA has a total score of 30 points, with a score above 26 indicating normal cognitive function.	The 7th day after surgery or before discharge
Duration and severity of delirium		Postoperative 7 days or before discharge
Postoperative mood and anxiety	The Hospital Anxiety and Depression Scale (HADS) will be utilized to evaluate the mood and anxiety levels of the patients during the first 7 days after surgery or before discharge. The HADS scale comprises two subscales, totalling 14 items: 7 items assess anxiety, and the other 7 assess depression. Each item is scored on a scale of 0 to 3, with each subscale totalling up to 21 points. Interpretation of the scores is as follows: 0-7 indicates a normal state, 8-10 suggests mild anxiety/depression, 11-14 indicates moderate anxiety/depression, and 15-21 suggests severe anxiety/depression.	The 7th day after surgery or before discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay		30 days after surgery
Postoperative pain score	The Visual Analogue Scale (VAS) will be employed to assess the pain levels of patients during the first 7 days after surgery or before discharge. A VAS score ranges from 0 to 10, with 1-3 indicating mild pain, 4-6 indicating moderate pain, and 7-10 indicating severe pain.	Postoperative 7 days or before discharge
Types and doses of postoperative sedative and analgesic drugs		Postoperative 7 days or before discharge
Postoperative nausea and vomiting	The frequency of nausea and vomiting will be recorded daily for 7 days following surgery or before discharge, as documented during bedside consultations.	Postoperative 7 days or before discharge
Postoperative markers of oxidative stress and inflammation	Within 24 hours after surgery, levels of malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA), and C-reactive protein (CRP) will be determined from 5 mL of venous blood drawn from the patients.	24 hours after surgery
Postoperative mechanical ventilation time and Intensive Care Unit stay time		Postoperative 7 days or before discharge
In-hospital mortality		Postoperative 7 days or before discharge
Serious adverse cardiovascular events		Postoperative 7 days or before discharge
Long-term survival	Survival information will be obtained through telephone follow-up.	30 days after surgery
Long-term survival	Survival information will be obtained through telephone follow-up.	12 months after surgery
Long-term sleep quality	The patients' sleep quality will be assessed through telephone follow-up using the Sleep Quality and Nighttime Restlessness Scale (SQNRS). The SQNRS score ranges from 0 to 10, with higher scores indicating better sleep quality.	30 days after surgery
Long-term sleep quality	The patients' sleep quality will be assessed through telephone follow-up using the Sleep Quality and Nighttime Restlessness Scale (SQNRS). The SQNRS score ranges from 0 to 10, with higher scores indicating better sleep quality.	12 months after surgery
Long-term pain	The patients' long-term pain will be assessed through telephone follow-up using the Visual Analogue Scale (VAS). A VAS score ranges from 0 to 10, with 1-3 indicating mild pain, 4-6 indicating moderate pain, and 7-10 indicating severe pain.	30 days after surgery
Long-term pain	The patients' long-term pain will be assessed through telephone follow-up using the Visual Analogue Scale (VAS). A VAS score ranges from 0 to 10, with 1-3 indicating mild pain, 4-6 indicating moderate pain, and 7-10 indicating severe pain.	12 months after surgery
Total hospitalization costs		30 days after surgery

Collaborators and Investigators

• Sponsor: Yan Fuxia

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Sleep Wake Disorders; Emergence Delirium; Delirium; Dyssomnias; Parasomnias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antioxidants; Protective Agents; Melatonin
• Other Study ID Numbers: 2024-2417

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
• product manufactured in and exported from the U.S.: No