1、膿毒癥之前世今生南通市第三人民醫(yī)院 重癥醫(yī)學(xué)科田李均危重癥專科護(hù)士理論培訓(xùn) 2018-07-061膿毒癥辭源及演變2膿毒癥 3.0 3膿毒癥治療進(jìn)展4膿毒癥未來展望目錄 CONTENTS膿毒癥辭源Sepsis 腐爛，和疾病、死亡有關(guān)。希波克拉底前460年-前370年 膿毒癥辭源Sepsis 1.0 = infection + SIRSChest 1992 Jun; 101(6):1644-55創(chuàng)傷燒傷胰腺炎缺血SIRSsepsisSEVERESEPSIS細(xì)菌其他病毒原蟲真菌其他INFECTIONSepsis 1.0Sepsis 1.0非特異性損傷引起的臨床反應(yīng)，滿足 2條標(biāo)準(zhǔn): 體溫：T 38

2、C or 90 bpm呼吸： 20 bpm白細(xì)胞計數(shù)： 12,000/mm3 或 10%重癥膿毒癥:膿毒癥患者出現(xiàn)器官功能障礙膿毒癥:SIRS及可疑或明確的感染膿毒性休克:嚴(yán)重感染導(dǎo)致的循環(huán)衰竭，表現(xiàn)為經(jīng)充分液體復(fù)蘇仍不能糾正的組織低灌注和低血壓。Sepsis 2.0Intensive 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(biāo)構(gòu)成的診斷標(biāo)準(zhǔn)，即Sepsis 2.0。創(chuàng)傷燒傷胰腺炎缺血SIRSsepsisSEVERESEPSIS細(xì)菌其他病毒原蟲真菌其他INFEC

3、TIONSepsis 2.0明確或懷疑的感染，加上以下部分指標(biāo)一般指標(biāo)發(fā)熱(38.3)低體溫(體內(nèi)核心溫度90次/分或超過年齡校正后正常值的2個標(biāo)準(zhǔn)差以上呼吸急促意識改變嚴(yán)重水腫或液體正平衡(24 h內(nèi)20 ml/kg)高血糖血糖7.7 mmol/L(140 mg/dl，無糖尿病)炎癥指標(biāo)白細(xì)胞增多白細(xì)胞計數(shù)(WBC)12109/L白細(xì)胞減少(WBC10C-反應(yīng)蛋白超過正常值2倍標(biāo)準(zhǔn)差以上血漿降鈣素原超過正常值2倍標(biāo)準(zhǔn)差以上血流動力學(xué)指標(biāo)低血壓收縮壓(SBP)90 mm Hg，MAP70 mm Hg，或SBP下降超過年齡校正后正常值的2倍標(biāo)準(zhǔn)差以上器官功能障礙指標(biāo)動脈低氧血癥氧合指數(shù)(PaO2

4、/FiO2)300 mmHg急性少尿(足量液體復(fù)蘇，但尿量44.2mol/L(0.5 mg/dL)凝血功能異常國際標(biāo)準(zhǔn)化比值(INR)1.5或活化部分凝血活酶時間(APTT)60 s腸梗阻(腸鳴音消失)血小板減少血小板計數(shù)(PLT)70 mol/L(4mg/dL)組織灌注指標(biāo)高乳酸血癥(血乳酸1 mmol/L)毛細(xì)血管充盈受損或皮膚花斑該標(biāo)準(zhǔn)過于復(fù)雜，且缺乏充分的研究基礎(chǔ)和科學(xué)研究證據(jù)支持，并未得到臨床認(rèn)可和應(yīng)用！方法：通過對2000 年至2013 年澳大利亞和新西蘭172 個重癥加強(qiáng)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(yīng)綜合征(SIRS)的診斷標(biāo)準(zhǔn)將感染

5、伴器官功能障礙的患者分為SIRS 陽性和SIRS 陰性兩組。結(jié)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(nèi)兩組患者的臨床特征和病死率變化相似。校正分析顯示，患者病死率隨著滿足SIRS標(biāo)準(zhǔn)項目的增加呈線性增高。結(jié)論：該研究說明現(xiàn)有膿毒癥標(biāo)準(zhǔn)有可能遺漏約 1/8 的感染伴器官功能障礙患者，且該標(biāo)準(zhǔn)不能確定病死率增加的臨界點，這提示當(dāng)前膿毒癥的篩查標(biāo)準(zhǔn)的特異性不佳。 N Engl J Med, 2015, 372 (17): 1629-1638. 膿毒癥診斷標(biāo)準(zhǔn)的“爭議”Do we need a new definition of se

6、psis? 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

7、 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

8、of sepsis 4.0.Intensive Care Med, 2015, 41 (5): 909-911. 膿毒癥的診斷標(biāo)準(zhǔn)于1991年發(fā)布（膿毒癥1.0）,但過于敏感，可能導(dǎo)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(fù)雜，未被廣泛應(yīng)用。 Sepsis 3.0“應(yīng)運(yùn)而生”JAMA. 2016 Feb 23;315(8):801-101膿毒癥辭源及演變2膿毒癥 3.0 3膿毒癥治療進(jìn)展4膿毒癥未來展望目錄 CONTENTSSepsis 3.0定義JAMA. 2016 Feb 23;315(8):801-10感染引起的宿主異常反應(yīng)所導(dǎo)致的危及生命的多器官功能障礙。Sep

9、sis 3.0InfectionSOFA2Sepsis 3.0診斷標(biāo)準(zhǔn)JAMA. 2016 Feb 23;315(8):801-10Septic shock 定義及診斷標(biāo)準(zhǔn)JAMA. 2016 Feb 23;315(8):801-10Septic shock=Sepsis+輸液無反應(yīng)低血壓+使用縮血管藥物維持MAP65mmHg）+乳酸則2mmol/L。Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough

10、 to substantially increase mortality. 膿毒癥篩查膿毒癥3.0診斷流程JAMA. 2016 Feb 23;315(8):801-10Problem #1: Sepsis-III remains subjectiveSepsis 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, not tests for sepsisSepsis 3.0的10個疑問（二）qSOFA

11、 & SOFA 評分多用于死亡預(yù)測，而非用于檢測sepsis。Problem #3: Sepsis-III is less specific for infection than Sepsis-IISepsis 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 has similar performance compared to SIRS for mortality predictionSepsis 3.0的10個疑問（四）事實上，qSOFA與SIRS對死亡預(yù)測價值相當(dāng) 。Problem #5: qSOFA may

12、be less specific in diseases that directly cause hypotension, tachypnea, or deliriumSepsis 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(rèn)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 scores

13、 is not evidence-based among patients outside the ICUSOFA 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: The overall sensitivity of Sepsis-III for sepsis might be 0.5ml/kg/h、MAP65mmHg、CVP：812mmH

14、g、ScvO2或SvO270%或65%。 在血流動力學(xué)監(jiān)測下指導(dǎo)的液體復(fù)蘇血流動力學(xué)監(jiān)測手段包括壓力監(jiān)測、容量監(jiān)測及組織灌注監(jiān)測。 包括輸注不同液體（晶體、膠體），使用血管活性藥物或正性肌力藥物，以及提升血液攜氧能力的措施。液體復(fù)蘇時應(yīng)注意晶體液恢復(fù)生理需要量，微循環(huán)障礙的患者輸注人工膠體有望改善微循環(huán)灌注和預(yù)后，應(yīng)避免盲目使用白蛋白。 Early Goal-Directed Therapy: A house collapsing in slow motion殊途同歸CVP 8-12cmH20MAP65mmHgScvO270%尿量0.5ml/kg.h前負(fù)荷泵功能氧供/氧耗組織灌注EGDT是一種

15、理念，而非目標(biāo)不應(yīng)該強(qiáng)調(diào)數(shù)值，而應(yīng)該關(guān)心目的EGDT讓我們關(guān)心什么？1膿毒癥辭源及演變4膿毒癥未來展望2Sepsis 3.03膿毒癥治療進(jìn)展目錄 CONTENTSWhat is the optimal fluid and vasopressor resuscitation strategy in the 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(fù)蘇策略？Will lung protective ventilation in patients with sepsis reduce the development of acute resp

16、iratory distress syndrome? 肺保護(hù)通氣降低SEPSIS患者ARDS發(fā)展？ Will new treatments 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 other approaches

17、? 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.膿毒癥未來發(fā)展方向 How does the microbiome change in sepsis and how might this be leveraged therapeutically? SEPSIS中微生物如何變

18、化及如何因此調(diào)整治療？What are the long term physical, cognitive, and psychosocial changes in patients who survive sepsis, and can we develop effective rehabilitative techniques?SEPSIS存活者長期的軀體、認(rèn)知、心理有何變化？有效康復(fù)技術(shù)？Can we improve the ability of preclinical models of sepsis to predict therapeutic efficacy? 改善SEPSIS臨

19、床前模型能力，預(yù)測治療效果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 能通過生物標(biāo)志物對SEPSIS患者進(jìn)行病理生理歸類，從而加深認(rèn)識提高臨床研究的設(shè)計？How will the recently released definitions and clinical criteria for sepsis shape its clinical detec