膿毒癥 ppt課件

1、孫仁華浙江省人民醫(yī)院ICU2016-10,膿毒癥3.0“面面觀”,嚴重膿毒癥及膿毒性休克流行病學,嚴重膿毒癥患者死亡風險為34%，膿毒性休克患者死亡風險為50%。,結果發(fā)現(xiàn)，重癥感染患者的絕對死亡率從 35.0% 下降到了 18.4%，總死亡率下降了 16.6%，年絕對死亡率下降了 1.3%，相對風險下降了 47.5%。,JAMA. 2014 Apr 2;311(13):1308-16.,膿毒癥定義變遷（1.0）,Sepsis 1.

2、0=感染＋SIRS,Chest 1992 Jun; 101(6):1644-55,膿毒癥定義變遷（2.0）,Intensive Care Med. 2003 Apr;29(4):530-8. Epub 2003 Mar 28.,Sepsis 2.0=感染＋SIRS會議提出了包括20余條臨床癥狀和體征評估指標構成的診斷標準，即Sepsis 2.0。然而該標準過于復雜，且缺乏充分的研究基礎和科學研究證據(jù)支持，并未得到臨床認可和應用。,Di

3、agnostic criteria for sepsis,,,,,,The PIRO system for staging sepsis,2012,SSC指南發(fā)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.,2008

4、,2004,膿毒癥診斷標準的“爭議”,方法：通過對2000 年至2013 年澳大利亞和新西蘭172 個重癥加強治療病房(ICU)近120 萬例患者的數(shù)據(jù)分析，根據(jù)是否滿足≥2條全身炎癥反應綜合征(SIRS)的診斷標準將感染伴器官功能障礙的患者分為SIRS 陽性和SIRS 陰性兩組。結果：在近11萬例感染伴器官功能障礙的患者中，87.9%為SIRS陽性，12.1%為SIRS 陰性，在14年內兩組患者的臨床特征和病死率變化相似。校正分析顯

5、示，患者病死率隨著滿足SIRS標準項目的增加呈線性增高。結論：該研究說明現(xiàn)有膿毒癥標準有可能遺漏約 1/8 的感染伴器官功能障礙患者，且該標準不能確定病死率增加的臨界點，這提示當前膿毒癥的篩查標準的特異性不佳。,N Engl J Med, 2015, 372 (17): 1629-1638.,Do we need a new definition of sepsis?,……the definition of septic sho

6、ck currently revolves around variable blood pressure and/or lactate levels, with loosely termed or undefined ‘a(chǎn)dequacy of fluid resuscitation’ and ‘persistent’ hypotension. Defining sepsis must, however, be an ongoing it

7、erative 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 seps

8、is 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.,膿毒癥的診斷標準于1991年發(fā)布（膿毒癥1.0）,但過于敏感，可

9、能導致膿毒癥的過度診斷和治療；2001年更新版（膿毒癥2.0）又過于復雜，未被廣泛應用。,,膿毒癥3.0….. 2016年……,Sepsis 3.0“應運而生”,JAMA. 2016 Feb 23;315(8):801-10｀,Sepsis 3.0定義,JAMA. 2016 Feb 23;315(8):801-10｀,Mortality 10%,Sepsis 3.0＝Inf

10、ection＋SOFA≥2,Sepsis 3.0診斷標準,JAMA. 2016 Feb 23;315(8):801-10,Septic shock 定義及診斷標準,JAMA. 2016 Feb 23;315(8):801-10,Mortality 40%,Septic shock=Sepsis+輸液無反應低血壓+使用縮血管藥物維持MAP≥65mmHg）+乳酸則＞2mmol/L。,Septic shock is a subset of s

11、epsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.,,膿毒癥3.0診斷流程,JAMA. 2016 Feb 23;315(8):801-10,Sepsis 3.0,ACCP反對Sepsis 3.0,1.Given that use

12、 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 th

13、at 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.

14、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 system’s utility.,Chest 20

15、16 Feb,ACCP反對Sepsis 3.0,4. 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 d

16、efinition 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 sep

17、sis pathway may delay intervention in this highly time-dependent condition, with additional risk to patients.,Chest 2016 Feb,精準醫(yī)學下的Sepsis 3.0不足,“Definition” versus “Clinical Criteria”. (1)Sepsis researchers, both bench

18、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 el

19、ements ought to be tested; (3)sooner rather than later.,Critical care medicine 2016 May; 44(5):857-8.,“Dependent and Independent Variables”. Sepsis = ?[(life-threatening)(organ dysfunction)(dysregulated host respons

20、e)(infection)]. (1) Don’t 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) Don’t assume that th

21、e predominant abnormality in sepsis is immunological–that 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):85

22、7-8.,精準醫(yī)學下的Sepsis 3.0不足,精準醫(yī)學下的Sepsis 3.0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

23、 characterizing sepsis in animal models and in patients use similar controls. “What comes next? ”. How?and how soon?do we initiate Sepsis-4.0? I don’t know?but let’s not wait a decade and a half this time.,Critica

24、l care medicine 2016 May; 44(5):857-8.,Problem #1: Sepsis-III remains subjective,Sepsis 3.0的10個疑問（一）,所有定義都包含了“suspected infection”，但怎么去界定“suspected infection”卻很難。,Problem #2: qSOFA & SOFA are mortality predictors, no

25、t tests for sepsis,Sepsis 3.0的10個疑問（二）,qSOFA & SOFA 評分多用于死亡預測，而非用于檢測sepsis。,Problem #3: Sepsis-III is less specific for infection than Sepsis-II,Sepsis 3.0的10個疑問（三）,Sepsis 3.0 對診斷感染特異性低于Sepsis 2.0 。,Problem #4: qSOFA

26、 has similar performance compared to SIRS for mortality prediction,Sepsis 3.0的10個疑問（四）,事實上，qSOFA與SIRS對死亡預測價值相當 。,Problem #5: qSOFA may be less specific in diseases that directly cause hypotension, tachypnea, or delirium

27、,Sepsis 3.0的10個疑問（五）,Sepsis 3.0的10個疑問（六）,Problem #6: qSOFA is inconsistent with a validated prognostic model (CURB65),CURB65模型被認為肺炎診斷經(jīng)典模型。qSOFA與之比較，會高估肺炎的死亡率。,Sepsis 3.0的10個疑問（七）,Problem #7: Combining qSOFA and SOFA scor

28、es is not evidence-based among patients outside the ICU,SOFA 比qSOFA特異性更低，似乎不符合邏輯。,Sepsis 3.0的10個疑問（八）,Problem #8: The combined performance of {qSOFA + SOFA} for mortality is not reported.,Sepsis 3.0的10個疑問（九）,Problem #9:

29、The overall sensitivity of Sepsis-III for sepsis might be <50% outside of the ICU,Sepsis 3.0的10個疑問（十）,Problem #10: Sepsis-III is not a consensus guideline in the United States,支持團體：Society of Critical Care Medicinet

30、he American Thoracic Societythe American Association of Critical Care Nurses,暫未支持團體：American College of Chest Physiciansthe Infectious Disease Society of America the Emergency Medicine societies the hospital medicine

31、 societies,膿毒癥未來發(fā)展,機制、診治發(fā)展……,定義更新：膿毒癥3.0……,BMJ：Sepsis的病理生理及臨床治療,作者綜述5000多篇文獻（引文217篇），復習了近35年來膿毒癥的流行病學，危險因素、微生物學以及病因學及其治療的研究成果，。綜述對最新的Sepsis3.0也做了介紹和歸納，根據(jù)Sepsis3.0 定義規(guī)定，膿毒癥是由于對感染的不適當?shù)乃拗鞣磻a(chǎn)生的危及生命的臟器功能障礙，而Sepsis1.0或2.0說的是

32、全身炎癥反應，兩者的差別決定了其病理生理的機制是不一致的。,BMJ (Clinical research ed.) 2016 353:i1585.,BMJ:當前證據(jù)下的膿毒癥診治“取舍”,BMJ (Clinical research ed.) 2016 353:i1585.,膿毒癥未來發(fā)展方向,What is the optimal fluid and vasopressor resuscitation strategy in the

33、early phase of septic shock?  感染性休克早期階段理想的液體與縮血管藥物復蘇策略？Will lung protective ventilation in patients with sepsis reduce the development of acute respiratory distress syndrome? 肺保護通氣降低SEPSIS患者ARDS發(fā)展？ Will new treatm

34、ents reduce the incidence of acute kidney injury in patients with sepsis? 新療法降低SEPSIS患者AKI發(fā)生率？發(fā)展方向Can rapid, inexpensive, and specific microbiologic tests for defining causative pathogens be developed using genetic and

35、other approaches? 快速、廉價、特異的方法如基因檢測等可行嗎？Will we develop new effective and safe antibiotics in an era of increasingly common drug resistant pathogens? 耐藥時代的新抗菌藥物？,BMJ (Clinical research ed.) 2016 353:i1585.,How does the m

36、icrobiome change in sepsis and how might this be leveraged therapeutically?  SEPSIS中微生物如何變化及如何因此調整治療？What are the long term physical, cognitive, and psychosocial changes in patients who survive sepsis, and can we d

37、evelop effective rehabilitative techniques?SEPSIS存活者長期 的軀體、認知、心里有何變化？有效康復技術？Can we improve the ability of preclinical models of sepsis to predict therapeutic efficacy? 改善SEPSIS臨床前模型能力，預測治療效果Can we develop a range of po

38、int-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 能通過生物標志物對SEPSIS患者進行病理生理歸類，從而加深認識提高臨床研究的設計？

39、How will the recently released definitions and clinical criteria for sepsis  shape its clinical detection, treatment, and research?  新標準對診斷、治療、研究的影響？,膿毒癥未來發(fā)展方向,BMJ (Clinical research ed.) 2016 353:i1585.,小 結,S

40、epsis 3.0支持者：1. 較之舊定義，新定義簡單明了，易于教學及理解；2. qSOFA 專注于具有提示意義的主要臟器系統(tǒng)的癥狀和體征；3. qSOFA 已經(jīng)回顧性的大數(shù)據(jù)分析證明可信有效；4. qSOFA的敏感性與特異性優(yōu)于既往的ICU環(huán)境之外應用的標準；5. 新定義的發(fā)布及所引起的討論有助于提高對該疾病的關注度。,Sepsis 3.0反對者：1. 新定義強調的標準為“已知或疑似感染的患者”，但顯然感染并非總能被發(fā)現(xiàn)，

41、即使使用血培養(yǎng)；2. qSOFA 在非ICU環(huán)境的應用有可能過于敏感；3. qSOFA與SOFA嚴格而言并非Sepsis的篩查工具，而應該是提示病死率增加的標志物； 4. 美國醫(yī)療保險中心（CMS）目前也尚未通過新的定義，而繼續(xù)沿用Sepsis2.0；5. 以上內容和定義不涉及第二科，換句話說，兒科目前缺乏相應應用。,,,3.0未來發(fā)展,1、有待臨床進一步論證2、SIRS是該“say baybay