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

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.