The relationship between postoperative delirium development and zonulin and interleukin-8 in patients undergoing femoral fracture operation under regional anesthesia

Aims: Postoperative delirium (POD) is a common complication in geriatric patients undergoing orthopedic surgery for hip fractures. Inflammatory cytokines crossing the blood-brain barrier were shown to play a role in the pathophysiology. Zonulin which a signal protein that reversibly modulates tight intercellular junction may affect the blood-brain barrier. It was shown to have a strong association with the development of diseases such as autism and major depressive disorder. Interleukin-8 (IL-8), which crosses the blood-brain barrier in inflammatory conditions, is tought to play a role in the development of POD by disrupting neurocognitive functions. In this study, it was aimed to evaluate the relationship between POD and blood zonulin and IL-8 levels in elderly patients who underwent surgery for hip fractures. Materials and Methods: Patients who were over 65 years of age, ASA II-III and scheduled for major surgery for hip fractures were included in the study. All patients were preoperatively evaluated with standardized mini mental test and modified fragility index and first blood samples were taken for the measurements of zonulin and IL-8 levels. Patients were operated under regional anesthesia and Delirium Rating Scale (DDS) scores were recorded at the 1st, 2nd and 3rd postoperative days. The patients who developed delirium were included in the "Delirium" group and the second blood samples were taken at the time of diagnosis. Patients who did not develop POD in the postoperative first 72 hours were included in the "control" group and the second blood samples were taken then. Postoperative pain scores of the patients were recorded by using a numerical rating scale (NRS). Results: A total of 73 patients were included in the study. The mean age was 85 years in delirium group (n=34) and 81 years in control group (n=39). DDS scores were higher in delirium group compared to control group (p<0.001). Preoperative zonulin levels were measured 38.3±9 ng ml-1 in delirium group and 29.4±6 ng ml-1 in control group (p <0.001). Similarly, postoperative zonulin level was measured 39.9 ng ml-1 in delirium group and 30.4±8 ng ml-1 in control group (p <0.001). Preoperative IL-8 level was measured as 352±108 ng l-1 in delirium group and 387±85 ng l-1 in control group (p = 0.126). Postoperative IL-8 level was measured as 337.9±91 ng l-1 in delirium group and 398.5±83 ng l-1 in control group (p = 0.004). Pain scores of the patients were found similar at the 0., 12. and 24. postoperative hours (p = 0.218, p = 0.902, p = 0.926, respectively). Conclusion: A positively directed correlation was found between the blood zonulin levels and POD in elderly patients who underwent major surgery due to hip fracture. As a result of these data, we think that preoperatively evaluated blood zonulin level in elderly patients may be a usefull biomarker in predicting the risk of POD development. Keywords: Femur fracture, interleukin-8, postoperative delirium, zonulin. This thesis was funded by the Scientific Research Projects Coordination Unit of Muğla Sıtkı Koçman University with the project number 20/107/02/3/4.