Effects of Intranasal Dexmedetomidine on the Night Before Surgery on Postoperative Delirium in Elderly Patients Undergoing Total Knee/Hip Arthroplasty. A Parallel-Arm, Randomized Controlled, Non-Inferiority Trial

Abstract

Importance It is crucial to identify preoperative treatment methods that can safely and effectively reduce the incidence of postoperative delirium. Objective To evaluate whether preoperative intranasal dexmedetomidine administration for preventing postoperative delirium is non-inferior to intravenous dexmedetomidine infusion on the operative day before induction for elderly patients undergoing elective knee/hip arthroplasty. Design This randomized clinical trial was performed at a tertiary hospital in China between January 10, 2025 to August 30, 2025. The follow-up for the last subject was completed on September 6, 2025. Setting This was a single center trial. Participants After qualification screening, 535 patients scheduled for unilateral total knee arthroplasty and total hip arthroplasty under general anesthesia were invited to participate in the study. Ultimately, 316 patients were randomly assigned to the experimental group and the control group. Interventions Patients were randomized to receive intranasal dexmedetomidine (the night before surgery)+intravenous normal saline (before induction) or intranasal normal saline (the night before surgery)+intravenous dexmedetomidine (before induction). Main Outcomes and Measures The primary outcome was incidence of postoperative delirium within 3 days after surgery assessed by the Confusion Assessment Method. Results In the intention-to-treat analysis, the incidence of postoperative delirium within 3 days was 9.5% in experimental group and 7.6% in control group. The rate difference was 0.02 (95% CI: −0.04 to 0.08), meeting the pre-specified non-inferiority criterion (P < 0.001). Patients in experimental group showed significantly improved sleep quality on the night before surgery and lower preoperative anxiety and pain scores. Furthermore, the incidence of adverse events was significantly lower in experimental group. Conclusions and Relevance For elderly patients undergoing major joint arthroplasty, intranasal dexmedetomidine administered the night before surgery is non-inferior to pre-induction intravenous infusion for preventing postoperative delirium. The intranasal route offers additional benefits, including improved preoperative sleep, reduced anxiety, and superior hemodynamic stability.