Repeated Preoperative Intranasal Administration of Insulin Decreases the Incidence of Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Radical Gastrointestinal Surgery: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study

Abstract

Study ObjectivesThis study aimed to investigate the effects of repeated preoperative intranasal administration of insulin on the incidence of postoperative delirium (POD) and the levels of serum pro-inflammatory markers in elderly patients undergoing laparoscopic radical gastrointestinal surgery. DesignProspective, randomized, double-blinded, placebo-controlled clinical study. SettingGeneral Hospital of Western Theater Command from August 2019 to December 2019. PatientsNinety elderly patients underwent laparoscopic radical gastrointestinal tumor resections under general anesthesia. InterventionsPatients were randomly divided into a control group (0.5 mL saline administered intranasally) or an insulin group (20 U/0.5 mL insulin administered intranasally) for 2 days prior to surgery, with 45 patients in each group. MeasurementsThe incidence of delirium was measured at postoperative day 1 (T2), day 3 (T3), and day 5 (T4) using the Confusion Assessment Method for the intensive care unit (CAM-ICU). Plasma levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured at T0 (before insulin or saline administration), T1 (at the end of surgery), T2, T3, and T4 by enzyme-linked immunosorbent assay. Main ResultsCompared with the control group, the insulin group demonstrated a decreased POD incidence (12.5% vs. 47.5%, p = 0.001) within 5 days after surgery. The incidence of POD was significantly lower in the Ins group than in the Con group at T2 (12.5% vs. 32.5%, p = 0.032) and at T3 (2.5% vs. 20%, p = 0.034). The incidence of POD decreased in both groups over time and was similar at T4 (0% vs 10%, p = 0.116). Compared with the baseline value at T0, serum TNF-α, IL-6 and IL-1β concentrations increased significantly at T1-4 (p <0.05). Compared with the control group at the same time point, the expression levels of TNF-α, IL-6 and IL-1β in group I at T2 and T3 were significantly reduced (p <0.05). The incidence rates of adverse events were similar in the two groups. ConclusionsRepeated preoperative intranasal administration of insulin prevented the occurrence of delirium after laparoscopic radical gastrointestinal surgery in elderly patients and reduced TNF-α, IL-1β, and IL-6 levels.