厚朴排气合剂对开腹胃肠道手术后胃肠功能恢复影响的多中心前瞻性研究

Effects of Houpupaiqi mixture on recovery of gastrointestinal function after open gastrointestinal surgery ： a multi-center prospective study

目的评价中成药厚朴排气合剂对开腹胃肠道手术后患者胃肠功能恢复的有效性及安全性。方法采用多中心前瞻性随机双盲对照方法，分析2010年10月至2011年9月3家临床研究中心纳入开腹胃肠道手术患者144例（北京大学人民医院胃肠外科66例、首都医科大学附属北京友谊医院普通外科72例、广东省人民医院普通外科6例）的临床资料，根据Ⅲ期临床试验结果以2：1按随机数字表法将人组患者分为两组，试验组96例，对照组48例，入组后均接受治疗。其中5例患者因不符合本研究标准而剔除，共有139例患者纳入研究，其中试验组92例，对照组47例。本研究经各研究中心伦理委员会审核批准，患者签署知情同意书。两组患者于术后16h及20h分别经胃管给予厚朴排气合剂50ml（试验组）或厚朴排气合剂模拟剂50ml（对照组），术后进行常规外科治疗，待肛门排气后拔除胃管开始饮水，并逐步进食肠内营养液或流质饮食。两组患者采用统一的静脉镇痛方案。研究期间禁止使用增强或抑制胃肠动力药物。术后记录患者肠鸣音恢复时间、首次肛门排气时间、首次排便时间、首次进食固体食物时间。手术前、给药后每天记录患者生命体征。术后第6天进行血、尿常规，肝、肾功能，心电图检查，并记录药物不良事件。上述时间计算方法均为出现时间与手术结束时间的时间差值。采用Kaplan—Meier法，计算四分位数（Q1、Q2、Q3）手术后各指标出现时间及各时点出现率，并绘制Kaplan—Meier估计曲线，对两组患者的时间分布采用Log—rank检验。计量资料采用t检验或秩和检验，计数资料列出频数和百分数，采用X。检验或Fisher确切概率法。结果试验组和对照组患者术后中位肠鸣音恢复时间分别为21．4（20．0，23．7）h和47．5（44．0，56．5）h，中位首次肛门排气时间分别为45．0（40．0，54．0）h和91．0（87．0，93．8）h，中位术后首次排便时间分别为65．5（54．7，74．0）h和98．0（94．0，113．5）h，两组比较，差异有统计学意义（Log—rank值分别为21．67，53．15，11．81，P〈0．05）。试验组和对照组中位首次进食固体食物时间分别为72．5（66．2，110．5）h和116．3（114．8，117．3）h，但差异无统计学意义（Log—rank值为13．70，P〉0．05）。两组患者用药前后体温、呼吸、心率、收缩压、舒张压等生命体征的变化比较，差异元统计学意义（Z=0．03，0．68，0．97，0．22，0．72，P〉0．05）；用药后血、尿常规，肝、肾功能，心电图异常患者例数比较，差异无统计学意义（P〉0．05）。两组患者均无机械性肠梗阻和吻合口漏等严重药物不良事件发生。结论厚朴排气合剂可促进开腹胃肠道手术后患者胃肠功能恢复，临床使用安全、有效。

Objective To investigate the effects of Houpupaiqi mixture on the recovery of gastrointestinal function after open gastrointestinal surgery, and evaluate the efficacy and safety of Houpupaiqi mixture. Methods A total of 144 selected patients who underwent open gastrointestinal surgery were enrolled into the multi-center prospective randomized double-blind controlled clinical trial from October 2010 to September 2011. Of the 144 patients, 66 were from People＇s Hospital of Peking University, 72 were from Beijing Friendship Hospital of Capital University of Medical Sciences, and 6 were from People~ Hospital of Guangdong Province. All the patients were randomly divided into 2 groups （ test group ： 96 patients, control group ： 48 patients） at the ratio of 2 ： 1 according to the random number table. Five patients who did not meet the criteria were excluded from the study, and then there were 92 patients in the test group and 47 patients in the control group. The study was assessed by the ethics committees, and all the patients signed the informed consent form. Houpupaiqi mixture （50 ml） or placebo （50 ml） were administered in the test group and control group at postoperative 16 and 20 hours, respectively. Parenteral and enteral nutritional support were given after pulling out of gastric tube. A standard intravenous analgesia was applied in the 2 groups, and agents which stimulate or suppress gastrointestinal motility were prohibited. The time for the recovery of regular bowel sounds, the first exhaust and first defecation time, and the time of first solid food intake of the 2 groups were recorded. Vital signs were recored before operation and after drug administration. Blood and urinary routine test , hepatic and renal function test, electrocardiogram examination, record of adverse drug event were carried out at postoperative day 6. The time for the indexes above and relevant frequencies were calculated, and the survival curve were drawn by Kaplan-Meier method. All the time points were analyzed using the Log-rank test. The measurement data were analyzed using the t test or rank-sum test, and the enumeration data were analyzed using the chi-square test or Fisher exact probability. Results The median time for the recovery of regular bowel sounds, median time for first exhaust and defecation were 21.4 （20.0, 23.7）hours, 45.0 （40.0, 54.0） hours and 65.5 （54.7, 74.0） hours in the test group, and 47.5 （44.0, 56.5） hours, 91.0 （ 87.0, 93.8） hours, 98.0 （94.0, 113.5 ）hours in the control group, there were significant differences between the 2 groups （ Log-rank values =21.67, 53.15, 11.81, P 〈0.05）. The median time of first solid food intake were 72.5 （66.2, 110.5 ） hours of the test group and 116.3 （ 114.8, 117.3 ） hours of the control group, with no significant difference between the 2 groups （ Log-rank value = 13.70, P 〉 0.05 ）. There were no significant differences in the body temperature, respiration, heart rate, systolic blood pressure and diastolic blood pressure before and after medication between the 2 groups （Z = 0. 03, 0. 68, 0. 97, 0. 22, 0. 72, P 〉 0.05）. There were no significant differences in the number of patients with abnormal results of blood test, hepatic function, renal function and electrocardiogram between the 2 groups （P 〉 0.05 ）. No severe adverse event was observed in the clinical trial. Conclusion Houpupaiqi mixture significantly promotes the recovery of gastrointestinal function of the patients who underwent open gastrointestinal surgery with relatively low adverse events.