A study on the effect and acting mechanism of ulinastatin on postoperative delirium in elderly patients undergoing total hip arthroplasty

ZHANG Xungong; WU Xiaoshun

doi:10.3969/j.issn.1674-3806.2024.12.10

Abstract：Objective To explore the effect and acting mechanism of ulinastatin on postoperative delirium(POD)in elderly patients undergoing total hip arthroplasty(THA).Methods A total of 192 elderly patients undergoing elective surgery of THA were recruited in the Fifth Clinical Medical College of Henan University of Chinese Medicine(People's Hospital of Zhengzhou)from August 2022 to December 2023.The patients were divided into ulinastatin group(group U)and normal saline group(group N)by using random number table method,with 96 cases in each group.In group U,5 000 U/kg of ulinastatin was injected intravenously 10 minutes before anesthesia induction until the end of surgery,and in group N,the same volume of normal saline was injected intravenously until the end of surgery.The patients were assessed for POD by using confusion assessment method-intensive care unit(CAM-ICU)and Richmond Agitation-Sedation Scale(RASS)within 3 days after surgery.Blood samples were collected 48 hours after surgery,and peripheral blood mononuclear cells(PBMCs)were isolated.The concentration of ferric ion(Fe2+),the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in PBMCs were determined by using the colorimetric method.The expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)were determined by using Western blot method.The clinical data of the patients were collected.Results In group U,the operation of 1 patient was canceled before surgery,and 1 patient underwent a second operation to stop bleeding after surgery,and 94 patients were finally included.In group N,1 patient voluntarily dropped out of the study after surgery,2 patients underwent a second operation to stop bleeding after surgery,and 93 patients were finally included.Within 3 days after surgery,the incidence of POD in group U was significantly lower than that in group N(20.21％vs 35.48％;x2=5.431,P=0.020).There were no significant differences in POD severity scores and POD duration between the two groups(P＞0.05).Compared with that in group N,the length of postoperative hospitalization in group U was significantly shortened(P＜0.05).There were no significant differences in operation time,total anesthesia time,blood loss volume,fluid intake and the duration of stay in postanesthesia care unit(PACU)between the two groups(P＞0.05).Compared with group N,group U had a decrease in Fe2+concentration and MDA content,an increase in SOD activity,a decrease in the expression of ACSL4 protein,and an increase in the expression of GPX4 protein in PBMCs 48 hours after surgery,and the differences were statistically significant(P＜0.05).There was no significant difference in the incidence of adverse events between the two groups(P＞0.05).Conclusion Ulinastatin has a neuroprotective effect,which can improve neurological dysfunction and reduce the incidence of POD in elderly patients undergoing THA.The mechanism of action may be related to inhibiting ferroptosis in PBMCs and anti-oxidative stress.