Introduction Postoperative delirium (POD) is a common and serious postoperative complication, with an incidence of approximately 30% among older adults undergoing gastrointestinal surgery. Serotonin has been implicated in a variety of neuropsychiatric disorders. Gastrointestinal surgery has been shown to increase serotonin synthesis and release from enterochromaffin cells; however, the causal relationship between serotonin and POD remains unclear. This study aims to investigate the causal relationship between peripheral serotonin levels and POD in older adults undergoing gastrointestinal surgery. Methods and analysis This single-centre prospective cohort study will enrol 314 patients aged ≥60 years who are undergoing elective gastrointestinal surgery at the Affiliated Hospital of Qingdao University between December 2025 and December 2026. Peripheral serotonin levels will be measured prior to anaesthesia induction and prior to discharge from the post-anaesthesia care unit. The primary outcome will be the incidence of POD within 3 days. Secondary outcomes will include emergence agitation, number of POD episodes, POD onset time and duration, POD severity and subtype, pain scores, quality of recovery, gastrointestinal function and postoperative complications. A predefined directed acyclic graph will be used to guide covariate adjustment. Statistical analyses will include multivariate logistic regression, linear trend analysis, restricted cubic spline modelling, subgroup analyses, sensitivity analyses and Bayesian mediation analysis. Delirium assessors will undergo standardised training conducted by psychiatrists to ensure diagnostic reliability. Ethics and dissemination The study protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No. QYFYEC2025-199) and was registered with the Chinese Clinical Trial Registry (Registration ChiCTR2500112152). Written informed consent will be obtained from all participants prior to enrolment. Data will be anonymised, securely stored on encrypted servers for a minimum of 10 years, and shared only with approval from the ethics committee. Results will be disseminated through publication in peer-reviewed journals and presentation at scientific conferences. Trial registration number ChiCTR2500112152.
Wang et al. (Wed,) studied this question.