Effect Of Remote Ischemic Preconditioning Combined With Postconditioning On Postoperative Delirium In Elderly Patients Undergoing Lower Extremity Surgery With Tourniquet

Background:Postoperative delirium（POD）is a common postoperative neurological complication that can lead to extremely high mortality,cognitive impairment,and affect prognosis.The pathogenesis of POD is still unclear,and elderly patients belong to a high-risk group.Elderly patients undergoing orthopaedic surgery are more likely to develop POD,so brain injury in elderly patients after orthopaedic surgery is still a clinical concern.Elderly patients undergoing orthopaedic surgery have a higher risk of postoperative neurological damage and a higher incidence of POD,which have great adverse consequences on the clinical prognosis and quality of life of patients.Therefore,it is necessary to find one or more interventions to prevent POD in elderly patients undergoing orthopaedic surgery.Remote ischemic preconditioning（RIC）including remote ischemic preconditioning（RIPC）and remote ischemic postconditioning（RIPostC）have been widely reported to prevent ischemia-reperfusion injury in various organs such as the heart,brain,and skeletal muscle..However,the clinical application of RIC is limited in the treatment of myocardial infarction and stroke.Many studies have not only demonstrated the promising clinical application of RIC,but also investigated its mechanism of action in animal models.Because the protective effect of RIPC+RIPostC on the brain during orthopedic surgery is controversial,and therefore,this study aims to investigate the effect of RIPC+RIPostC on serum nerve injury biomarkers S100βprotein,neuronal characteristic enolase（NSE）and POD in elderly patients undergoing lower extremity tourniquet surgery,in order to provide reference for clinical practice.Objective:This study aimed to investigate the effect of RIPC+RIPostC on nerve injury markers and postoperative delirium（POD）during lower extremity tourniquet surgery in elderly patients.Methods:Eighty elderly patients with any gender,aged 65-80 who underwent elective unicompartmental knee arthroplasty in the operating room of our hospital from February 2021to December 2021 were recruited.The American Society of Anesthesiologists（ASA）)Grade II to III.According to the random number table method,the patients were divided into the control group（Control group）and the remote ischemic preconditioning combined with postconditioning group（RIPC+RIPostC group）,with 40 cases in each group.In the RIPC+RIPostC group,RIPC was performed 30 minutes before tourniquet inflation,and RIPostC was performed 30 minutes before tourniquet inflation.The specific treatment measures are as follows:tie an inflatable cuff to the lower limb of the patient,inflate and pressurize until the pressure reaches 200 mm Hg,hold for 5 minutes,and then completely deflate the cuff until the pressure reaches 0;after 5 minutes,inflate and pressurize again,and a total of 3 cycles were performed;in group C,the cuff was tied to the lower limb of the patient’s unaffected side,but inflation and deflation were not performed.Peripheral venous blood was drawn Before tourniquet inflation（T₀）and 15 min after tourniquet inflation（T₁）,12 h（T₂）,24 h（T₃）,48 h（T₄）,5 d（T₅）and 7 d（T₆）and the concentrations of nerve injury marker-specific protein 100β（S100βprotein）and neuron-specific enolase（NSE）in serum were determined by enzyme-linked immunosorbent assay（ELISA）.Peripheral venous blood was drawn 1 day before operation and 1 day and 3 days after operation,and serum inflammatory factors（tumor necrosis factor-α（TNF-α）,interleukin-6（IL-6）and interleukin-8）were measured.（IL-8）]concentration.POD was assessed by the intensive care unit（ICU）consciousness disturbance assessment method（CAM-ICU）within 3 days after the operation.At the time point of delirium assessment,postoperative sedation was assessed by the modified Ramsay sedation scale（1-6）,postoperative analgesia was assessed by visual analogue scale（VAS）for pain,and the facial anxiety scale was used to assess peripheral pain.Perioperative anxiety and depression levels were assessed using the Hospital Anxiety and Depression Scale（HADS）.Neurocognitive testing was performed preoperatively,at discharge,and 3 months postoperatively,and postoperative cognitive dysfunction（POCD）and dementia（AD）were assessed using the Mini-Mental State Examination Scale（MMSE）,with exclusion of preoperative Patients with<24 points.Any postoperative adverse events,such as intraoperative bradykinesia or hypotension/hypertension,postoperative infection,etc.,were recorded.The 90-day mortality and length of hospital stay were recorded.After 3 months,data related to sleep,quality of life,anxiety and pain were collected using questionnaires.Results:1.Comparison of baseline clinical data of the two groups of patients The baseline data of the two groups included age,body mass index（BMI）,ASA classification,sex composition ratio,left ventricular ejection fraction（LVEF）,smoking history,drinking history,and preoperative blood gas analysis results,the number of cases of abnormal pulmonary function before operation and the basic blood oxygen saturation were similar（P>0.05）.2.Comparison of intraoperative surgery and anesthesia parameters between the two groups Compared with the Control group,the post-anesthesia monitoring and treatment room（PACU）stay time of patients in the RIPC+RIPostC group was significantly shortened（P<0.05）.Tourniquet usage time,operation time,total anesthesia time,blood loss and fluid intake were similar between the two groups（P>0.05）.3.Comparison of the levels of serum nerve markers in the two groups compared with that at T₀,the levels of serum nerve injury markers S100βand NSE in the two groups were significantly increased from T₁ to T₆,and with the prolongation of time,the levels of serum S100βand NSE in the two groups were significantly increased.were gradually increased（P<0.05）.From T₁ to T₆,compared with the Control group,the levels of serological nerve injury markers S100βand NSE in the RIPC+RIPostC group were significantly decreased（P<0.05）.4.Comparison of serum inflammatory factor concentrations between the two groups There was no statistical difference in the levels of serum TNF-α,IL-6,and IL-8 between the two groups before surgery（P>0.05）.The serum levels of TNF-α,IL-6 and IL-8 were higher than those before operation,but significantly lower in RIPC+RIPostC group than in Control group（P<0.05）.5.Comparison of postoperative sedation and analgesia scores between the two groups:VAS scores and Ramsay sedation scores at different time points after surgery were similar between the two groups,and there was no significant difference between the two groups（P>0.05）.6.All the subjects in this study passed the research protocol,and no one was lost to follow-up.A total of 13 patients（32.5%）in the Control group developed POD within 3 days after surgery,and 27 patients（67.5%）did not develop POD.In the RIPC+RIPostC group,a total of 5 patients（12.5%）developed POD within 3 days after surgery,and 35 patients（87.5%）did not develop POD.There was no difference in the severity of postoperative delirium between the two groups,and there was no difference in the mean duration（SD）of delirium between the RIPC+RIPostC group and the Control group,which were 2.00（1.41）days and0.89（0.94）days,respectively,P>0.05.7.The median（IQR[range]）of the baseline MMSE was 29（28-30[25-30]）in the RIPC+RIPostC group and 29（28-29[26-30]）in the Control group.At the 90-day follow-up after surgery,there was no difference in the MMSE score compared with the baseline examination,P>0.05.A total of 4 patients（10%）developed neurocognitive dysfunction after surgery.There was no difference in the incidence of POCD between the two groups,P>0.05.The incidence of POCD was not influenced by gender,ASA physical status,occurrence of postoperative delirium,or other perioperative factors such as educational status and MMSE score.8.There was no significant difference in perioperative anxiety level between the two groups,P>0.05.9.The incidences of adverse events such as bradykinesia or hypotension/hypertension,postoperative infection in the operation center were similar between the two groups,and there was no significant difference,P>0.05.10.During the 90-day follow-up period after surgery,no patient died in either group.There was no significant difference in hospitalization time between the two groups,P>0.05.11.By using the EQ-5D questionnaire to evaluate the quality of life of the two groups of patients,the results show that there is no statistically significant difference between the two groups of patients,P>0.05.Three months after operation,there was no significant difference in sleep quality between the two groups,P>0.05.Conclusion:1.The levels of serological nerve injury markers S100βand NSE were significantly increased in elderly patients with lower extremity tourniquet surgery during the perioperative period,inflammatory reactions occurred,and the incidence of POD was higher.2.RIPC+RIPostC can reduce the levels of serological nerve injury markers S100βand NSE in elderly patients with lower extremity tourniquet surgery,and lower the incidence of POD.The mechanism is related to the inhibition of inflammatory response.