近五年中医药干预脓毒症心肌损伤随机对照试验结局指标的分析Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention of sepsis-induced myocardial injury in recent five years
梁立新;刘子豪;龙德怀;刘红旭;
LIANG Li-xin;LIU Zi-hao;LONG De-huai;LIU Hong-xu;Beijing Hospital of Traditional Chinese Medicine, Capital Medical University;Shunyi Branch, Beijing Hospital of Traditional Chinese Medicine;
摘要(Abstract):
该研究分析了近五年中医药干预脓毒症心肌损伤随机对照试验(RCT)的结局指标,为构建中医药治疗脓毒症心肌损伤的核心指标集提供依据。全面检索4个中文数据库、3个英文数据库、2个临床试验方案注册中心,收集近五年中医药治疗脓毒症心肌损伤的RCT,使用Cochrane的ROB评价表对纳入研究进行质量评价,分析结局指标。最终纳入42项研究,包括2项临床试验注册方案。研究发现,42项研究总体偏倚风险较高,所有纳入研究结局指标包括“临床有效率、中医证候积分、病情程度、炎症、心肌标志物、心脏结构及血流动力学、心电图、免疫功能、代谢及肝肾功能、安全性”等10类共86个结局指标。心肌标志物为出现频次最高的结局指标,其次为心脏结构及血流动力学指标,共8项RCTs报告了中医证候积分。进一步研究发现,中医药干预脓毒症心肌损伤的结局指标选取存在以下问题:结局指标主次不分;轻视终点结局指标,替代指标选取不合理;忽视中医特色指标;缺少对患者免疫状态的评估;对经济学及安全性指标关注不足。因此,应根据有效性试验核心结局指标(COMET)工作组的建议,构建中医药干预脓毒症心肌损伤的临床研究核心指标集,方便临床研究者选取合适的结局指标,便于同类临床研究结论的合并,促进中医药特色治疗措施的推广。
This study aims to analyze the outcome indicators of randomized controlled trial(RCT) on traditional Chinese medicine(TCM) intervention of sepsis-induced myocardial injury(SIMI) in recent five years, which is expected to lay a basis for the construction of core outcome set(COS) for this disease treated by TCM. To be specific, RCT on the treatment of SIMI with TCM was retrieved from 4 Chinese databases, 3 English databases, and 2 clinical trial protocol registries. The quality of the included studies was evaluated with Cochrane risk-of-bias(ROB) tool, and the outcome indicators were analyzed. Finally, 42 RCTs were included, of which 2 were clinical trial registration schemes. The study found that 42 RCTs had a high risk of bias, and reported a total of 86 indicators in "clinical effective rate, disease severity, TCM syndrome score, inflammation, myocardium, cardiac structure and hemodynamics, electrocardiogram, immunology, metabolism and liver and kidney function, and safety". Outcome indicators on myocardium had the highest emergence frequency, followed by indicators on the cardiac structure and hemodynamics. A total of 8 RCTs reported TCM syndrome scores. Further analysis suggested the following problems in the selection of outcome indicators in the RCTs on TCM intervention of SIMI: no classification of primary and secondary indicators, disregard of endpoint indicators, irrational selection of alternative indicators, neglection of TCM characteristics, no assessment of patients′ immune status, and no emphasis on economic indicators and safety indicators. Therefore, according to the recommendations of the core outcome measures in effectiveness trials(COMET) working group, a COS for TCM intervention of TCM for SIMI should be developed, so as to facilitate clinical researchers to select appropriate outcome indicators, the combination of conclusions of similar clinical studies, and the promotion of TCM interventions.
关键词(KeyWords):
中医药;脓毒症;心肌损伤;随机对照试验;结局指标
traditional Chinese medicine;sepsis;myocardial injury;randomized controlled trial;outcome indicator
基金项目(Foundation): 国家中医药管理局中医药循证能力建设项目(2019XZZX-XXG001);; 北京市医院管理局重点医学专业发展计划项目(ZYLX201817)
作者(Authors):
梁立新;刘子豪;龙德怀;刘红旭;
LIANG Li-xin;LIU Zi-hao;LONG De-huai;LIU Hong-xu;Beijing Hospital of Traditional Chinese Medicine, Capital Medical University;Shunyi Branch, Beijing Hospital of Traditional Chinese Medicine;
DOI: 10.19540/j.cnki.cjcmm.20220529.503
参考文献(References):
- [1] 曹钰,柴艳芬,邓颖,等.中国脓毒症/脓毒性休克急诊治疗指南(2018)[J].临床急诊杂志,2018,19(9):567.
- [2] MARTIN G S,MANNINO D M,EATON S,et al.The epidemio-logy of sepsis in the United States from 1979 through 2000[J].N Engl J Med,2003,348(16):1546.
- [3] COHEN J,VINCENT J L,ADHIKARI N,et al.Sepsis:a roadmap for future research[J].Lancet Infect Dis,2015,15(5):581.
- [4] LV X,WANG H.Pathophysiology of sepsis-induced myocardial dysfunction[J].Mil Med Res,2016,3(4):10.
- [5] 梁立新,吴彦青,狄浩然,等.当代医家论治脓毒症心肌抑制经验探析[J].北京中医药,2017,36(5):439.
- [6] 刘清泉,张伟,姜良铎.瘀毒伤络、阻络病机与脓毒症[J].中国中医药现代远程教育,2010,8(17):199.
- [7] ZHAO G Z,CHEN R B,LI B,et al.Clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis[J].Ann Transl Med,2019,7(6):122.
- [8] 李静.临床试验设计:随机对照[J].中国循环杂志,2017,32(11):1126.
- [9] 曾于珍,陈世耀.临床研究结局指标选择与样本量估计[J].协和医学杂志,2018,9(1):87.
- [10] 邱瑞瑾,陈诗琪,韩松洁,等.基于COMET数据库的核心指标集研究现状及进展[J].中国循证医学杂志,2019,19(5):622.
- [11] 龙敏,张玉琴,岳煜,等.黄连解毒汤联合西药治疗脓毒症心肌损伤疗效研究[J].陕西中医,2022,43(3):329.
- [12] 李莹莹,袁康,何明丰,等.参附注射液治疗脓毒症心肌损伤的临床疗效分析[J].中医药学报,2022,50(3):72.
- [13] 黄亚秀,李少萍,黄永莲,等.基于Th17/Treg免疫失衡研究茯苓四逆汤对脓毒症心肌病患者的影响[J].深圳中西医结合杂志,2021,31(12):15.
- [14] 陈仁山,刘宁,王帅,等.益气凉血化瘀法治疗脓毒症心功能障碍及对血浆炎症因子和心功能的影响[J].中医临床研究,2021,13(7):82.
- [15] 林晓君,徐维彪,陈东升,等.中西医结合治疗老年人脓毒症心肌损伤的效果[J].深圳中西医结合杂志,2021,31(23):47.
- [16] 叶志桥,余青,曾萍,等.参附注射液联合左卡尼汀对脓毒症休克合并心肌损伤(心肾阳虚型)患者的临床疗效观察[J].心血管病防治知识,2020,10(24):32.
- [17] 胡娟,曹平,全瑶,等.川芎嗪对脓毒症心肌损伤患者血清和肽素、心型脂肪酸结合蛋白及心脏舒缩功能的影响[J].中国急救复苏与灾害医学杂志,2020,15(11):1292.
- [18] 杨梁,彭晓峰,曾剑,等.耳穴贴压对脓毒症心肌抑制的保护作用研究[J].现代中西医结合杂志,2020,29(10):1058.
- [19] 韩桢,王国兴.芪参活血颗粒在治疗脓毒症合并心肌损伤中的作用[J].中国医师杂志,2020,22(1):26.
- [20] 彭晓洪,黄永莲,黄亚秀,等.温脾汤对脓毒症心肌损伤患者核转录因子-κB的影响[J].中医药临床杂志,2020,32(10):1906.
- [21] 廖云海,卢静,王志民,等.血必净注射液对脓毒症心肌保护的临床研究[J].中国医药科学,2020,10(22):55.
- [22] 韩勇,刘德红,陈伟峰,等.血必净注射液对严重脓毒症心肌抑制的疗效及对血清生化指标的影响研究[J].中国实用医药,2020,15(15):16.
- [23] 王大力,刘源,杨浩,等.血必净注射液联合注射用益气复脉治疗脓毒症心功能障碍临床效果观察[J].临床误诊误治,2020,33(11):35.
- [24] 冯艳,陈德珠,钟建,等.血必净注射液治疗脓毒症合并心肌功能障碍患者的疗效和安全性[J].中国实用医药,2020,15(17):124.
- [25] 常晓,王玲,曾子华,等.益气活血汤联合西医常规疗法治疗脓毒症心肌损伤35例[J].中医研究,2020,33(9):15.
- [26] 何聪,龙玲,杜全胜,等.参麦注射液在脓毒症心肌损伤患者中的作用[J].河北医科大学学报,2019,40(7):785.
- [27] 韦海,陈品建,王益旺.锦红汤联合西药常规治疗脓毒症早期心肌损伤的临床观察[J].云南中医中药杂志,2019,40(11):45.
- [28] 明自强,俞林明.生脉联合左西孟旦治疗急性脓毒性心肌损伤疗效观察[J].心脑血管病防治,2019,19(2):145.
- [29] 夏瑞.舒血宁注射液在严重脓毒症心肌损伤治疗中的应用效果分析[J].北方药学,2019,16(2):124.
- [30] 董妍,董旭,于盼盼,等.温阳化瘀解毒法治疗脓毒症心功能障碍的临床观察[J].中国实验方剂学杂志,2019,25(14):125.
- [31] 董妍,董旭,于盼盼,等.温阳化瘀解毒法治疗脓毒症心肌抑制的临床研究[J].辽宁中医杂志,2019,46(7):1470.
- [32] 朱瑾,刘绛云,倪海滨,等.心脉隆注射液对脓毒性心肌病机械通气患者心脏功能的影响[J].中国新药杂志,2019,28(7):828.
- [33] 罗苑苑,赵馥,陈伟焘,等.心脉隆注射液对脓毒症心肌损伤病人血清脂联素和心率变异性的影响[J].中西医结合心脑血管病杂志,2019,17(3):403.
- [34] 李兴华,程连房,李桂仙,等.心脉隆注射液治疗脓毒症性心功能障碍的疗效观察[J].世界中西医结合杂志,2019,14(12):1716.
- [35] 杨金亮,刘善伟,刘玉霞.新四逆汤对脓毒症心肌顿抑患者无创血流动力学的影响[J].世界中西医结合杂志,2019,14(8):1160.
- [36] 陈德珠,钟建,冯艳,等.血必净注射液对脓毒症性心肌功能障碍的临床干预研究[J].哈尔滨医药,2019,39(6):549.
- [37] 郑坚,吴云龙,王梅,等.左西孟旦联合中药制剂治疗严重脓毒症心肌损伤患者的临床效果[J].中华医院感染学杂志,2019,29(1):44.
- [38] 罗苑苑,赵馥,陈伟焘,等.参附注射液对脓毒症患者心肌损伤的临床研究[J].中国中医急症,2018,27(11):1930.
- [39] 刘文悦,魏晓华,卢清龙,等.参麦注射液辅治脓毒症患者心肌抑制的疗效及对心肌标志物的影响[J].疑难病杂志,2018,17(9):873.
- [40] 李勇,宋薇.连续性血液净化联合益气活血法对脓毒症伴心肌功能障碍患者的临床疗效观察[J].东南国防医药,2018,20(3):225.
- [41] 刘文悦,魏晓华,杨丽丽,等.乌司他丁联合参麦注射液治疗脓毒症心肌抑制作用及其抗氧化机制研究[J].中国临床医生杂志,2018,46(12):1453.
- [42] 卢静,肖斌,苏天生,等.血必净联合乌司他丁对脓毒症心肌损伤的保护效应[J].现代中西医结合杂志,2018,27(24):2653.
- [43] 高红雨,张岚.自拟活血解毒汤对脓毒症心力衰竭患者血清心肌肌钙蛋白Ⅰ及心肌酶学和临床指标的影响[J].现代中西医结合杂志,2018,27(31):3459.
- [44] 褚永果,齐洪娜,刘晓婷,等.红花黄色素治疗严重脓毒症患者的心肌损伤[J].中成药,2017,39(4):706.
- [45] 张萌,段美丽,李昂.芪参活血颗粒治疗脓毒症心肌损伤的随机对照临床研究[J].北京中医药,2017,36(9):785.
- [46] 齐洪娜,张建军,何佳起,等.舒血宁治疗严重脓毒症心肌抑制患者的效果及对心脏型脂肪酸结合蛋白和炎性因子的影响[J].中国医药,2017,12(1):36.
- [47] 韩斌,郑文香,曹新河,等.心脉隆注射液对脓毒症心肌损伤保护作用的临床观察[J].中西医结合心脑血管病杂志,2017,15(21):2798.
- [48] 王郁竹.心脉隆注射液对脓毒症心肌抑制的临床疗效观察[D].昆明:昆明医科大学,2017.
- [49] 张宏伟,魏立友,赵刚,等.血必净注射液对老年脓毒症患者心肌损伤的保护作用[J].中国老年学杂志,2017,37(19):4863.
- [50] 黄柏文.中药联合艾司洛尔对脓毒症患者心肌抑制的干预效果分析[J].蛇志,2017,29(2):146.
- [51] 朱君瑶.四逆汤合升陷祛瘀汤对脓毒症心肌抑制患者的干预作用临实验[EB/OL].(2020-09-28)[2022-04-17].https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR20000 35556.
- [52] 王评.茯苓四逆汤对脓毒症心肌病免疫麻痹干预的临床研究[EB/OL].(2021-11-28)[2022-04-17].https://www.chictr.org.cn/hvshowproject.aspx?id=114887.
- [53] 郑筱萸.中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002.
- [54] 李志军,刘清泉,沈洪,等.脓毒症中西医结合诊治专家共识[J].中华危重病急救医学,2013,25(4):194.
- [55] 张颖,贾丽燕,邵建柱,等.中医药临床研究中实施盲法的原则、问题和评价[J].北京中医药,2018,37(12):1159.
- [56] SINGER M,DEUTSCHMAN C S,SEYMOUR C W,et al.The third international consensus definitions for sepsis and septic shock (sepsis-3)[J].JAMA,2016,315(8):775.
- [57] 中华医学会重症医学分会.中国严重脓毒症/脓毒性休克治疗指南(2014)[J].中华内科杂志,2015,54(6):557.
- [58] RPHILLIP D,MITCHELL M L,ANDREW R,et al.Surviving sepsis campaign:international guidelines for management of severe sepsis and septic shock,2012[J].Intensive Care Med,2013,39(2):165.
- [59] 李娟珍,王莹.脓毒症心肌抑制的临床诊断[J].中国小儿急救医学,2016,23(8):556.
- [60] 慕婉晴,顾国嵘.降钙素原(PCT)在脓毒症临床诊断治疗中作用的研究进展[J].复旦学报(医学版),2019,46(1):1672.
- [61] KNAUS W A,DRAPER E A,WAGNER D P,et al.APACHE Ⅱ:a severity of disease classification system[J].Crit Care Med,1985,13(10):818.
- [62] SHARMA Z,BALE C,KAKRANI A,et al.Sequential organ fai-lure assessment score as prognostic marker in critically ill patients in a tertiary care intensive care unit[J].Int J Public Health,2013,3(3):155.
- [63] 李慧敏,熊兴江,胡瑞学,等.中医药治疗急性心肌梗死随机对照试验结局指标的现状分析[J].中医杂志,2021,62(5):405.
- [64] 任丽丽,戴国华,高武霖,等.中医临床疗效评价替代指标的替代机制研究思路[J].中华中医药杂志,2021,36(6):3089.
- [65] 张明妍,李凯,蔡慧姿,等.临床试验核心指标集研究发展概况及其在中医药领域的关键问题[J].中医杂志,2021,62(2):108.
- [66] 管慧,戴国华,宋超,等.中医临床疗效评价替代指标的选择思路与方法[J].中华中医药杂志,2021,36(5):2807.
- [67] 王桂倩,郑慧娟,曹迎,等.近两年中医药干预脓毒症胃肠功能障碍临床试验结局指标的分析[J].中国中药杂志,2022,47(3):819.
- [68] 许煊,王猛.脓毒症的免疫抑制[J].国际儿科学杂志,2018,45(11):817.
- [69] 张时浩,潘郭海容,冯文佳,等.基于急性虚证探讨脓毒症免疫紊乱机制[J].长春中医药大学学报,2022,38(3):341.
- [70] 吴健锋,栾樱译,柯路.脓毒症免疫抑制诊治专家共识[J].中华危重病急救医学,2020,32(11):1281.
- [71] 杨吉明.医疗费用控制与卫生经济学的基石研究[J].行政事业资产与财务,2019,18(9):1.
- [72] 宫晓,魏竞竞,付国静,等.近五年中医药干预紧张型头痛随机对照试验结局指标现状分析[J].中国中药杂志,2021,46(18):4591.
- [73] 郑颂华,吴泰相,商洪才,等.中药复方临床随机对照试验报告规范2017-CONSORT声明的扩展、说明与详述[J].中西医结合心脑血管病杂志,2019,17(1):1.
- 中医药
- 脓毒症
- 心肌损伤
- 随机对照试验
- 结局指标
traditional Chinese medicine - sepsis
- myocardial injury
- randomized controlled trial
- outcome indicator
- 梁立新
- 刘子豪
- 龙德怀
- 刘红旭
LIANG Li-xin- LIU Zi-hao
- LONG De-huai
- LIU Hong-xu
- Beijing Hospital of Traditional Chinese Medicine
- Capital Medical University
- Shunyi Branch
- Beijing Hospital of Traditional Chinese Medicine
- 梁立新
- 刘子豪
- 龙德怀
- 刘红旭
LIANG Li-xin- LIU Zi-hao
- LONG De-huai
- LIU Hong-xu
- Beijing Hospital of Traditional Chinese Medicine
- Capital Medical University
- Shunyi Branch
- Beijing Hospital of Traditional Chinese Medicine