脓毒症临床前研究最低质量标准(MQTiPSS):基于液体复苏和抗菌药物治疗终点的质量标准(全译)  

Minimum quality threshold in preclinical sepsis studies(MQTiPSS):quality threshold for fluid resuscitation and antimicrobial therapy endpoints

作　　者：陈欢 张华莉 王慷慨 姚咏明[2] 肖献忠 Chen Huan;Zhang Huali;Wang Kangkai;Yao Yongming;Xiao Xianzhong(Sepsis Translational Medicine Key Laboratory of Hunan Province,Department of Pathophysiology,School of Basic Medicine Science,Central South University,Changsha 410078,Hunan,China;Trauma Research Center,Fourth Medical Center of the Chinese PLA General Hospital,Beijing 100048,China)

机构地区：[1]中南大学基础医学院病理生理学系,脓毒症转化医学湖南省重点实验室,长沙410078 [2]解放军总医院第四医学中心创伤研究中心,北京100048

出　　处：《中华危重病急救医学》2019年第11期1307-1316,共10页Chinese Critical Care Medicine

基　　金：国家自然科学基金(81671895,81871610,81730057)。

摘　　要：正如《国际脓毒症和脓毒性休克管理指南:2016》所述,初始液体复苏及使用抗菌药物是脓毒症和脓毒性休克早期治疗的关键步骤。然而,脓毒症临床前模型中不存在这样明确的指南。为解决这些不足,2017年5月在维也纳召开了脓毒症临床前建模的韦格斯-伯纳德会议。与会者对2003至2012年间所发表的260篇关于脓毒症模型的高被引科研论文进行了文献综述。该综述表明超过70%的实验没有使用或者报告液体复苏和(或)抗菌药物治疗。这些信息是为脓毒症临床前建模提出一系列"推荐"和"考虑"建议的基础;本文(第三部分)详细阐述了脓毒症模型中应该强调的关于液体复苏和抗菌药物治疗的"推荐"与"考虑"建议。与人类脓毒症类似,推荐在实验模型中进行液体复苏,除非它是研究液体复苏时的对照组。复苏时首选等渗晶体液。给药途径和给药时机应该根据模型的具体要求进行调整,优先考虑对血流动力学进行动态监测而不是静态监测。应该考虑使用预先确定的终点进行液体复苏并避免液体超负荷。脓毒症临床前研究显示,抗菌药物的使用存在严重的不一致。为弥补这一缺陷,推荐在临床前研究中使用抗菌药物,并且根据具体的脓毒症模型及病原体选择抗菌药物和剂量。理想情况下,抗菌药物的使用应该密切模拟临床实践,并要考虑药物的药代动力学特征、吸收、分布和清除率的变化,以及年龄、体重、并发症等宿主因素。这些"推荐"和"考虑"建议被认为是脓毒症动物模型的"最佳实践",应该得到执行。As outlined in the International Guidelines for Management of Sepsis and Septic Shock:2016,initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock.However,such clear guidelines do not exist for preclinical sepsis models.To address these shortcomings,the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017.The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models.The review demonstrated that over 70%of experiments either did not use or failed to report resuscitation and/or antibiotic treatment.This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models;this PartⅢreport details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models.Similar to human sepsis,fluid resuscitation is recommended in the experimental setting unless part of the study.Iso-osmolar crystalloid solutions are preferred.The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring.Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered.Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols.To remedy this,antimicrobials are recommended for preclinical studies,with choice and dose adjusted to the specific sepsis model and pathogen(s).Ideally,the administration of antimicrobials should closely mimic clinical practice,taking into account the drug's pharmacokinetic profile,alterations in absorption,distribution and clearance,and host factors such as age,weight,and comorbidities.These recommendations and considerations are proposed as"best practices"for animal models of sepsis that should be implemented.

关 键 词：抗菌药物治疗 液体复苏 脓毒症临床前研究最低质量标准(MQTiPSS) 脓毒症模型 脓毒症 脓毒性休克 

分 类 号：R45[医药卫生—治疗学]