| Backgrounds and Objective:Postoperative cognitive dysfunction (POCD) is a common complication after operation and anaesthesia, including the change of cognitive function such as orientation, thinking, memory, attention, et al. Mild symptoms could self-heal. Serious symptoms, for example, loss of judgment and language generalization, personality changes, the most serious dementia, will lead to lower or loss of social activities, work and self-care ability, a serious decline in quality of life, serous burden on society.Although the etiology and pathogenesis of POCD were not very clear, it has been shown that old age is one of the main risk factors. Currently considered that on the basis of neurodegeneration, POCD in elderly is neurological dysfunction with a variety of factors:general information of patients preoperatively, anaesthesia, narcotic, surgery type, descendiblity and related factors such as hypotension, hypoxia, hyperventilation, etc. One of the pathogenesis is activation of the immune system inflammatory response caused by various stress stimuli. Surgery, as a traumatic treatment, can produce excessive inflammatory cytokines through the activation of immune system.Parecoxib sodium is elective cyclooxygenase (COX-2 inhibitor). Studies have shown that COX-2 inhibitor can lead to decreased production of prostaglandin and oxygen free radicals, and play a role in brain protection by changing metabolic pathway of arachidonic acid. So, is parecoxib sodium having protection on postoperative cognitive decline?Through the application of parecoxib sodium with the concentration of inflammatory cytokines and assessment of cognitive function preoperatively and postoperatively; this study is to observe if parecoxib sodium can reduce the incidence of POCD and the release of inflammatory cytokines in elderly undergoing joint replacement.Methods:Forty-two ASAⅠ-Ⅱpatients over 65 yr undergoing elective knee or hip replacement under general anaesthesia were studied. Patients with significant heart, lung, liver, renal and neuromuscular diseases were excluded. None of them had taken preoperative drugs which can affect neuromuscular transmission function.The patients were randomly divided into two groups:Parecoxib (P=20) and control(C=22) group. Patients in group P received intravenous Parecoxib 40 mg 15min before induction of anaesthesia and 12h after the first application. In group C, normal saline was given instead of parecoxib in the same volume and at the same speed.All the patients did not use premedications, routinely monitored electrocardiogram, heart rate, blood pressure and pulse oxygen saturation (SpO2), and establishmented right internal jugular vein catheterization access under local anaesthesia. Anaesthesia induction was performed with intravenous midazolam 0.04-0.05 mg/kg, fentanyl 3-5μg/kg, etomidate 0.2-0.3mg/kg and rocuronium 0.6mg/kg. When muscle relatents achieve maximum inhibating effects, the patients were intubated and mechanically ventilated. Continuous anaesthesia was performed with propofol 4-6mg/kg/h and remifentanil 0.1-0.2ug/kg/min,and adjust micro-pump injection rate according to intraoperative hemodynamic changes. The blood pressure should be maintained between up and down of 20% of baseline intraoperatively. All the patients were given intravenous azasetron 10mg and sufentanil 0.1 mg/kg 15-20min before the end of operation.Patient-controlled intravenous analgesia (PCIA) with sufentanil was administered with background infusion of 2ml/h, bolus injection of 0.5ml and lock-out time of 15min.Vital signs were recorded and venous blood samples were collected immediately before induction of anaesthesia (T1),4h after operation (T2),24h postoperatively (T3) and 48h postoperatively (T4). The plasma levels of IL-6 and TNF-a were measured by enzyme-linked immunosorbent assay. A bottery of neuropsychological tests--Montreal Cognitive Assessment (MoCA)--performed and scored preoperatively and 7 days after operation. Statistics analysis:Statistical package(SPSS 16.0) was used for the data processing. The numerical data variables expressed as mean±standard deviation. Analyze different types of data with descriptive statistics, analysis of variance, t test,χ2 test and correlation analysis.Results:1. General information There were no significant difference on age, gender composition, height, weight, ASA classification,leval of education and complications among two groups (P>0.05). Time consumption of operation and recovery, bleeding, urine, fluid volume, blood transfusion have no significant difference (P>0.05).2. Condition during operation:No significant difference was noted regard to HR, MAP, EtCO2 and SpO2 (P>0.05). The amount of narcotic drugs have no significant difference (P>0.05)3. The levels of inflammatory cytokines:There were no significant difference of IL-6 levels at T1 between P and C group (P>0.05). The plasma levels of IL-6 in both groups were significantly higher at T2, T3 and T4 than that at T1 (P<0.01). But at T2, T3 and T4, plasma IL-6 level was lower in group P than that in group C (P<0.01). There were no difference of the plasma level of TNF-a in two groups (P>0.05). The plasma level of TNF-a was significantly higher in group C than group P at T3 (P<0.05).4. Montreal Cognitive Assessment (MoCA)In the test of Delayed Recall, the scores of group C were significantly decreased compared with group P (P<0.05). There was almost no change in group P (P>0.05).5. The incidence of POCD6 patients in group P developed POCD and the incidence was 30.00%.8 patients in group CX developed POCD and the rate was 36.36%. Although the incidence of group P is less than group C, there is no statistically significant difference (P>0.05).6. The correlation between the levels of inflammatory cytokines and POCDNegative correlation was found between the elevations of IL-6 levels 24h after operation and the low score of Delayed Recall 7 days postoperatively.Conclusion:1. Parecoxib Sodium can reduce the release of inflammatory cytokines (IL-6, TNF-a), inhibition inflammation in elderly undergoing knee or hip replacement.2. Negative correlation was found between the elevation of IL-6 levels and the decline of certain memory function.3. Although parecoxib Sodium can improve certain memory function postoperatively, it can not decrease the general incidence of POCD 7 days after knee or hip replacement in elderly. |
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