Intraoperative Dexmedetomidine Use and Postoperative Delirium After Cardiac Surgery

This hospital-based observational study comprises two linked components designed to evaluate the association between intraoperative dexmedetomidine use and postoperative delirium after cardiac surgery and to explore the potential involvement of perioperative matrix metalloproteinase-8 (MMP-8) responses.

The first component is a retrospective cohort study using routinely collected clinical data from the Tongji Hospital research data platform. Adult patients who underwent cardiac surgery between January 2015 and December 2025 will be screened according to predefined eligibility criteria. The primary exposure is intraoperative dexmedetomidine use, including whether dexmedetomidine was administered and, when available, its dose, timing, and duration. The decision to administer dexmedetomidine was made by the attending anesthesiologist based on the patient's clinical condition and routine anesthetic practice and was not assigned by the study protocol.

The primary outcome is postoperative delirium. A documented diagnosis of postoperative delirium in the medical record will be accepted as a confirmed event. For patients without an explicitly documented diagnosis, postoperative medical and nursing records will be independently reviewed by two trained researchers using standardized criteria based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Disagreements will be resolved by a third researcher. Secondary clinical outcomes include prolonged mechanical ventilation and in-hospital all-cause mortality.

The second component is a secondary biomarker analysis using archived plasma samples and linked clinical data from a previously established prospective observational cohort. Participants in the original cohort were prospectively enrolled between April and December 2023. Plasma samples were collected at three predefined perioperative time points: before surgery, at the end of surgery, and 24 hours after surgery.

The collection, storage, and use of these samples were previously approved by the Medical Ethics Committee of Tongji Hospital under Approval No. TJ-IRB20231224. For the present study, archived plasma samples will be retrieved from the Department of Anesthesiology biobank and analyzed for MMP-8 and related biomarkers under the current ethics approval, Approval No. TJ-IRB202603077. No additional blood collection or study-assigned treatment will be performed for this secondary analysis.

Patients who received intraoperative dexmedetomidine will be compared with those who did not receive dexmedetomidine. Multivariable regression models will be used to evaluate the association between dexmedetomidine use and postoperative delirium while accounting for relevant demographic, clinical, and surgical factors. Propensity score matching, subgroup analyses, interaction analyses, and sensitivity analyses will be performed to evaluate the robustness of the findings. The associations among intraoperative dexmedetomidine use, perioperative MMP-8 levels and changes, and postoperative delirium will also be examined.

Inclusion criteria

• Adults aged 18 to 80 years.
• Patients who underwent cardiac surgery with cardiopulmonary bypass at Tongji Hospital during the predefined study period.
• Availability of perioperative medication records and postoperative medical and nursing records sufficient to determine intraoperative dexmedetomidine exposure and postoperative delirium status.
• For the biomarker subcohort, availability of archived plasma samples collected preoperatively, at the end of surgery, and 24 hours postoperatively, together with linked clinical data.

Exclusion criteria

• Pregnancy.
• Inability to communicate effectively because of severe visual, auditory, or language impairment.
• Preoperative delirium or dementia.
• A history of severe psychiatric illness, including schizophrenia or severe depressive disorder.
• Long-term or high-dose use of antipsychotic medications.
• Intolerance or allergy to benzodiazepines.
• Myasthenia gravis.
• Acute stroke or severe traumatic brain injury within the preceding 6 months.
• Previous solid-organ or bone marrow transplantation.