Abstract
OBJECTIVE: Postoperative delirium (POD) frequently occurs among elderly patients following surgery, yet effective preventive measures remain insufficiently established. This study aimed to investigate whether perioperative intranasal insulin (INI) administration could reduce the incidence of POD and modulate inflammatory marker levels in elderly patients undergoing hip fracture surgery under general anesthesia (GA). METHODS: From June to December 2024, a total of 96 elderly patients scheduled for hip fracture surgery with GA were enrolled and randomly assigned to two groups (48 per group). Patients in the insulin group received INI (20 units in 0.5 mL) twice daily, beginning two days preoperatively and continuing for five days. Patients in the control group received an equivalent volume of saline (0.5 mL) with the same dosing regimen. The primary outcome was POD incidence within five postoperative days, evaluated using the 3D-CAM-CN assessment tool. Secondary outcomes included serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP), measured at baseline (T0; before intervention) and postoperative day 1 (T1) using immunofluorescence quantitative assays. RESULTS: Ninety-two patients completed the study, with an overall POD incidence rate of 20.7%. Patients treated with INI showed a significantly lower incidence of POD within the 5-day postoperative period (10.9% vs. 30.4%, P = 0.020). On postoperative day 3 (T2), the incidence of POD was notably reduced in the insulin group (2.2% vs. 19.6%, P = 0.007). No significant differences in POD incidence were observed on postoperative days 1 (T1) or 5 (T3). Serum IL-6 and CRP levels at T1 were lower in the insulin group compared to controls (P < 0.001), although both groups experienced significant elevations in these markers at T1 compared to baseline (T0) (P < 0.001). No adverse events related to interventions occurred during the study. CONCLUSION: Perioperative INI administration reduced the incidence of POD and decreased postoperative inflammatory markers (IL-6 and CRP) in elderly patients undergoing hip fracture surgery with GA. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2400085627, registration date on 14/6/2024).