Effects Of Ulinastatin On Post-operative Cognitive Dysfunction In Elderly Patients With Lower Limb Joint Replacement Surgery

Objective: Post-operative cognitive dysfunction seriously influences the life qualityafter surgery in elderly patients, perioperative stress reaction and inflammation due tofactors such as operation trauma, bleeding and blood transfusion is closely related with theoccurrence of POCD. Ulinastatin is organ-protecting in a variety of diseases throughprotease inhibiting and anti-inflammation effects. Ulinastatin effectively inhibits stressreaction during operation and inflammatory caused by operation injury. This studyselected elderly patients undergoing lower limb joint replacement surgery, to observe theeffect of ulinastatin in reducing the incidence of POCD, then explore its protectivemechanism.Method:60elderly patients were selected, who hospitalize in the Department oforthopedics of Xijing Hospital and accept lower limb joint replacement operation during2010August to2012August, According to the computer random number table and paireddesign by sex and age, patients were divided into two groups: Ulinastatin group（UTIgroup）and Control group（CON group）. Patients in UTI group were treated withulinastatin200000U, which dissolved in100ml normal saline, then infused in30minutesrespectively at the beginning of the operation and6h after operation; Patients in CON group were treated with ulinastatin100ml saline respectively at the beginning of theoperation and6h after operation.After patients entring the operation room, they were monitoring of non-invasivearterial pressure (BP), heart rate (HR), electrocardiogram (ECG), pulse oxygensaturation (SPO2), then opened the upper limb vein to infusion. Induct patients withmidazolam, propofol1-1.5mg1-1.5mg/kg, fentanyl, vecuronium0.04ug/kg0.1mg/kgfollowed by intravenou, after successful intubation, setting a tidal volume of8~10ml/kg,respiration rate10/min, inhalation of100%oxygen, flow rate is1L/min, maintainanesthesia with1-1.5MAC of isoflurane, continuous pump infusion of remifentanil,intermittently give vecuronium0.03mg/kg on-demand.General data of patients such asage, gender, height and weight were recorded, and blood pressure, heart rate,electrocardiogram and pulse oxygen saturation during operation were continuouslymonitored; anesthesia time, operation time, anesthesia drug dosage, amount of bleeding,hospitalization time and postoperative adverse reaction were also recorded.4ml venous blood was collected when preoperative、the end of operation and24hours postoperative respectively, then stored in a dry test tubes,4℃for half an hour aftercentrifugation (3000rm,15minutes), the serum was transfered to-80℃refrigerator frozenfor detecting the content of IL-1β, IL-8, TNF-α, S100B and NSE. On deferent time points:immediate postoperative (T0),15min after operation (T15),40min after operation(T40),1days after operation (D1),3days after operation (D3),7days after operation(D7) and1months after operation (M1), we applicate of postoperative recovery qualityscale (Post-operative Quality Recovery Scale, PQRS) by evaluating patients inphysiological, bad feelings, emotions, daily function, cognitive function and daily lifeability recovery6aspects. On deferent time points: postoperative day7(D7) andpostoperative1months (M1) assess the cognitive function by Mini-Mental StateExamination (Mini-Mental State Examination, MMSE), score decreased more than1standard deviation and cognitive function decline, diagnosed as POCD, and comparedwith the results of PQRS scale.Using SPSS16.0statistical software for analysis, measurement data with the mean±standard deviation(±s), compared with single factor analysis of variance(One-Way ANOVA), such as stratification within group comparison, using double factoranalysis of variance (Two-Way ANOVA). Count data using chi-square test, P<0.05implicates the difference was statistically significant.Results: The preoperative conditions including age, education, body weight, ASAscore, smoking and drinking in two groups of patients had no significant difference(P>0.05). The operation and anesthesia conditions in two groups of patients showed nosignificant difference (P>0.05).The PQRS score values of UTI group were higher than those in CON group,atpostoperative15min,40min,1d after operation,3ds after operation, and7ds afteroperation five time points, two groups have statistically significant difference (P<0.05);and1m after operation, PQRS scores of the two groups have no significant differences(P>0.05); MMSE score of UTI group were higher than those in CON group on the7daysafter operation and1m after operation, two groups have statistically significant difference(P<0.05);7ds after operation and1m after operation, the incidence of POCD between UTIgroup (20%,16%) and CON group (30.4%,26.1%) had no significant difference(P>0.05).The IL-1β content of UTI group patients at24h after operation, was significantlylower than that of CON group (P<0.05), there was no significant difference in serum IL-1βcontent of two groups of patients before and after operation (P>0.05); at24h afteroperation, the content of serum IL-8in UTI group were significantly higher than those ingroup CON (P<0.05), no significant difference in0h between the two groups of patientsthe serum IL-1β content before and after operation (P>0.05); preoperative,0h afteroperation and24h after operation serum TNF-α content in patients of two groups had nosignificant difference (P>0.05). Preoperative,0h after operation and24h after operationserum S100β and NSE content in patients of two groups were not significantly different(P>0.05). Conclusion: Ulinastatin can significantly improve the postoperative MMSE score andPQRS score, and effectively improve the postoperative cognitive function; the effect isachieved possibly through inhibiting the inflammatory reaction, reducing the content ofIL-1β and increasing the secretion of IL-8.