Factors And Mechanism Of Neuropsychiatric Disorders In Elderly Patients After Operation

BackgroundNo mental disorder can occur after the surgery before now known elderly patients affected by a variety of factors anesthesia and surgical results in reversible brain dysfunction and volatility of postoperative acute mental disorder syndrome called postoperative cognitive dysfunction (postoperative cognitive dysfunction, POCD), the performance of mental disorder, anxiety, impaired memory, changes in personality and social integration such as the ability to change, severe dementia. Previous study showed that the likelihood of occurrence of POCD is10%～50%among senior patients with cardiac surgery and25.8%among senior patients within7days after non-cardiac surgery. POCD can occur among patients aged over70with a possibility of14%3months after operation. The morbidity and mortality rate of POCD can increase if it is not diagnosed and treated in time.The etiology and pathogenesis of POCD is still unclear, with the preoperative, intraoperative, and surgery-related factors.Now that POCD in elderly patients is the basis for the degradation of the central nervous system, induced by the surgery and anesthesia, due to the combined effects of multiple factors nerve dysfunction, disorders related to the central nervous system, endocrine and immune system. This study investigated the clinical point of early warning indicators of POCD, drug intervention, and a retrospective analysis of risk factors related to summarize, another from basic research to further explore the pathogenesis of POCD, and lay the foundation for early clinical prevention.Part I Clinical Studies1. Early predictors of acute postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgeryObjective To investigate the early predictors of acute postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery. Methods Sixty-six ASA I or II patients,aged65～85yr, scheduled for elective hip fracture surgery under epidural combined spinal anesthesia. After puncture into subarachnoid space,2ml CSF was drawed and stored in-70℃.Before anesthesia, after1,3,7days, blood was collected. Aβ1-40and HMGB1content of CSF and plasma was measured by ELISA. The expression of APP,HMGB1and IL-1βmRNA were detected by FQ-PCR. Before operation and postoperative day7, neurocognitive function test were performed. Results The incidence of POCD was24.2%(16/66) in postoperative day7. There were no satistically difference in content of Aβ1-40and HMGB1in CSF between group POCD and NPOCD(P＞0.05). Compared with preopration, the plasma HMGB1contents in postoperative day1,3,7were higher in group POCD, but the plasma Aβ1-40content was lower in postoperative day3,7, the expression of APP,HMGB1and IL-1βmRNA were evidently higher (P＜0.05). The plasma Aβ1-40content in group POCD was lower than those in group NPOCD in postoperative day3,7(P＜0.05). Conclusion The increase of plasma HMGB1contents and decrease of plasma Aβ1-40content predicted the incidence of POCD in elderly patients undergoing hip fracture surgery during epidural combined spinal anesthesia. 2. Risk factors of post-operative delirium and cognitive dysfunction in elderly patients undergoing hip joint replacement surgeryObjective To determine the risk factors for post-operative delirium (POD)and post-operative cognitive dysfunction (POCD)in elderly patients undergoing hip joint replacement surgery. Methods We selected200elderly patients under epidural anesthesia and scheduled for hip joint replacement surgery from May2010to August2012in Qingdao Municipal Hospital. POD was assessed by CAM at2days after operation.Cognitive function was assessed by MMSE at7days after operation. The factor was analyzed using multi-factor logistic regression to select risk factor for incidence of POD and POCD. Results Thirty-one patients developed POD (15.5%).Fifty-six patients developed POCD (28.0%).The results of multivariate logistic analysis showed that risk factors for postoperative delirium are the age＞75years old, injury time＞15h,education＜9years、preoperative depression, diabetes, intraoperative hypotension and risk factors for postoperative cognitivedys function are the age>80years old, injury time＞15h, intraoperative hypotension, preoperative depression, alcohol comsumption per week>5U, education＞12years,diabetes,VAS score4.(P＜0.05).ConclusionAge,injurytime,preoperative depression,diabetes,education and intraoperative hypotension is common risk factors of postoperative delirium and postoperative cognitive dysfunction. 3. Effects of parecoxib sodium analgesia on serum NSE and S-100β concentrations and postoperative cognitive function of the elderly patients undergoing acute replacement of femoral head.Objective To investigate the effects of parecoxib sodium analgesia on serum NSE and S-100βconcentrations and postoperative cognitive function of the elderly patients undergoing acute replacement of femoral head. Methods After IRB approval and informed consent, Eighty patients of both sexes, older than70years, American Society of Anesthesiologists physical status2-3,undergoing acute replacement of femoral head, combined spinal and epidural anesthesia and midazolam sedation,in Qingdao Municipal Hospital and Qingdao Hiser Medical Center, from January2011to May2012, were randomly assigned to control group (group C,n=40) and parecoxib group (group P,n=40). In group P, parecoxib sodium20mg or40mg(based on weight50kg) diluted with2ml saline was given by intravenous injection after admission with12hours intervals for six times. In group C, morphine2mg or4mg(based on weight50kg) was given at the first time. Additional morphine2mg was given to keep the pain visual analog scale (VAS) of3points or less in both groups. Primary observation indexes:(1)the postoperative time, additional amount of morphine;(2)the rate of postoperative delirium(POD) and postoperative cognitive dysfunction(POCD) at3days,1week,3months and6months after surgery(T1-T4);(3) serum level of NSE and S-100βwas measured at the time before analgesia (t0), before anesthesia(t1),the end of surgery(t2) and6hours,24hours,48hours after the surgery (t3-t5);(4)the other serious complications. Results Compared with group C, the additional amount of morphine,postoperative time, the rate of POD and POCD at T1-T4, the level of NSE was lower at t2-t5and the level of S-100βwas lower at tl-t5in group P(P＜0.05).No other serious complications were observed. Conclusion Parecoxib sodium analgesia can reduce the rate of POD and POCD in the elderly patients with neuroprotective effects. Part II Experimental Studies1.The expression of adenosine monophosphate activated kinase at hippocampus in postoperative cognitive dysfunction after splenectomy in aged rats. Objective To investigate the expression of adenosine monophosphate activated kinase(AMPK) at hippocampus in postoperative cognitive dysfunction (POCD) in aged rats. Methods Sixty-three male aged Sprague-Dawley rat, weighting480-550g, were randomly divided into3groups(n=21each):control group(group C),anesthesia group(group A),surgery group(group S). Spatial learning and memory were evaluated in the Morris Water Maze(MWM) both before treatment and posttreatment. In anesthesia group,10%chloral hydrate was injected in abdominal cavity. In the surgery group, the splenectomy surgery was proceed after the same anesthesia as group A. The equal volume of saline was given in group C. Then these groups were tested in WMW on1,3,7days. The rats, after the test, were divided into group POCD and NPOCD according to their performance in the test. Then the rats were sacrificed and had their hippocampuses removed. Western-blot was used to detect the protein of AMPK and P-AMPK. Results Compared with group C,the level of AMPK was higher in group S at1,3and7d(P<0.05), P-AMPK was higher at1d and3d (P＜0.05).The expression of AMPK was higher in group POCD(P＜0.05). Conclusion The cognitive function was changed ephemeral and the level of AMPK and P-AMPK were higher simultaneously in hippocampus in aged rats after splenectomy. The increased expression of AMPK and P-AMPK were related to POCD. 2. Effect of surgical trauma on expression of adenosine monophosphate activated kinase and activation of astrocyte in hippocampus in aged ratsObjective To explore the effect of surgical trauma on expression of mRNA of adenosine monophosphate activated kinase and activation of astrocyte in hippocampus in aged rats.Methods Seventy rats aged18months were randomly divided into two groups:Groups S (anesthesia and splenectomy) and Groups C (anesthesia).Both of the groups were divided into5subgroup according to observation time(1day before operation or anesthesia,1、3、5and7day after operation or anesthesia),i.e.SO, S1, S3, S5, S7and CO, Cl, C3, C5, C7. Morris water maze test was used to observe cognition at1day before anesthesia or operation, days1,3,5and7after anesthesia or operation; rt-PCR was used to determine the expression of AMPK-α; Immunohistochemisty was used to determine the expression of GFAP in the astrocyte in hippocampus field. Results Compared to S0,the escape latency and the total distance was significantly extended on S1and S3(P＜0.05); AMPK-α was significantly increased on S1, S3and S5, furthermore, there were two peak on S1and S5(P＜0.05); The expression of GFAP in astrocyte was significatively increased on S1and S3(P＜0.05). Conclusion Cognitive function was decreased after splenectomy,while the increasion of AMPK in the astrocyte in hippocampus filed was significatively increased and the expression of GFAP in astrocyte was significatively increased...