Effect of intranasal insulin pretreatment on postoperative delirium in patients undergoing knee arthroplasty in high-altitude areas: a single-centre, prospective, double-blind, randomised controlled clinical trial study protocol
Peng Luo, Jingzheng Zeng, Yulin Wu, Yufeng Chen, Gu Gong, Qingqing Huang, Xiaoqin LuoIntroduction
Postoperative delirium (POD) is a common and severe complication following surgery, particularly in high-altitude areas where the hypoxic environment may exacerbate cognitive dysfunction. Patients undergoing knee arthroplasty are at an increased risk of POD due to surgical stress, inflammation and ischaemia-reperfusion injury. Intranasal insulin has emerged as a promising intervention for preventing cognitive impairment by directly targeting brain insulin receptors and reducing neuroinflammation. However, its effect on POD in high-altitude surgical patients remains unexplored. This study aims to investigate whether intranasal insulin pretreatment reduces the incidence of POD in patients undergoing knee arthroplasty in high-altitude areas, providing new clinical insights for POD prevention in this specific setting.
Methods and analysis
This study is a single-centre, prospective, double-blind, randomised, placebo-controlled clinical trial. A total of 192 patients scheduled for elective knee arthroplasty under general anaesthesia in a high-altitude area will be recruited and randomly assigned to two groups (1:1 ratio) using a random number table method: the control group (0.9% normal saline nasal spray, 0.75 mL per administration) and the insulin group (rapid-acting insulin nasal spray, 30 IU/0.75 mL per administration). The intervention will be administered five times, starting 2 days before surgery (two times per day at 09:00 and 19:00), with the final dose given 10 min before anaesthesia induction. The primary outcome is the incidence of POD within the first 3 days postoperatively, assessed using the Confusion Assessment Method for the Intensive Care Unit. Secondary outcomes include cognitive function assessed by the Chinese Mini-Mental Status at 1 month postoperatively, pain scores (visual analogue scale) on postoperative days 1–3 and the incidence of adverse events (eg, nasal irritation, hypoglycaemia). Exploratory outcomes include serum concentrations of inflammatory markers (interleukin-1β, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, monocyte chemoattractant protein-1) measured before the first intervention, at the end of surgery and on postoperative days 1–3.
Ethics and dissemination
The trial protocol has been approved by the Clinical Research Ethics Committee of the Ganzi Tibetan Autonomous Prefecture People’s Hospital (identifier: GZZYY-2025-06-17-3). The findings of this trial will be disseminated through peer-reviewed journal publications and presented at national or international academic conferences to guide future clinical practice.
Trial registration number
ChiCTR2500107937