乌司他丁对老年患者髋关节置换术后谵妄的影响

Application of ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty

目的 观察围术期应用乌司他丁对老年患者行髋关节置换术术后谵妄的影响。方法选取择期髋关节置换术老年患者120例,美国麻醉医师协会(ASA)分级Ⅰ~Ⅱ级,年龄在65~90岁,无神经、精神系统疾病,无长期服用镇静、抗抑郁药,术前沟通、依从性好;能配合完成术后随访。应用随机数字表法分成4组:乌司他丁组(U 1、U 2、U 3组)和对照组(C组),每组30例,术中应用静吸复合全麻。手术切皮前分别予U 1组2 500 U/kg、U 2组5 000 U/kg、U 3组10 000 U/kg乌司他丁静脉维持1 h,术后第1、2天再继续静滴等量乌司他丁,C组等时静滴生理盐水。记录4组意识恢复时间、意识恢复后视觉模拟量表(VAS)评分、术后改良的警觉/镇静(OAA/S)评分和拔管后躁动评分;术后谵妄评定方法(CAM)评分;术后谵妄发生例数;记录术前和术后不同时点的白介素-6(IL-6)、S-100钙结合蛋白β亚单位(S-100β)和脑源性神经营养因子(BDNF)变化。一般情况、拔管时间及意识恢复质量评分采用单因素方差分析,CAM评分、IL-6、S-100β及BDNF数据采用重复测量资料方差分析,术后谵妄发生例数采用卡方检验进行统计学分析。结果 U 2组、U 3组较C组、U1组拔管后躁动评分低( F =34.41, P< 0.05 )、意识恢复时间短( F =8.45, P< 0.05)、术后改良OAA/S评分低( F =7.33, P<0.05 );术后3 d,乌司他丁组CAM评分均低于C组( F =8.61, P <0.05);术后C组出现谵妄例数多( 2 =8.76, P <0.05);术后6~24 h IL-6浓度U 1、U 2、U 3组低于C组( F =16.84, P <0.05);术后6~24 h的S-100β浓度 U 1、U 2、U 3组低于C组( F =7.613, P <0.05);术毕当时至术后12 h血清BDNF浓度U 1、U 2、U 3组明显高于C组( F =38.54, P <0.05)。结论髋关节置换术围术期使用5 000 U/kg与10 000 U/kg乌司他丁量,可缩短意识恢复时间,减低拔管后躁动的发生,减轻老年人髋关节置换术后谵妄的发生;可能与乌司他丁影响炎症因子IL-6,从而减少S-100β和保持BDNF浓度有关。

Objective To explore the effect of perioperative ulinastatin on postoperative delirium in elderly patients undergoing hip arthroplasty.Methods A total of 120 elderly patients undergoing elective hip arthroplasty were recruited in the study,aged 65 to 90 years old,American Society of Anesthesiologists (ASA) I to II,without neurological or psychiatric diseases,no history of sedative or antidepressant drugs;with good communication and postoperative follow-up.The random number table method was divided into four groups:ulinastatin groups (group U 1,U 2,U 3) and control group (group C),30 cases in each group,and the patients were used by Intraoperative intravenous inhalation combined with general anesthesia.Before the operation,the patients were given 2 500 U/kg ulinastatin in group U 1,5 000 U/kg in group U2,10 000 U/kg in group U 3 for 1 h,and continued intravenous infusion the same doses of ulinastatin on the first and second day after the operation.Group C received saline intravenously at the same time.The information including the time of consciousness recovery,visual analogue scale (VAS),the improved observer s assessment of alertness/sedation scale (OAA/S) and the confusion assessment method (CAM) score after operation,the number of delirium cases after operation,and the changes o interleukin-6 (IL-6)f,S-100 calcium binding protein beta subunit (S-100β) and brain-derived neurotrophic factor (BDNF)at different time points before and after the operation,were recorded.General condition,extubation time and consciousness recovery quality score data were analyzed by one-way analysis of variance.The CAM score,IL-6,S-100β and BDNF data were analyzed by repeated measures data analysis.The number of postoperative delirium cases was calculated by chi-square test.Results After extubation,the agitation scores in U 2 group and the U 3 group were lower than the group C and U 1( F =34.41,P<0.05),the recovery time of consciousness was shorter( F =8.45,P= 0.008),and the postoperative modified OAA/S scale were lower( F =7.33,P<0.05).Three days after surgery,CAM score of ulinastatin groups were higher than group C ( F =8.61,P<0.05);there were more cases of delirium in group C after the operation( 2 =8.76,P<0.05).After 6 h to 24 h,IL-6 concentration in group U 1,U 2,and U 3 were significantly lower than group C ( F =16.84,P<0.05),S-100β group U 1,U 2,and U 3 were lower than group C ( F =7.613,P<0.05).After surgery to 12h,serum BDNF concentration in group U 1,U 2,and U 3 were significantly higher than that in group C ( F =38.54,P<0.05).Conclusions The use of 5,000 U/kg and 10 000 U/kg ulinastatin in the perioperative period of hip arthroplasty can shorten the recovery time of consciousness and reduce the occurrence of agitation after extubation.It may be that the application of ulinastatin affects inflammation.Factor IL-6,which reduces S-100β and maintains BDNF concentration,is associated with the reduction of spasticity after hip arthroplasty in the elderly.