Remimazolam for Reducing Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Gastrectomy

This prospective, single-center, randomized, participant- and outcome assessor-blinded, parallel-group controlled trial was conducted at the First Affiliated Hospital of Nanjing Medical University between January 21 and August 5, 2026. Patients aged 65 years or older who were scheduled to undergo elective laparoscopic radical gastrectomy for gastric cancer were screened for eligibility. A total of 147 participants were randomized in a 1:1 ratio to receive either remimazolam-based anesthesia or propofol-midazolam-based anesthesia. Randomization was based on a computer-generated sequence, with allocation concealed using sequentially numbered, opaque, sealed envelopes. Participants and postoperative outcome assessors were blinded to treatment allocation, whereas the attending anesthesiologists administering the allocated anesthetic regimen were not blinded.

Standardized perioperative monitoring and management were applied in both groups, including bispectral index-guided anesthetic depth control, opioid analgesia, neuromuscular blockade, controlled ventilation, vasoactive medication titration, and postoperative patient-controlled intravenous analgesia. Postoperative delirium was assessed once daily between 14:00 and 17:00 on postoperative days 1-3. Ward patients were assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method, whereas patients admitted to the intensive care unit were assessed using the Confusion Assessment Method for the Intensive Care Unit.

The original protocol specified standardized delirium assessment through postoperative day 5. Owing to limited research personnel during trial implementation, standardized assessments could only be consistently completed through postoperative day 3. Therefore, the primary outcome was the cumulative incidence of POD during postoperative days 1-3, and no assumptions were made regarding delirium status on postoperative days 4 and 5. Secondary outcomes included post-induction hypotension, maximum reduction in mean arterial pressure from baseline, peri-induction vasoactive drug requirements, peri-induction mean arterial pressure, heart rate and bispectral index trajectories, time to extubation, length of stay in the post-anesthesia care unit and hospital, postoperative pain scores, postoperative nausea and vomiting, PACU hypoxemia, emergence agitation, unplanned intensive care unit admission, and postoperative pulmonary infection.

Inclusion criteria

• Age ≥ 65 years.
• Body mass index (BMI) between 18 and 28 kg/m².
• ASA physical status I-III.
• Scheduled for elective laparoscopic radical gastrectomy under general anesthesia at Jiangsu Province Hospital.
• Able and willing to sign informed consent.

Exclusion criteria

• Severe respiratory, cardiovascular, renal, or hepatic dysfunction.
• Stroke within the past 6 months or other central nervous system diseases.
• History of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or other psychiatric disorders.
• History of alcohol abuse or psychoactive substance dependence.
• Severe visual, hearing, or language impairment preventing communication.
• Allergy or contraindication to propofol or benzodiazepines.
• Preoperative cognitive impairment assessed by MMSE (≤24 for ≥middle-school education; ≤20 for primary school; ≤17 for no formal education).
• Participation in another drug clinical trial within 1 month before surgery.