Intraoperative Dexmedetomidine Use, MMP-8, and Postoperative Delirium After Cardiac Surgery With Cardiopulmonary Bypass

This hospital-based observational study comprised two linked clinical components designed to evaluate the association between intraoperative dexmedetomidine use and postoperative delirium (POD) after cardiac surgery with cardiopulmonary bypass (CPB) and to explore the clinical relevance of perioperative matrix metalloproteinase-8 (MMP-8) responses.

The first component was a retrospective multicampus cohort study using routinely collected clinical data from three campuses of Tongji Hospital. Adult patients undergoing cardiac surgery with CPB between January 2015 and December 2022 were screened according to predefined eligibility criteria. The primary exposure was intraoperative dexmedetomidine administration by continuous intravenous infusion, ascertained from anesthesia records. Dexmedetomidine administration was determined by the attending anesthesiologist according to clinical judgment and routine anesthetic practice and was not assigned by the study protocol. The primary outcome was POD occurring within 7 days after surgery. Documented POD diagnoses were accepted as confirmed events; when no explicit diagnosis was documented, postoperative medical and nursing records were retrospectively reviewed by trained anesthesiologists and intensivists blinded to intraoperative dexmedetomidine exposure. Secondary outcomes included in-hospital mortality and hospital length of stay. Multivariable regression, propensity score matching, subgroup and interaction analyses, and E-value analysis were used to evaluate the robustness of the dexmedetomidine-POD association.

The second component used archived plasma samples and linked clinical data from a previously established prospective observational cohort of adults undergoing cardiac surgery with CPB who were enrolled between April 2023 and September 2024. In the original cohort, intraoperative dexmedetomidine use was determined by the treating anesthesiologist and was not influenced by the study investigators. POD within 7 days after surgery was prospectively assessed, and participants were followed until hospital discharge. Plasma samples had been collected preoperatively, at the end of surgery, and 24 h postoperatively and stored for subsequent analyses. The original prospective cohort enrollment and perioperative biospecimen collection were approved by the Medical Ethics Committee of Tongji Hospital under Approval No. TJ-IRB20231224. The current study, including secondary analyses of archived clinical data and plasma samples, was subsequently approved under Approval No. TJ-IRB202603077. Archived plasma samples were analyzed for MMP-8, and perioperative MMP-8 levels and changes were evaluated in relation to dexmedetomidine exposure and POD. Additional analyses assessed the discriminatory value of perioperative MMP-8 measures for POD and their potential statistical mediating role in the association between intraoperative dexmedetomidine use and POD.

Inclusion criteria

• Adults aged 18 years or older.
• Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).
• For the retrospective cohort, eligible patients undergoing cardiac surgery with CPB at the three participating campuses of Tongji Hospital between January 2015 and December 2022.
• For the prospective biomarker cohort, eligible participants enrolled between April 2023 and September 2024 with archived plasma samples collected preoperatively, at the end of surgery, and 24 h postoperatively, together with linked clinical data.

Exclusion criteria

• Conditions precluding dexmedetomidine use, including second- or third-degree atrioventricular block without a pacemaker, uncontrolled hypotension, acute cerebrovascular disease, or known hypersensitivity to dexmedetomidine.
• Severe neurological or psychiatric disorders, including a history of treatment for severe mental illness.
• Inability to communicate effectively because of severe hearing, visual, or speech impairments.
• Pregnancy or breastfeeding.
• Emergency surgery.