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.

INTRODUCTION

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.