Effect Of Ulinastatin On Postoperative Cognitive Function In The Elderly With Fracture

Objective: Postoperative cognitive dysfunction(POCD) is a frequent complication after surgery, characterized by impairment of memory and concentration detected by neuropsychological testing. It is associated with several complications including prolonged hospital stay, increased risk of permanent disability and higher mortality in the year following surgery. Studies have reported the incidence of POCD for noncardiac patients to range from 19% to 41%. The incidence of POCD is likely to increase due to the ageing population, with increasing morbidity and a higher rate of surgical procedures in elderly patients. POCD is postoperative common nervous system complications in the elderly, mainly manifested as mental disorders, anxiety, personality change and memory damaged. Hip fracture in the elderly is one of the common clinical diseases in orthopedics, and its most prominent feature is the elderly osteoporosis. In addition, the elderly with hip fracture is senile, and has poor health status and many comorbidities. The risk of anesthesia and operation was high when they expects treatment. Postoperative complication rate was significantly higher than that of young people. Surgical trauma can result in increased levels of inflammatory cytokines in the peripheral and central nervous system and thus impair cognitive function. Peripheral inflammatory cytokines can take effects on the central nervous system through both direct and indirect means. Cytokines can bind with their receptors in CNS and activatemicroglial cells, and also activate vascular endothelial cells. They induce neuro-inflammatory response and a series of effects of CNS. Surgical trauma can increase the level of inflammatory cytokines such as interleukin-1b, IL-6, tumour necrosis factor-a, and C-reactive protein in the peripheral and CNS and impair cognitive function.A substantial body of animal experiments indicating that elevated levels of proinflam-matory cytokines are closely associated with cognitive impairment supports this hypothesis. Ulinastatin has inhibitory effect on a variety of enzymes. It can inhibite the release of inflammatory mediators, and has a protective effect on the brain. Although ulinastin are thought to reduce the cognitive impairment after brain damage, but the relationship between ulinastatin and POCD has been assessed in only few studies. This study was to observe the incidence of POCD and influence of ulinastatin on postoperation cognitive function of elderly patients with hip fracture.Methods:Sixty patients over 65 year old patients with hip fracture were randomly divided into 2 groups: group ulinastatin(Group U) and group control(Group C). All patients underwent combined spinal-epidural anesthesia,and 0.25% bupivacaine 1.5~2.5ml were injected in subarachnoid,adjusting the level of anesthesia under T10. The patients in Group U received intravenous injections of ulinastatin with each dose of 25 00U/kg before skin incision and at the end of operation.At the same time point, the patients in group C received intravenous injection of saline.Cognitive function was assessed by Mini-Mental State Examination(MMSE)at the day of the operation(T0), 1(T1), 3(T2)and7(T3) day after opreation. The incidence of POCD was calculated. Blood samples were taken at T0 and T2 for determination of CRP.Results:1 There were no statistically significant differences between two groups of general data(P>0.05).2 The incidence of POCD at the first postoperative day was 20%, and the incidence of POCD in the first week after operation was 6% in all patients of both groups. The respectively incidence of POCD of Group U and Group C were 4.8% and 40.7%, Group U were significantly lower than Group C(P<0.05).3 There was no difference at T0(P>0.05). In Group U at T1, T2 MMSE scores(26.1±2.9, 26.5±2.6)were significantly higher than that in Group C(24.0±4.2, 24.5±3.7, P<0.05).4 Serum CRP in Group U(56.71±29.60)at T2 was lower than Group C(122.54±37.01, P<0.05).Conclusion:The incidence of POCD in all patients with hip fracture at the first day after surgery reached at 20%, but decreased at 6% at the seventh day. Ulinastatin could markedly reduce the incidence of POCD, it might be related to the reduction of systemic inflammatory response. Therefore inhibition of inflammatory response can prevent POCD.