脓毒症临床前研究最低质量标准(MQTiPSS):基于感染类型和器官功能障碍终点的质量标准(全译)

Minimum quality threshold in preclinical sepsis studies(MQTiPSS):quality threshold for types of infections and organ dysfunction endpoints

虽然脓毒症的临床定义和推荐治疗指南在定期更新,但对脓毒症的临床前模型尚无系统综述.为了弥补这一缺陷,韦格斯-伯纳德会议的与会人员对260篇关于脓毒症模型的高被引科研论文(2003至2012年)进行了文献综述,并提出了一套指南.本报告的第二部分为针对脓毒症临床前模型的感染类型和器官损伤类型提出的建议.在感染类型方面,本综述纳入的研究中44%采用盲肠结扎穿孔术(CLP)模型,40%采用内毒素注射模型.推荐8(按指南第一部分顺序编号):内毒素注射不是复制脓毒症模型的合适方法;从临床分离物中提取的活菌或真菌菌株更为合适.推荐9:尽可能使用人体脓毒症中常见的微生物复制脓毒症模型.脓毒症3.0定义指出,脓毒症是由宿主对感染反应失调所致危及生命的器官功能障碍,但本综述对器官功能障碍的描述很有限.推荐10 :在临床前模型中应该使用器官功能障碍的定义.推荐11 :并非某一器官/系统的所有功能活动异常才能诊断为器官功能障碍.推荐12 :应采用客观的可重复评分系统来评估器官功能障碍.推荐13 :并非所有实验都必须检测器官功能障碍的全部指标,但是研究者应尽可能多地收集相关信息.这些推荐意见被认为是脓毒症动物模型的"最佳实践"指南.

Although the clinical definitions of sepsis and recommended treatments are regularly updated,a systematic review has not been done for preclinical models.To address this deficit,a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations.This PartⅡreport provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models.Concerning the types of infections,the review showed that the cecal ligation and puncture model was used for 44%of the studies while 40%injected endotoxin.Recommendation#8(numbered sequentially from PartⅠ):endotoxin injection should not be considered as a model of sepsis;live bacteria or fungal strains derived from clinical isolates are more appropriate.Recommendation#9:microorganisms should replicate those typically found in human sepsis.Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection,but the review of the papers showed limited attempts to document organ dysfunction.Recommendation#10:organ dysfunction definitions should be used in preclinical models.Recommendation#11:not all activities in an organ/system need to be abnormal to verify organ dysfunction.Recommendation#12:organ dysfunction should be measured in an objective manner using reproducible scoring systems.Recommendation#13:not all experiments must measure all parameters of organ dysfunction,but investigators should attempt to fully capture as much information as possible.These recommendations are proposed as"best practices"for animal models of sepsis.