NCT07537725

EEG-TMS for Postoperative Delirium After Cardiac Surgery

Transcranial Magnetic Stimulation for Postoperative Delirium After Cardiac Surgery: A Prospective, Single-Center, Randomized Double-Blind Controlled Study

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 144 (estimated)
• Sponsor: RenJi Hospital · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, single-center, randomized, double-blind, sham-controlled trial evaluating the safety and efficacy of transcranial magnetic stimulation (TMS) for the treatment of postoperative delirium in patients undergoing cardiac surgery with extracorporeal circulation. Eligible patients aged 50 years or older who develop delirium after surgery, as assessed by the CAM-ICU, will be randomized to receive either active TMS or sham stimulation. The intervention consists of three daily cycles of intermittent and continuous theta burst stimulation over five days. The primary outcome is the duration of delirium within the five-day intervention period. Secondary outcomes include delirium severity, time to successful discharge, and survival at 30 and 90 days. A total of 144 participants will be enrolled.

Detailed description

Postoperative delirium (POD) is a common and serious complication following cardiac surgery, associated with prolonged hospitalization, cognitive decline, and increased mortality. Currently, no specific pharmacological therapy has demonstrated consistent efficacy for POD. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that can modulate cortical excitability and has shown preliminary promise in treating delirium, potentially through mechanisms involving neuroinflammation modulation and enhancement of neural connectivity. This is a prospective, single-center, randomized, double-blind, sham-controlled trial designed to evaluate the safety and efficacy of theta burst stimulation (TBS), a patterned form of TMS, for the treatment of POD in patients undergoing cardiac surgery with extracorporeal circulation. Patients are screened preoperatively. Those who meet eligibility criteria and provide informed consent undergo baseline assessments, including high-density electroencephalography (HD-EEG) and a battery of neuropsychological and patient-reported outcome measures (cognition, sleep quality, stress, anxiety, depression, and pain). Postoperatively, all patients are assessed twice daily (at least 6 hours apart) for delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Delirium severity is assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98). Upon the first positive CAM-ICU assessment, patients are randomly assigned in a 1:1 ratio to either the active TMS group or the sham stimulation group. An independent statistical unit generates the randomization sequence. To ensure allocation concealment and blinding, each participant receives a unique anonymous treatment code. A research nurse not involved in recruitment, treatment, or outcome assessment prepares the coil (active or sham side) based on a sealed allocation table, without the presence of the treating operator. The operator knows only the treatment code and cannot distinguish the coil's active side from the sham side by appearance, device interface, or procedural feedback. Outcome assessors, patients, and statisticians remain blinded throughout the study. The intervention period lasts a maximum of 5 days. For participants in the active TMS group, each daily session consists of three cycles of TBS delivered using a 12 cm coil. Each cycle includes intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (600 pulses, 3 repetitions, approximately 10 minutes), followed 30 minutes later by continuous TBS (cTBS) applied to the right dorsolateral prefrontal cortex (600 pulses, 3 repetitions, approximately 2 minutes). Stimulation intensity is set at 80% of the resting motor threshold. Cycles are separated by 15-minute intervals. Participants in the sham group undergo an identical procedure using a sham coil that produces similar auditory and scalp sensations but delivers no electromagnetic penetration to the brain. If a participant has two consecutive negative CAM-ICU assessments during the 5-day period, stimulation is paused. It is resumed if delirium recurs. The intervention is permanently discontinued if the participant develops new-onset coma due to structural brain disease or a life-threatening serious adverse event deemed related to the intervention. Participants transferred out of the intensive care unit during the intervention period continue to receive the assigned stimulation and assessments. Those who are re-hospitalized within the 90-day follow-up and develop delirium again will continue to receive their assigned intervention. A tiered rescue medication protocol is implemented for both groups to manage uncontrollable delirium while ensuring participant safety. First-line non-pharmacological interventions are prioritized for mild cases. If pharmacological intervention is required, dexmedetomidine is the first-line agent, followed by haloperidol or quetiapine. Benzodiazepines and propofol are reserved for severe agitation or emergency situations. All rescue medication use is documented in the case report form. Data collection includes baseline demographic and clinical characteristics, intraoperative details, daily delirium assessments, vital signs during stimulation sessions, and adverse events. Post-discharge follow-up occurs at 30 and 90 days to assess survival and neuropsychological outcomes. The primary analysis will compare the duration of delirium within the 5-day intervention period between groups using linear regression models adjusted for predefined covariates. A sample size of 144 participants (72 per group) provides 80% power to detect a clinically meaningful difference in delirium duration, assuming a two-sided alpha of 0.05 and accounting for an anticipated 5% dropout rate.

Conditions

• Delirium

Interventions

Type	Name	Description
DEVICE	Theta Burst Stimulation (TBS)	A patterned form of transcranial magnetic stimulation delivered via a 12 cm coil. The active intervention consists of intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex and continuous TBS (cTBS) applied to the right dorsolateral prefrontal cortex at 80% of resting motor threshold.
DEVICE	Sham Stimulation	Sham stimulation delivered using a coil identical in appearance to the active coil, which produces similar auditory and scalp sensations but delivers no electromagnetic penetration to the brain.

Timeline

• Start date: 2026-04-27
• Primary completion: 2026-12-30
• Completion: 2027-03-31
• First posted: 2026-04-17
• Last updated: 2026-04-17