| Objective:To evaluate the impact of intravenous injection of ulinastatin against early cognitive impairment and explore the correlation mechanism in the process.Methods:The study included 46 elderly patients scheduled for a hip replacement surgery from October 2015 to January 2016 (age:70-85; ASA:Ⅱ-Ⅲ). Patients were randomly divided into two treatment groups:Control (group C, n= 23) and Ulinastatin (group U, n= 23). Electrocardiogram, heart rate, pulse oximetry, noninvasive blood pressure and hemoglobin oxygen saturation (SpO2) were continuously monitored during surgery and oxygen was given for all patients through the mask (4L/min) before surgery. Before anesthesia, the ulinastatin group received ulinastatin as bolus of 5000U/kg over 10minutes, followed by the other bolus of the same dosage at the end of the surgery; the control group received the saline. All patients were anesthetized using spinal-epidural anesthesia, as follows. The patients were placed in the lateral decubitus position. The epidural space was identified at the L3-L4 level. After free flow of the cerebral spinal fluid was obtained,2.5ml of 0.5% ropivacaine solution was injected within 30s.2% lidocaine was injected according to the requirement of the surgery during the operation.We examined the effect of ulinastatin treatment on the improvement of cognitive function using the Mini-Mental State Examination (MMSE) at preoperation and 3 d postoperation. Besides, blood samples(5ml) were collected and centrifuged before inducing anesthesia (TO), at the end of surgery (T1) and three days after the end of surgery (T3). The serum fraction was removed and stored at -80℃. The serum samples were used to observe changes in the levels of IL-6, IL-10, MDA, S100β and brain derived neurotrophic factor (BDNF)Results:1.There were no significant difference in gender, age, body weight, ASA classification, operation time between groups (P> 0.05) and the MMSE scores did not differ between groups at preoperation (P> 0.05)2. The ulinastatin group had a lower incidence of postoperative cognitive impairment than the control group in T3(30.43% versus 4.35%, P< 0.05)3. In the control group, serum IL-6 concentration increased at T1 and T3 (P< 0.05). However, the ulinastatin group had lower serum IL-6 concentration than that in the control group (P< 0.05); serum IL-10 concentration increased at T1 and T3(P< 0.05), and there were no significant differences between groups in IL-10 concentration at three time points (P> 0.05).4. In the control group, serum MDA levels increased at T1 and T3 (P< 0.05). The ulinastatin group had lower serum MDA levels than those in the control group (P <0.05).5. Compared with the preoperative serum S100β, those at T1 were significantly increased in the control group. However, the levels in ulinastatin the group were markedly lower than those in the control group at T1.6 Compared with the preoperative serum BDNF, those those at T1 and T3 were significantly decreased in the control group. However, the BDNF levels in the ulinastatin group were markedly higher than those in the control group at T1 and T3 (P< 0.05).Conclusions:Ulinastatin treatment attenuated early cognitive impairment in elderly patients undergoing hip replacement surgery. Furthermore, serum IL-6.IL-10, S100β, MDA and BDNF were involved in the mechanism underlying the therapeutic effect of ulinastatin on cognitive function. Therefore, our results indicated that ulinastatin may be considered as an effective neuroprotective agent for the prevention and treatment of early postoperative cognitive impairment. |
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