脓毒症3.0课件

脓毒症3.0孙仁华孙仁华浙江省人民浙江省人民(RNMN)医院医院ICU2016-10 脓毒症脓毒症3.0“面面观面面观”第一页，共四十二页。脓毒症3.0严重(ynzhng)脓毒症及脓毒性休克流行病学严重脓毒症患者死亡(swng)风险为34%，脓毒性休克患者死亡风险为50%。第二页，共四十二页。脓毒症3.0新近流调显示新近流调显示(xinsh)脓毒性休克死亡率下降脓毒性休克死亡率下降 结果发现，重症感染患者的绝对死亡率从 35.0% 下降(xijing)到了 18.4%，总死亡率下降了 16.6%，年绝对死亡率下降了 1.3%，相对风险下降了 47.5%。JAMA. 2014 Apr 2;311(13):1308-16.第三页，共四十二页。脓毒症3.0脓毒症定义脓毒症定义(dngy)变迁（变迁（1.0） Sepsis 1.0=感染(gnrn)SIRSChest 1992 Jun; 101(6):1644-55创伤创伤烧伤烧伤胰腺炎胰腺炎缺血缺血sepsisSEVERESEPSIS细菌细菌其他其他病毒病毒原虫原虫真菌真菌其他其他第四页，共四十二页。脓毒症3.0脓毒症定义脓毒症定义(dngy)变迁（变迁（2.0）Intensive Care Med. 2003 Apr;29(4):530-8. Epub 2003 Mar 28. Sepsis 2.0=感染SIRS 会议提出(t ch)了包括20余条临床症状和体征评估指标构成的诊断标准，即Sepsis 2.0。然而该标准过于复杂，且缺乏充分的研究基础和科学研究证据支持，并未得到临床认可和应用。创伤创伤烧伤烧伤胰腺炎胰腺炎缺血缺血sepsisSEVERESEPSIS细菌细菌其他其他病毒病毒原虫原虫真菌真菌其他其他第五页，共四十二页。脓毒症3.0Diagnostic criteria for sepsis第六页，共四十二页。脓毒症3.0The PIRO system for staging sepsis第七页，共四十二页。脓毒症3.02012SSC指南指南(zhnn)发展发展Critical care medicine 2004 Mar; 32(3):858-73.Critical care medicine 2008 Jan; 36(1):296-327.Crit Care Med. 2013 Feb;41(2):580-637.20082004第八页，共四十二页。脓毒症3.0脓毒症诊断标准脓毒症诊断标准(biozhn)的的“争议争议”方法：方法：通过对2000 年至2013 年澳大利亚和新西兰172 个重症加强治疗病房(ICU)近120 万例患者的数据分析，根据是否满足2条全身炎症反应综合征(SIRS)的诊断标准将感染伴器官功能障碍的患者分为SIRS 阳性和SIRS 阴性两组。结果：结果：在近11万例感染伴器官功能障碍的患者中，87.9%为SIRS阳性，12.1%为SIRS 阴性，在14年内两组患者的临床(ln chun)特征和病死率变化相似。校正分析显示，患者病死率随着满足SIRS标准项目的增加呈线性增高。结论：该研究说明现有脓毒症标准有可能遗漏结论：该研究说明现有脓毒症标准有可能遗漏约约 1/8 的感染伴器官功能障碍患者的感染伴器官功能障碍患者，且该标准不能且该标准不能确定病死率增加的临界点，这确定病死率增加的临界点，这提示当前脓毒症的提示当前脓毒症的筛查标准的特异性不佳。筛查标准的特异性不佳。 N Engl J Med, 2015, 372 (17): 1629-1638. 第九页，共四十二页。脓毒症3.0Do we need a new definition of sepsis? the definition of septic shock currently revolves around variable blood pressure and/or lactate levels, with loosely termed or undefined adequacy of fluid resuscitation and persistent hypotension. Defining sepsis must, however, be an ongoing iterative process requiring minor or major revisions as new findings come to light. In much the same way that software enhancements move from version 1.0 to 1.1 or to 2.0 depending on the magnitude of change, so a new sepsis 3.0 definition must be refined into versions 3.1, 3.2, and so on until an eventual complete overhaul generates the development of sepsis 4.0.Intensive Care Med, 2015, 41 (5): 909-911. 脓毒症的诊断标准于脓毒症的诊断标准于19911991年年发布发布（脓毒症脓毒症1.01.0）, ,但过于但过于(guy)(guy)敏感敏感，可能导致脓毒症的过度可能导致脓毒症的过度诊断和治疗；诊断和治疗；20012001年更新版年更新版（脓毒症脓毒症2.02.0）又过于复杂又过于复杂，未被广泛应用，未被广泛应用。 第十页，共四十二页。脓毒症3.0脓毒症脓毒症3.0. 2016年年第十一页，共四十二页。脓毒症3.0 Sepsis 3.0“应运而生应运而生(yng yn r shng)”JAMA. 2016 Feb 23;315(8):801-10第十二页，共四十二页。脓毒症3.0Sepsis 3.0定义定义(dngy)JAMA. 2016 Feb 23;315(8):801-10Mortality 10%第十三页，共四十二页。脓毒症3.0Sepsis 3.0InfectionSOFA2Sepsis 3.0诊断诊断(zhndun)标准标准JAMA. 2016 Feb 23;315(8):801-10第十四页，共四十二页。脓毒症3.0Septic shock 定义定义(dngy)及诊断标准及诊断标准JAMA. 2016 Feb 23;315(8):801-10Mortality 40%Septic shock=Sepsis+输液(shy)无反应低血压+使用缩血管药物维持MAP65mmHg）+乳酸则2mmol/L。Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. 第十五页，共四十二页。脓毒症3.0脓毒症脓毒症3.0诊断诊断(zhndun)流程流程JAMA. 2016 Feb 23;315(8):801-10第十六页，共四十二页。脓毒症3.0Sepsis 3.0第十七页，共四十二页。脓毒症3.0ACCP反对反对(fndu)Sepsis 3.01.Given that use of the current definitions results in saving lives, it seems unwise to change course in midstream by shifting the definition. This is especially true because there is still no known precise pathophysiological feature that defines sepsis. 2.Abandoning the use of SIRS to focus on findings that are more highly predictive of death could encourage waiting, rather than early, aggressive intervention. This is a mistake that we cannot make.3.To abandon one system of recognizing sepsis because it is imperfect and not yet in universal use for another system that is used even less seems unwise without prospective validation of the new systems utility. Chest 2016 Feb第十八页，共四十二页。脓毒症3.0ACCP反对反对(fndu)Sepsis 3.04. What patients need is that we continue to build on the momentum of the last two decades and that we not disrupt it by conflating change with progress. 5. Our principal concern is that the new definition de-emphasizes intervention at earlier stages of sepsis when the syndrome is actually at its most treatable. We believe that adopting a more restrictive definition that requires further progression along the sepsis pathway may delay intervention in this highly time-dependent condition, with additional risk to patients. Chest 2016 Feb第十九页，共四十二页。脓毒症3.0精准精准(jn zhn)医学下的医学下的Sepsis 3.0不足不足 “Definition” versus “Clinical Criteria”. (1)Sepsis researchers, both bench and clinical, should consider how their findings might validate or invalidate the new definition; (2)Clinicians should determine if the clinical criteria are useful in their own practices and consider what additional elements ought to be tested; (3)sooner rather than later. Critical care medicine 2016 May; 44(5):857-8.第二十页，共四十二页。脓毒症3.0 “Dependent and Independent Variables”. Sepsis = (life-threatening)(organ dysfunction)(dysregulated host response)(infection). (1) Dont assume that the sequence of events identified in the new definition reflects pathobiological reality, because no one really knows how things are ordered and connected; (2) Dont assume that the predominant abnormality in sepsis is immunologicalthat hypothesis has dominated both mechanistic and therapeutic investigation for over two decades, and has yet to bear fruit. Critical care medicine 2016 May; 44(5):857-8.精准医学(yxu)下的Sepsis 3.0不足第二十一页，共四十二页。脓毒症3.0精准医学精准医学(yxu)下的下的Sepsis 3.0不足不足 “Appropriate comparators”. (1)We need to reconsider just what constitutes an appropriate control for sepsis research; (2) At the very least, we ought to make sure that studies characterizing sepsis in animal models and in patients use similar controls. “What comes next? ”. Howand how soondo we initiate Sepsis-4.0? I dont knowbut lets not wait a decade and a half this time.Critical care medicine 2016 May; 44(5):857-8.第二十二页，共四十二页。脓毒症3.0第二十三页，共四十二页。脓毒症3.0 Problem #1: Sepsis-III remains subjectiveSepsis 3.0的的10个疑问个疑问(ywn)（一一）所有定义都包含所有定义都包含(bohn)了了“suspected infection”，但怎么，但怎么去界定去界定“suspected infection”却很难。却很难。第二十四页，共四十二页。脓毒症3.0 Problem #2: qSOFA & SOFA are mortality predictors, not tests for sepsisSepsis 3.0的的10个疑问个疑问(ywn)（二二）qSOFA & SOFA 评分(png fn)多用于死亡预测，而非用于检测sepsis。第二十五页，共四十二页。脓毒症3.0 Problem #3: Sepsis-III is less specific for infection than Sepsis-IISepsis 3.0的的10个疑问个疑问(ywn)（三三）Sepsis 3.0 对诊断(zhndun)感染特异性低于Sepsis 2.0 。第二十六页，共四十二页。脓毒症3.0 Problem #4: qSOFA has similar performance compared to SIRS for mortality predictionSepsis 3.0的的10个疑问个疑问(ywn)（四四）事实上，qSOFA与SIRS对死亡预测价值(jizh)相当 。第二十七页，共四十二页。脓毒症3.0 Problem #5: qSOFA may be less specific in diseases that directly cause hypotension, tachypnea, or deliriumSepsis 3.0的的10个疑问个疑问(ywn)（五五）第二十八页，共四十二页。脓毒症3.0Sepsis 3.0的的10个疑问个疑问(ywn)（六六） Problem #6: qSOFA is inconsistent with a validated prognostic model (CURB65)CURB65模型被认为肺炎(fiyn)诊断经典模型。qSOFA与之比较，会高估肺炎的死亡率。第二十九页，共四十二页。脓毒症3.0Sepsis 3.0的的10个疑问个疑问(ywn)（七七） Problem #7: Combining qSOFA and SOFA scores is not evidence-based among patients outside the ICUSOFA 比qSOFA特异性更低，似乎不符合(fh)逻辑。第三十页，共四十二页。脓毒症3.0Sepsis 3.0的的10个疑问个疑问(ywn)（八八） Problem #8: The combined performance of qSOFA + SOFA for mortality is not reported.第三十一页，共四十二页。脓毒症3.0Sepsis 3.0的的10个疑问个疑问(ywn)（九九）Problem #9: The overall sensitivity of Sepsis-III for sepsis might be 50% outside of the ICU第三十二页，共四十二页。脓毒症3.0Sepsis 3.0的的10个疑问个疑问(ywn)（十十）Problem #10: Sepsis-III is not a consensus guideline in the United States支持(zhch)团体：Society of Critical Care Medicinethe American Thoracic Societythe American Association of Critical Care Nurses暂未支持(zhch)团体：American College of Chest Physiciansthe Infectious Disease Society of America the Emergency Medicine societies the hospital medicine societies第三十三页，共四十二页。脓毒症3.0脓毒症未来(wili)发展机制(jzh)、诊治发展定义(dngy)更新：脓毒症3.0第三十四页，共四十二页。脓毒症3.0BMJ：Sepsis的病理生理的病理生理(shngl)及临床治疗及临床治疗 作者(zuzh)综述5000多篇文献（引文217篇），复习了近35年来脓毒症的流行病学，危险因素、微生物学以及病因学及其治疗的研究成果，。 综述对最新的Sepsis3.0也做了介绍和归纳，根据Sepsis3.0 定义规定，脓毒症是由于对感染的不适当的宿主反应而产生的危及生命的脏器功能障碍，而Sepsis1.0或2.0说的是全身炎症反应，两者的差别决定了其病理生理的机制是不一致的。BMJ (Clinical research ed.) 2016 353:i1585.第三十五页，共四十二页。脓毒症3.0BMJ:当前当前(dngqin)证据下的脓毒症诊治证据下的脓毒症诊治“取舍取舍”BMJ (Clinical research ed.) 2016 353:i1585.第三十六页，共四十二页。脓毒症3.0脓毒症未来发展脓毒症未来发展(fzhn)方向方向 What is the optimal fluid and vasopressor resuscitation strategy in the early phase of septic shock? 感染性休克早期阶段理想的液体与缩血管药物复苏策略？ Will lung protective ventilation in patients with sepsis reduce the development of acute respiratory distress syndrome? 肺保护通气降低SEPSIS患者ARDS发展？ Will new treatments reduce the incidence of acute kidney injury in patients with sepsis? 新疗法降低SEPSIS患者AKI发生率？发展方向发展方向 Can rapid, inexpensive, and specific microbiologic tests for defining causative pathogens be developed using genetic and other approaches? 快速(kui s)、廉价、特异的方法如基因检测等可行吗？ Will we develop new effective and safe antibiotics in an era of increasingly common drug resistant pathogens? 耐药时代的新抗菌药物？BMJ (Clinical research ed.) 2016 353:i1585.第三十七页，共四十二页。脓毒症3.0 How does the microbiome change in sepsis and how might this be leveraged therapeutically? SEPSIS中微生物如何变化及如何因此调整(tiozhng)治疗？ What are the long term physical, cognitive, and psychosocial changes in patients who survive sepsis, and can we develop effective rehabilitative techniques?SEPSIS存活者长期 的躯体、认知、心里有何变化？有效康复技术？ Can we improve the ability of preclinical models of sepsis to predict therapeutic efficacy? 改善SEPSIS临床前模型能力，预测治疗效果 Can we develop a range of point-of-care biomarkers to group patients with sepsis into pathophysiologic categories? This would improve our understanding of the biology and may enhance clinical trial design 能通过生物标志物对SEPSIS患者进行病理生理归类，从而加深认识提高临床研究的设计？ How will the recently released definitions and clinical criteria for sepsis shape its clinical detection, treatment, and research? 新标准对诊断、治疗、研究的影响？脓毒症未来脓毒症未来(wili)发展方向发展方向BMJ (Clinical research ed.) 2016 353:i1585.第三十八页，共四十二页。脓毒症3.0小小 结结 Sepsis 3.0支持者：支持者： 1. 较之旧定义，新定义简单明了，易于教学及理解； 2. qSOFA 专注于具有(jyu)提示意义的主要脏器系统的症状和体征； 3. qSOFA 已经回顾性的大数据分析证明可信有效； 4. qSOFA的敏感性与特异性优于既往的ICU环境之外应用的标准； 5. 新定义的发布及所引起的讨论有助于提高对该疾病的关注度。 Sepsis 3.0反对者：反对者： 1. 新定义强调的标准为“已知或疑似感染的患者”，但显然感染并非总能被发现，即使(jsh)使用血培养； 2. qSOFA 在非ICU环境的应用有可能过于敏感； 3. qSOFA与SOFA严格而言并非Sepsis的筛查工具，而应该是提示病死率增加的标志物； 4. 美国医疗保险中心（CMS）目前也尚未通过新的定义，而继续沿用Sepsis2.0； 5. 以上内容和定义不涉及第二科，换句话说，儿科目前缺乏相应应用。第三十九页，共四十二页。Clinical Infectious Diseases 2009; 48:000000Clinical Infectious Diseases 2009; 48:000000脓毒症3.03.0未来未来(wili)发发展展1、有待临床(ln chun)进一步论证2、SIRS是该“say baybay”吗？第四十页，共四十二页。脓毒症3.0谢谢 谢谢第四十一页，共四十二页。脓毒症3.0内容(nirng)总结孙仁华。结果发现，重症感染患者的绝对死亡率从 35.0% 下降到了 18.4%，总死亡率下降了 16.6%，年绝对死亡率下降了 1.3%，相对风险下降了 47.5%。然而该标准过于复杂，且缺乏充分的研究基础和科学研究证据支持，并未得到临床认可和应用。5. 以上(yshng)内容和定义不涉及第二科，换句话说，儿科目前缺乏相应应用第四十二页，共四十二页。