Transcranial Magnetic Stimulation and Perioperative Neurocognitive Disorders

Study Overview
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Brief Summary
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To investigate the impact of rTMS on the incidence of perioperative neurocognitive disorders in patients after after cardiac surgerysurgery. To explore the underlying mechanisms behind the efficacy.

Detailed Description
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There is a relatively high incidence of perioperative neurocognitive disorders（PND） after surgeries, and the incidence is even higher in the geriatric population undergoing cardiac surgery. Nevertheless, there remains no effective medication or intervention been approved in PND. It has been shown that brain stimulation can improve cognitive function in mild cognitively impaired patients. However, the effects on cognitive function in PND remain uninvestigated.

Official Title
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The Effects of rTMS on Postoperative Cognitive Function in Patients After Cardiac Surgery

Conditions
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Postoperative Cognitive Dysfunction, Repetitive Transcranial Magnetic Stimulation

Intervention / Treatment
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* Procedure: repetitive transcranial magnetic stimulation
* Procedure: Sham Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18 years or older. 2. ASA class I - III, patients undergoing elective cardiac surgery(coronary artery bypass grafting, aortic or mitral valve surgery). 3. Sign the informed consent. 4. Able to complete follow-up visits. Exclusion Criteria: 1. A history of psychopathology and/or taking medication. 2. Previous history of neurological disease. 3. Severe organic diseases. 4. RTMS contraindications (such as a history of epileptic seizures, metal implants near the head). 5. Having delirium, assessed by CAM, before surgery. 6. Participating in other clinical studies at the time of screening. 7. Having a cardiopulmonary arrest and cardiopulmonary resuscitation. 8. Having short-term second operation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active rTMS Group<br>A stimulation set will be administered to each participant in the rTMS group with 15 sessions stimulation for total five days after surgery. | Procedure: repetitive transcranial magnetic stimulation<br>* The rTMS mode consists of a cluster stimulus delivered every 0.2 seconds (5 Hz), with each cluster stimulus consisting of three burst stimuli with a 50 Hz body frequency. The duration of a single stimulus was approximately 40 seconds, for a total of 600 pulses. Stimulation takes place bilaterally in the dorsolateral prefrontal cortex (DLPFC). All enrolled patient in the rTMS group will receive 1 set simulation per day with an intersession interval (ISI) of over 30 minutes on postoperative day 1 to 5 after the surgery.<br>|
| Sham Comparator: Sham Stimulation Group<br>Patients randomly assigned to sham group will receive 15 sessions sham stimulation for total five days after surgery. | Procedure: Sham Stimulation<br>* Shaman stimulation uses the same protocol (600 pulses per session, 3 sessions per set, ISI≥30 min, 3 sets) with the coil set at 90 against the skull on postoperative day 1 to 5 after the surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of PND on the postoperative day 30 | Incidence of PND on the postoperative day 7 and day 30 will be defined according to the MOCA and MMSE. | Within 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative delirium incidence | Incidence of postoperative delirium on postoperative day 1 to 7 will be defined by the Confusion Assessment Method for The Intensive Care Unit (CAM-ICU) or CAM | Within 7 days after surgery | 
| Perioperative pain | This will be assessed by using Visual Analogue Scale (VAS). The patients scored according to the severity of their pain from no pain (0) to most painful (10). | Within 7 days after surgery | 
| Sleep quality | We will use the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. PSQI uses a 19-item questionnaire to assess sleep quality over one month30. An increased score indicates poor quality sleep. PSQI will be recorded at different points of time as follows： 1 day before surgery 7 days after surgery 30 days after surgery | Within 30 days after surgery | 
| Depressive symptom | Depressive disorder and depression symptom severity will be measured using the 9-item patient health questionnaire (PHQ-9). It is self-administered and carries a score ranging from 0 to 27, with a score range of 0 to 3. Five, ten, fifteen, and twenty are the thresholds for mild, moderate, and moderately severe depression. | Within 7 days after surgery | 
| Activities of daily living（ADL） | As part of the pre-surgery and post-surgery evaluations, the Chinese version of the ADL scale will be used, including a Physical Self-Maintenance Scale and an Instrumental ADL scale. ADL consists of 14 items, and the total score ranges between 14 and 56 points, with higher scores indicating a lower level of functioning. ADL will be evaluated at different points of time as follows： 1 day before surgery 7 days after surgery 30 days after surgery | Within 30 days after surgery | 
| Length of hospital stay | A hospital length of stay is the number of days the patient spends in the hospital following surgery. | From the date of admission until discharged from hospital, up to 30 days | 
| Length of ICU stay | Similarly, the ICU length of stay was defined as the number of days the patient spent in the ICU before transferring to a general inpatient cardiac surgery ward | From the date of admission until discharged from ICU, up to 30 days | 
| EEG characteristics | Electroencephalography will be recorded at different points of time as follows and EEG characteristics including power in alpha, beta, theta, delta, gamma, spectrum will be extracted using MATLAB. In addition, functional brain connectivity and brain network will be assessed at different points of time as follows： before anesthesia introduction during anesthesia on the 1th dayday after surgery on the 7th day after surgery on the 30th day after surgery | Within 30 days after surgery | 
| Incidence of major adverse cardiac and cerebral events | MACCE comprises all-cause mortality, myocardial infarction, repeat unplanned revascularization (surgical revision or percutaneous transluminal coronary angioplasty), and stroke | Within 30 days after surgery |