Continuous Theta Burst Stimulation (cTBS) and Postoperative Delirium

Study Overview
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Brief Summary
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To investigate the impact of cTBS on the incidence of postoperative delirium and changes of cognitive function in elderly patients after surgery. To explore whether short-term cTBS can reduce the risk of postoperative delirium as a preventive strategy.

Detailed Description
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Postoperative delirium is the most common postoperative complications among elderly. Nevertheless, there remains no effective medication or intervention been approved in postoperative delirium. Recent research suggests that continuous theta burst stimulation (cTBS) has shown positive effect on improving global cognitive function in multiple mental disorders. However, the effects on cognitive function in postoperative delirium remain uninvestigated.

Official Title
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Effect of Continuous Theta Burst Stimulation (cTBS) on Postoperative Delirium

Conditions
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Transcranial Magnetic Stimulation, Repetitive, Postoperative Delirium

Intervention / Treatment
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* Device: Continuous theta burst stimulation (cTBS)
* Device: Sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years; Being scheduled to undergo an elective surgery (≥3 hours, general anesthesia) (e.g., hip replacement or open reduction with internal fixation surgery for the repair of hip fractures); Being able to complete cognitive assessment and confusion assessment methods (CAM); Having normal cognitive function at the time of enrollment, e.g., Mini-Mental State Examination (MMSE) scores above 24; Chinese Mandarin as the native language; Willing to participate and being competent to provide informed consent. Exclusion Criteria: Having preoperative delirium assessed by CAM; Having brain tumor, stroke, or mental disorders (e.g., depression or dementia); Having contraindications of cTBS (e.g., head trauma, history of epilepsy or metal implants in the head or heart); Participating in other clinical studies.

Ages Eligible for Study
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Minimum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cTBS group<br>Patients randomly assigned to cTBS group will receive 12 sessions cTBS for total four days after surgery. | Device: Continuous theta burst stimulation (cTBS)<br>* Our active treatment will consist of 600 pulses per session, delivered over the right dorsolateral prefrontal cortex at 80% of resting motor threshold (RMT). Every session cTBS consists of 50 Hz triplets of pulses delivered at 5 Hz for 40 seconds for a total of 600 pulses. Every set simulation includes 3 sessions. All enrolled patient in the cTBS group will receive 1 set simulation per day with an intersession interval (ISI) of over 30 minutes during the hospitalization after the surgery. The first set of stimulation will be given at 4 hours after the end of surgery on the day of surgery. The other sets of stimulation will be given at 8 am, 8:30 am and 9:00 am on postoperative day 1,2 and 3, respectively.<br>|
| Sham Comparator: sham group<br>Patients randomly assigned to sham group will receive 12 sessions sham stimulation for total four days after surgery. | Device: Sham stimulation<br>* The sham stimulation group will receive a sham cTBS (600 pulses per session, 3 sessions per day, ISI ≥ 30mins, 4 days) with the coil set at 90 against the skull. The first set of stimulation will be given at 4 hours after the end of surgery on the day of surgery. The other sets of stimulation will be given at 8 am, 8:30 am and 9:00 am on postoperative day 1,2 and 3, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative delirium | Incidence of postoperative delirium on postoperative day 1, 2 and 3 will be defined according to the confusion assessment methods (CAM). | 3 days after surgery | 
| Cognitive function related to delirium | The cognitive function related to delirium will be assessed by using Delirium Symptom Interview Daily (DSI Daily). | 3 days after surgery | 
| Severity of postoperative delirium | Severity of postoperative delirium on postoperative day 1, 2 and 3 will be defined according to he Confusion Assessment Method based delirium severity evaluation tool (CAM-S).The sum score of CAM-S ranges from 0 (no) to 19 (most severe). | 3 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain level | 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). | up to 7 days after anesthesia/surgery | 
| Sleep quality | This will be assessed by using Pittsburgh Sleep Quality Index (PSQI).The global PSQI score ranges from 0 to 21, where lower scores denote a healthier sleep quality. | up to 7 days after anesthesia/surgery | 
| Ability of daily living | This will be assessed by using Chinese version of Activity of Daily Living (ADL) Scale.The total score of ADLs ranges from 14 to 56 points and higher ADLs scores indicate lower activities of daily living. | up to 7 days after anesthesia/surgery | 
| Rate of complication and mortality | Rate of complication and mortality during the stay in hospital or up to 7 days after anesthesia/surgery, depending which one is longer | up to 7 days after anesthesia/surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative delirium, continuous theta burst stimulation