安宫牛黄丸辅助氟哌啶醇治疗重症患者术后谵妄的临床研究

Clinical research on Angongniuhuang pill adjuvant to haloperidoi for the treatment of intensive care unit patients with postoperative delirium

目的 观察安宫牛黄丸辅助氟哌啶醇治疗重症患者术后谵妄的临床疗效及其安全性。方法 前瞻性研究新疆医科大学第一附属医院重症医学科（ICU）术后患者（2013年1月至2014年12月），使用重症医学意识模糊评估法，共收集谵妄患者243例，通过计算机随机分组软件（SAS 9.1）将纳入研究的受试者随机分为安宫牛黄丸辅助氟哌啶醇治疗（A）组、单纯氟哌啶醇治疗（F）组。两组干预措施终点均为重症医学意识模糊评估法评分连续两次阴性或最多达7 d治疗。分别记录两组患者的一般资料、有效性指标及安全性指标，通过SPSS 19.0统计软件分析两组各指标间的关系。计量资料用均数±标准差（x±s）描述；组间比较采用成组t检验；重复测量采用方差分析。计数资料用例数、构成比描述；组间比较采用χ2检验，以P＜0.05为差异具有统计学意义。结果 两组患者一般资料比较差异无统计学意义，而有效性指标中谵妄持续时间、ICU治疗时间A组较F组缩短，且差异有统计学意义[（3.0±0.9）d vs.（3.8±1.0）d，P=0.010；（6.2±1.4）d vs.（6.7±1.5）d，P=0.008]。在谵妄确诊时（T0），所有患者都存在脑电图异常情况，随着治疗的进行，脑电图异常率逐渐下降，治疗后第1天（T1）时A组、F组差异无统计学意义（95.7 % vs.97.5 %，P=0.045）,治疗后第2天（T2）及第3天（T3）时A组、F组差异有统计学意义（65.5 % vs.77.7 %，P=0.038；42.2 % vs.56.2 %，P=0.032）。两组S100β蛋白、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）水平T0时均有升高组间差异无统计学意义，在T1、T2、T3时均成下降趋势，且A组较F组下降快，差异有统计学意义（S100β：时间效应P〈 0.01，组间效应P=0.002，交互效应P=0.686；IL-6：时间效应P〈 0.01，组间效应P=0.034，交互效应P=0.01；TNF-α：时间效应P〈 0.01，组间效应P=0.003，交互效应P=0.516）。安全性指标好转出院率A组高于F组（89.7 % vs.79.3 %，P=0.029），术后合并症发生率、术后28 d病死率A组低于F组（45.7 % vs.58.7 %，P=0.045；12.9 % vs.24.0 %，P=0.028）。结论 安宫牛黄丸辅助氟哌啶醇治疗谵妄从安全性有效性方面均较单独使用氟哌啶醇好，可能成为中西药结合治疗谵妄的新方法。

Objective To observe the clinical effects and safety of Angongniuhuang Pill （a traditional Chinese medical preparation） adjuvant to （ICU） patients in postoperative delirium. Methods haloperidol for the treatment of Intensive Care Unit A prospective study of 243 postoperative patients withdelirium adimitted in Intensive Care Unit of Xinjiang Medical University First Affiliated Hospital （January 2013-December 2014） , by using confusion assessment method of Intensive Care Unit （CAMICU）. All of 243 patients with delirium were randomly divided into two groups by computer randomization software （SAS 9.1 ） ： group A in which patients were treated with Angongniuhuang Pill adjuvant to haloperidol and group Fin which patiets were treated with haloperidol alone. The end of two intervention methods was determined by two consecutive CAMICU showing negative or the treatment were ended up at seven days treatment. The data of general information, and the results of treatment were recorded and analized by statistical software SPSS 19. 0. The measurement data was expressed as mean ＋ standard deviation; the comparision between two groups was tested by t test; and repeated measurement was analised by variance. Count data was described as number and constitution ratio; and intergroup comparision was tested by Chi-square test. Results There was no significant difference in general information between two groups. The delirium duration and ICU treatment time in group A were shorter than those in group F [ （3.0 ±0. 9） d vs. （3.8 ± 1.0） d, P= 0.010; （6.2 ± 1.4） dvs. （6.7 ±1.5） d, P= 0.008]. When delirium was diagnosed （TO）, all patients had EEG abnormalities. As treatment went on, EEG abnormal rate gradually declined. At day one （T1）, there was no statistically significant difference in EEG findings between group A and group F （95.7% vs. 97.5%, P = 0.045）. At day two （T2） and day three （T3）, there was statistically significant difference in EEG findings between group A and group F （65.5% vs. 77.7%, P = 0. 038 ; 42. 2% vs. 56. 2% , P = O. 032）. The levels of S10013 protein, interleukin-6 （ IL-6 ） , tumor necrosis factor α （TNF-α） in two groups at TO were all elevated without noticeable difference. These markers were all deceased at T1, T2, T3, but the speed of descend in group A was relatively faster than that in group F. The differences were statistically significant （S10015： time effect P 〈 0. 01, inter-group effectp = 0. 002, interaction effectp = 0. 686 ; IL-6 ： time effect P 〈 0. 01, inter-group effectp = 0. 034, interaction effectp =0. 01 ; TNF-α： time effect P 〈 0.01, inter-group effectp = 0. 003, interaction effectp = 0. 516） . The discharge rate in group A after improvement of general condition was higher than that in group F （89. 7% vs. 79.3%, P= 0.029） . The incidence of postoperative complications and mortality 28 days after operation in group A were lower than those in group F （45.7% vs. 58.7% P = 0. 045; 12. 9% vs. 24.0%, P = 0. 028） . Conclusion During the treatment of delirium, Angongniuhuang pill adjuvant to haloperidol was a better method compared with using haloperidol alone in respect of effectiveness and safety perspectives. It may be a novel approach to the treatment for delirium by the combination of Chinese and Western medicine.