特利加压素对顽固性肝硬化腹水的治疗作用与效应特点观察被引量：18

Observation of the therapeutic and characteristic effects of terlipressin on refractory cirrhotic ascites

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摘要目的观察特利加压素对肝硬化顽固性腹水(RA)的疗效作用及急性肾损伤(AKI)对该作用的影响。方法采用非随机对照临床试验,收集上海中医药大学附属曙光医院、上海市宝山区中西医结合医院、湖北省中山医院、郑州大学第一附属医院、浙江大学附属第一医院及上海市浦东新区人民医院等2015年3月至2017年3月间收治的111例肝硬化伴RA住院患者资料,分为常规治疗组(对照组)26例,其中RA未合并AKI(RA-NAKI)与RA合并AKI(RA-AKI)患者各13例,治疗包括利尿、补充白蛋白及合并细菌感染者使用抗菌药物等;特利加压素联合治疗组(特利组)85例,其中RA-NAKI患者27例,RA-AKI患者58例,在对照组基础上,加用特利加压素1 mg静脉滴注或微泵静脉推注(每12 h 1次~每6 h 1次)5 d以上。治疗2周,随访4周。比较各组治疗前、治疗1周、2周及随访4周的超声检测仰卧位肝前腹水及最深腹水的深度、体质量、24 h尿量、腹围、平均动脉压(MAP)、肝肾功能等。计数资料用χ^2检验。基线4组样本比较,正态分布资料采用单因素方差分析,非正态分布资料用Kruskal-Wallis H检验。采用重复测量方差分析,比较组内治疗前后不同时点序列疗效差异。组内两两比较采用单因素方差分析LSD法;两组间不同时点序列疗效差异比较采用独立样本t检验;两组非正态分布资料间比较采用Mann-Whitney秩和检验。结果(1)特利组和对照组的RA-NAKI与RA-AKI亚组共4组间基线资料比较:对照组的年龄高于特利组,RA-AKI组的血清肌酐(SCr)高于RA-NAKI组,其余基线资料与合并用药等差异均无统计学意义(P值均>0.05)。(2)特利组与对照组治疗前后组内比较:患者体质量、腹围及最深腹水降低、血清白蛋白均有升高(P<0.05);特利组24 h尿量、MAP明显增加,肝前腹水、SCr及Child-Turcotte-Pugh(CTP)评分降低。治疗前后差值的2组间比较,特利组治疗及随访期体质量、腹围、肝前腹水及最深腹水降低,MAP增加,均较同时点对照组差异有统计学意义(P值均<0.05);特利组治疗期间24 h尿量增加较对照组差异有统计学意义(P值均<0.05);特利组治疗2周、随访4周SCr及CTP降低较对照组差异均有统计学意义(P值均<0.05)。(3)特利组内RA-AKI与RA-NAKI两个亚组间,前者基线SCr值高于后者,治疗后体质量、腹围、肝前腹水、最深腹水及CTP评分均有降低;RA-AKI组可见24 h尿量、MAP明显增加,SCr明显降低,血清白蛋白浓度升高。2亚组间治疗前后差值比较,RA-AKI组治疗1、2周及随访4周体质量减轻均较RA-NAKI组明显,分别为(-2.3±0.2)kg比(-1.5±0.2)kg、(-4.1±0.2)kg比(-2.6±0.2)kg、(-4.2±0.3)kg比(-2.4±0.3)kg;治疗2周及随访4周尿量增加较RA-NAKI组明显,分别为(468±42)ml比(110±131)ml、(272±34)ml比(11±112)ml;随访4周SCr降低较RA-NAKI组差异有统计学意义(P<0.05),为(18.3±4.7)μmol/l比(0.9±2.4)μmol/l。结论在常规治疗基础上,加用特利加压素可明显增加肝硬化顽固性腹水患者MAP与24 h尿量、改善肾功能与促进腹水消退,对合并AKI患者的作用更为明显。不良反应轻微。 Objective To observe the therapeutic effect of terlipressin on refractory ascites(RA)in cirrhosis,and its role and impact on acute kidney injury(AKI).Methods A non-randomized controlled clinical trial data of 111 hospitalized cases of liver cirrhosis accompanied with RA was collected from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Zhongshan Hospital of Hubei Province,The First Affiliated Hospital of Zhengzhou University,The First Affiliated Hospital of Medical School of Zhejiang University,and People's Hospital of Pudong New Area of Shanghai between March 2015 and March 2017.26 cases of conventional treatment group(control group)were divided into two subgroups:RA without AKI(RA-NAKI)and RA with AKI(RA-AKI),and each subgroup consisted 13 cases.Patients with bacterial infection were treated with diuretics,albumin supplementation and antibiotics.85 cases were presented in terlipressin combined treatment group,of which 27 cases were of RA-NAKI and 58 cases were of RA-AKI.Control group was injected terlipressin 1mg of intravenous drip or static push(once q6 h^12 h)for more than 5 days.The treatment duration lasted for 2 weeks with 4 weeks of follow-up.Body weight,24-hour urine volume,abdominal circumference,mean arterial pressure(MAP),liver and kidney function,anterior hepatic ascites,deepest point of ascites,and ultrasonographic detection of ascites in supine position before treatment,one and two weeks after treatment and 4 weeks after follow-up were compared.Count data were tested by χ^2.Samples of four groups at baseline were compared.One-way analysis of variance was used for normal distribution data and Kruskal-Wallis H test for non-normal distribution data.Repeated measures analysis of variance was used to compare the difference in efficacy between different time points before and after treatment in the group.The LSD method of one-way ANOVA was used to compare the two groups.A t-test of independent samples was used to compare the efficacy of different time series between the two groups.Mann-Whitney rank-sum test was used to compare the data of non-normal distribution between the two groups.Results(1)Baseline data were compared among 4 subgroups of terlipressin RA-NAKI and control RA-AKI.Control group age was higher than that of terlipressin group,and the serum creatinine(SCr)of the RA-AKI group was higher than RA-NAKI group,and there was no significant difference in the rest of the baseline data and the combined medication(P>0.05).(2)An intra-group comparison between control and trelipressin before and after treatment showed that all patients had lower body mass,abdominal circumference and deepest ascites,and higher serum albumin(P<0.05).24-hour urine volume and MAP was significantly increased in the terlipressin group,while the pre-ascites,SCr and child Turcotte Pugh(CTP)scores were decreased.Body weight,abdominal circumference,pre-ascites,and deepest ascites of the terlipressin group were decreased,while MAP was increased during the treatment and follow-up periods.The differences were statistically significant when compared with the control group at the same time(P<0.05).There was a statistically significant difference in the increase of 24-h urine volume in the terlipressin group compared with the control group(P<0.05).The decrease in SCr and CTP in the terlipressin group after 2 weeks of treatment and 4 weeks of follow-up was statistically significant compared with the control group(P<0.05).(3)Among the two subgroups of RA-AKI and RA-NAKI in the terlipressin group,the baseline SCr value of the former was higher than that of the latter.After treatment,the body weight,abdominal circumference,pre-ascites,deepest ascites and CTP scores were decreased.In the RA-AKI group,24-hour urine volume,MAP,SCr and serum albumin concentration were significantly increased.The difference between the two subgroups before and after treatment was compared,and the body weight of RA-AKI group at 1,2 weeks of treatment and 4 weeks of follow-up was significantly lower than RA-NAKI group,which were(-2.3±0.2 vs.-1.5±0.2)kg,(-4.1±0.2 vs.-2.6±0.2)kg,(-4.2±0.3 vs.-2.4±0.3)kg,respectively.RA-NAKI group urine volume was significantly increased at 2 weeks of treatment and 4 weeks of follow-up,which was(468±42 vs.110±131)ml,(272±34 ml vs.11±112)ml,respectively.SCr reduction(18.3±4.7 vs.0.9±2.4)µmol/l at 4 weeks of follow-up was apparent in RA-NAKI group,and the difference was statistically significant(P<0.05).Conclusion Addition of terlipressin to conventional treatment may significantly increase MAP,24-h urine volume,improve renal function and promote ascites resolution in patients with refractory cirrhotic ascites.Moreover,its combination effect is more obvious in AKI patients,and adverse reactions are mild.

作者邢枫李爽张建军孙长宇黄建荣高泽立朱亭亭赵强张华刘成海 Xing Feng;Li Shuang;Zhang Jianjun;Sun Changyu;Huang Jianrong;Gao Zeli;Zhu Tingting;Zhao Qiang;Zhang Hua;Liu Chenghai(Second Department of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Institute of Liver Diseases,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Gastroenterology,Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 201900,China;Department of Integrated Liver Diseases,Zhongshan Hospital of Hubei Province,Wuhan 430033,China;Department of Infectious Diseases,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Infectious Diseases,The First Affiliated Hospital,Zhejiang University,Hangzhou 310003,China;Department of Gastroenterology,Pudong New Area Hospital,Shanghai 201299,China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai 201203,China;Shanghai Innovation Center of TCM Health Service,Shanghai 201203,China)