不同剂量氟比洛芬酯对老年全髋关节置换术患者术后神经认知功能的影响

Effects of different doses of flurbiprofen on neurocognitive function in elderly patients undergoing total hip arthroplasty

目的评价不同剂量氟比洛芬酯对老年全髋关节置换术患者术后神经认知功能的影响。方法择期全身麻醉下行全髋关节置换术的患者120例,男61例,女59例,年龄65~75岁,BMI 19~28 kg/m^2,ASAⅡ或Ⅲ级,采用随机数字表法分为四组:氟比洛芬酯0.5 mg/kg组(F1组)、氟比洛芬酯1.0 mg/kg组(F2组)、氟比洛芬酯1.5 mg/kg组(F3组)和空白对照组(C组),每组30例。术前30 min分别给予氟比洛芬酯0.5 mg/kg(F1组)、1.0 mg/kg(F2组)和1.5 mg/kg(F3组),C组不予处理。分别采集术前1 d、术后1、3、5和7 d中心静脉血样,采用ELISA法测定血清中IL-6和趋化因子CXC配体13(CXCL13)浓度,并于同时点采用简易智能状态检查量表(MMSE)对患者的认知功能进行评定。记录术后1、6、24和48 h VAS评分和术中及术后舒芬太尼用量,记录消化道出血、恶心呕吐、皮肤瘙痒等氟比洛芬酯相关不良反应发生情况。结果与术前1 d比较,四组术后1、3、5和7 d时IL-6、CXCL13浓度明显升高(P<0.05),术后不同时点F1组、F2组和F3组IL-6、CXCL13浓度明显低于C组(P<0.05),F2组和F3组明显低于F1组(P<0.05)。与术前1 d比较,四组术后1、3、5和7 d MMSE评分明显降低(P<0.05),术后不同时点F1组、F2组、F3组MMSE评分明显高于C组(P<0.05),F2组和F3组明显高于F1组(P<0.05)。与C组比较,F2组和F3组PND发生率明显降低(P<0.05)。术后不同时点F1组、F2组和F3组VAS评分和舒芬太尼用量明显低于C组(P<0.05),F2组和F3组明显低于F1组(P<0.05),F3组明显低于F2组(P<0.05)。四组无一例消化道出血、恶心呕吐、皮肤瘙痒等术后氟比洛芬酯相关不良反应发生。结论 1.0 mg/kg或1.5 mg/kg氟比洛芬酯均可明显降低老年全髋关节置换术患者术后神经认知障碍的发生率,其机制与降低炎性因子IL-6和趋化因子CXCL13浓度有关。1.5 mg/kg氟比洛芬酯可提供更好的术后镇痛效果。

Objective To evaluate the effects of different doses of flurbiprofen on neurocognitive function in elderly patients undergoing total hip arthroplasty. Methods A total of 120 patients scheduled for total hip arthroplasty, 61 males and 59 females, aged 65-75 years, with BMI 19-28 kg/m^2, falling into ASA physical status Ⅱ or Ⅲ,were randomly assigned into four groups(n = 30): flurbiprofen 0.5 mg/kg group(group F1), flurbiprofen 1.0 mg/kg group(group F2), flurbiprofen 1.5 mg/kg group(group F3) and the control group(group C). Flurbiprofen was seperately given 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg in group F1, group F2 and group F3 30 min before operation, the group C with no flurbiprofen. Central venous blood samples were reserved respectively 1 d before surgery, 1, 3, 5 and 7 d after surgery, and the concentrations of IL-6 and chemokine CXC ligand 13(CXCL13) in serum were determined by ELISA. At the same time, MMSE was used to evaluate the patients’ cognitive function.The VAS score at 1, 6, 24, and 48 h after surgery and sufentanil dosage were recorded. Flurbiprofen related adverse effects(gastrointestinal bleeding, nausea, vomiting, and pruritus) were recorded. Results Compared with that 1 d before surgery, the concentrations of IL-6 and CXCL13 in the four groups increased significantly at 1, 3, 5 and 7 d after surgery(P<0.05), compared with that in group C, the concentrations of IL-6 and CXCL13 were decreased in group F1, group F2 and group F3(P<0.05), compared with that in group F1, the concentrations of IL-6 and CXCL13 were decreased in group F2 and group F3(P<0.05). Compared with that 1 d before surgery, the MMSE scores in the four groups decreased significantly at 1, 3, 5 and 7 days after surgery(P<0.05), compared with that in group C, the MMSE scores were increased in group F1, group F2 and group F3(P<0.05), compared with group F1, the MMSE scores were increased in group F2 and group F3(P<0.05). Compared with group C, the incidence of neurocognitive disorderswere decreased in group F2 and group F3(P<0.05). Compared with that in group C, the VAS score and sufentanil dosage were significantly decreased in group F1, group F2 and group F3(P<0.05), Compared with that in group F1, the VAS score and sufentanil dosage were significantly decreased in group F2 and group F3(P<0.05). Compared with group F2, the VAS score and sufentanil dosage were significantly decreased in group F3(P<0.05). None of the patients in the four groups had gastrointestinal bleeding, nausea, vomiting, and pruritus. Conclusion 1.0 mg/kg and 1.5 mg/kg flurbiprofen can reduce the incidence of perioperative neurocognitive disorders in elderly patients undergoing total hip arthroplasty which may be related to the inhibition of the expression of the inflammatory factor IL-6 and the chemokine CXC ligand 13(CXCL13). Besides, 1.5 mg/kg flurbiprofen provides better postoperative analgesia.