全身性感染與感染性休克

1、全身性感染與感染性休克全身性感染與感染性休克What is New?北京協(xié)和醫(yī)院杜斌全身性感染全身性感染(sepsis): 定義定義確證或可疑的感染, 以及某些下列指標(biāo)n一般指標(biāo)n炎癥指標(biāo)n血流動(dòng)力學(xué)指標(biāo)n器官功能不全指標(biāo)n組織灌注指標(biāo)Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, For the International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS I

2、nternational Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256全身性感染全身性感染(sepsis): 定義定義一般指標(biāo)發(fā)熱(核心體溫 38.3C)體溫過(guò)低(核心體溫 90 bpm或超過(guò)按年齡校正的正常值 2SD呼吸頻數(shù)神志改變明顯水腫或液體正平衡( 20 ml/kg/24 hr)無(wú)糖尿病患者出現(xiàn)高血糖( 120 mg/dl)炎癥指標(biāo)白細(xì)胞增加( 12 x 109/L)白細(xì)胞缺乏(10%血漿CRP超過(guò)正常值 2SD血漿PCT超過(guò)正常值 2SDLevy MM, Fink MP, Marshall JC, A

3、braham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, For the International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256全身性感染全身性感染(sepsis): 定義定義血流動(dòng)力學(xué)指標(biāo)低血壓(SBP 90 mmHg, MAP 40 mmHg)SvO2 3.5 L/mi

4、n/m2器官功能不全指標(biāo)低氧血癥(PaO2/FiO2 300)急性少尿( 0.5 mg/dl凝血障礙(INR 1.5或aPTT 60 sec)腸梗阻(無(wú)腸鳴音)血小板缺乏( 4 mg/dl或70 mmol/L)組織灌注指標(biāo)高乳酸血癥( 1 mmol/L)毛細(xì)血管充盈差或皮膚花斑Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, For the International Sepsis Definitions Conference. 2001 SCCM

5、/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256全身性感染全身性感染(sepsis): 改變定義的原因改變定義的原因診斷標(biāo)準(zhǔn)應(yīng)當(dāng)普遍適用于臨床醫(yī)療及臨床試驗(yàn)具有較高的敏感性和特異性避免過(guò)于復(fù)雜以至難以記憶或應(yīng)用采用普遍應(yīng)用的試驗(yàn)指標(biāo)適用于成人, 兒童和新生兒Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G

6、, For the International Sepsis Definitions Conference. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256全身性感染全身性感染(sepsis): 流行病學(xué)流行病學(xué)Martin GS, Mannino DM, Stephanie Eaton S, et al. The Epidemiology of Sepsis in the United States from 1979 thr

7、ough 2000. N Engl J Med 2003; 348: 1546-54.全身性感染全身性感染(sepsis): 流行病學(xué)流行病學(xué)致病菌革蘭陽(yáng)性菌n平均每年增加26.3%真菌n1979年5,231例n2000年16,042例n增加207%Martin GS, Mannino DM, Stephanie Eaton S, et al. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348: 1546-54.全身性感染全身性感染(sepsis): 流行

8、病學(xué)流行病學(xué)Martin GS, Mannino DM, Stephanie Eaton S, et al. The Epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348: 1546-54.全身性感染流行病學(xué)全身性感染流行病學(xué): USA 1979 2000ICD-9有關(guān)全身性感染的編碼500家急性病醫(yī)院750,000,000住院患者10,319,418例全身性感染/22年全身性感染發(fā)病率的推算全身性感染發(fā)病率的推算751,000773,875796,750819,62

9、5842,500865,375888,250911,125934,000200220032004200520062007200820092010平均每年增加1.5%; 相當(dāng)于年增新發(fā)病例約22,875例Angus DC, et al. The epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care.全身性感染臨床試驗(yàn)對(duì)照組的病死率全身性感染臨床試驗(yàn)對(duì)照組的病死率全身性感染與嚴(yán)重全身性感染全身性感染與嚴(yán)重全身性感染國(guó)家年份發(fā)病率死

10、亡率病死率費(fèi)用全身性感染USA197982.721.926.5%USA2000240.443.918.3%嚴(yán)重全身性感染USA19953000.8628.6%22100UK1997512447%3801 17963Australia20037737.5%嚴(yán)重全身性感染嚴(yán)重全身性感染: 與常見病的比較與常見病的比較Incidence of Severe Sepsis050100150200250300350AIDSColonCancerBreastCancerCHFSevereSepsisCase/100,000National Center for Health Statistics, 200

11、1. American Cancer Society, 2001. *American Heart Association. 2000. Angus DC et al. Crit Care Med. 2001 (In Press). Deaths of Severe Sepsis050000100000150000200000250000AIDSBreastCancerAMISevereSepsisDeaths/Year嚴(yán)重全身性感染與其他死因嚴(yán)重全身性感染與其他死因2001年死亡人數(shù)年死亡人數(shù)心血管疾病心血管疾病931,108惡性腫瘤惡性腫瘤553,768嚴(yán)重全身性感染嚴(yán)重全身性感染215,

12、000意外意外101,537Alzeimer氏病氏病53,852HIV/AIDS14,175全身性感染的醫(yī)療費(fèi)用全身性感染的醫(yī)療費(fèi)用2000年ICU醫(yī)療費(fèi)用的40%歐洲每年花費(fèi)7,600,000,0001美國(guó)每年花費(fèi)$16,700,000,0002Davies A et al. Abstract 581. 14th Annual Congress of the European Society of Intensive Care Medicine, Geneva, Switzerland, 30 September-3 October 2001Angus DC, Linde-Zwirble W

13、T, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:13031310Surviving Sepsis Campaign: Why?過(guò)去5年間陽(yáng)性結(jié)果的干預(yù)措施n嚴(yán)重全身性感染與感染性休克uEGDTu激素uAPCu小潮氣量通氣策略n危重病患者的一般治療u鎮(zhèn)靜u嚴(yán)格血糖控制u脫機(jī)方案嚴(yán)重全身性感染嚴(yán)重全身性感染 循證醫(yī)學(xué)指南循證醫(yī)學(xué)指南

14、干預(yù)措施NNT小潮氣量通氣策略11早期目標(biāo)指導(dǎo)治療6 8活化蛋白C16 (whole trial)8 (APACHE II 25)強(qiáng)化胰島素治療29ACTH刺激試驗(yàn)無(wú)反應(yīng)者小劑量激素治療7Surviving Sepsis Campaign (SSC) Guidelines for Management of Severe Sepsis and Septic ShockDellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM,

15、Ramsay G, Zimmerman JL, Vincent JL, Levy MM and the SSC Management Guidelines CommitteeCrit Care Med 2004; 32: 858-873Intensive Care Med 2004; 30: 536-555available online atThe guidelines were published in both Critical Care Medicine and inIntensive care Medicine, and are available on-lineSurviving

16、Sepsis CampaignGuidelines For Management OfSevere Sepsis / Septic ShockThe First RevisionA Preliminary ReportSurviving Sepsis Campaign Guideline最初復(fù)蘇(initial resuscitation)診斷(diagnosis)抗生素治療(antibiotic therapy)感染源控制(source control)液體治療(fluid therapy)升壓藥物(vasopressors)強(qiáng)心藥物(inotropic therapy)激素(steroid

17、s)活化蛋白C (recombinant human activated protein C)血液制品(blood product administration)ARDS機(jī)械通氣(mechanical ventilation of sepsis-induced ALI/ARDS)鎮(zhèn)靜(sedation, analgesia, and NMB in sepsis)血糖控制(glucose control)腎臟替代(renal replacement)碳酸氫鈉(bicarbonate therapy)DVT預(yù)防(DVT prophylaxis)應(yīng)激性潰瘍預(yù)防(stress ulcer prophy

18、laxis)考慮限制支持治療水平(consideration for limitation of support)Surviving Sepsis Campaign Guideline最初復(fù)蘇(initial resuscitation)診斷(diagnosis)抗生素治療(antibiotic therapy)感染源控制(source control)液體治療(fluid therapy)升壓藥物(vasopressors)強(qiáng)心藥物(inotropic therapy)激素(steroids)活化蛋白C (recombinant human activated protein C)血液制品(

19、blood product administration)ARDS機(jī)械通氣(mechanical ventilation of sepsis-induced ALI/ARDS)鎮(zhèn)靜(sedation, analgesia, and NMB in sepsis)血糖控制(glucose control)腎臟替代(renal replacement)碳酸氫鈉(bicarbonate therapy)DVT預(yù)防(DVT prophylaxis)應(yīng)激性潰瘍預(yù)防(stress ulcer prophylaxis)考慮限制支持治療水平(consideration for limitation of sup

20、port)推薦意見的評(píng)級(jí)系統(tǒng)推薦意見的評(píng)級(jí)系統(tǒng)推薦級(jí)別至少兩項(xiàng)I級(jí)研究支持一項(xiàng)I級(jí)研究支持僅有II級(jí)研究支持至少一項(xiàng)III級(jí)研究支持IV或V級(jí)研究支持證據(jù)級(jí)別結(jié)果明確的大規(guī)模隨機(jī)臨床試驗(yàn); 假陽(yáng)性或假陰性錯(cuò)誤危險(xiǎn)小結(jié)果不確定的小規(guī)模隨機(jī)臨床試驗(yàn); 假陽(yáng)性或假陰性錯(cuò)誤危險(xiǎn)中等非隨機(jī)同期對(duì)照非隨機(jī)歷史對(duì)照及專家意見病例報(bào)告, 非對(duì)照研究及專家意見Sackett DL. Chest 1989; 95: 2S-4SSprung CL, Bernard GR, Dellinger RP. Intensive Care Med 2001; 27(Suppl): S1-S2推薦意見的評(píng)級(jí)系統(tǒng)推薦意見的評(píng)級(jí)系

21、統(tǒng) GRADE證據(jù)的質(zhì)量評(píng)估指標(biāo)n試驗(yàn)設(shè)計(jì)n一致性n直接性(對(duì)所研究的問(wèn)題)n偏倚的報(bào)告評(píng)估級(jí)別nA 高質(zhì)量nB 中等質(zhì)量nC 低質(zhì)量nD 極低質(zhì)量推薦的強(qiáng)度1: 強(qiáng)烈推薦n方法學(xué)缺陷較少n作用較大n副作用較少2: 一般推薦n方法學(xué)缺陷較多n評(píng)價(jià)不確切n作用較小n明顯增加危害, 工作負(fù)擔(dān), 醫(yī)療費(fèi)用Surviving Sepsis Campaign Guideline推薦意見推薦意見(n = 46)51154210510152025ABCDE最初的復(fù)蘇治療最初的復(fù)蘇治療發(fā)生全身性感染誘發(fā)的低血壓時(shí)n低血壓n乳酸酸中毒乳酸清除率與感染性休克預(yù)后乳酸清除率與感染性休克預(yù)后乳酸清除率乳酸清除率 =(

22、乳酸乳酸ED Presentation 乳酸乳酸Hour 6) x 100乳酸乳酸ED Presentation嚴(yán)重全身感染與感染性休克預(yù)后的獨(dú)立危險(xiǎn)因素嚴(yán)重全身感染與感染性休克預(yù)后的獨(dú)立危險(xiǎn)因素p = .04Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2

23、004; 32:1637-1642.隱性低灌注與創(chuàng)傷預(yù)后隱性低灌注與創(chuàng)傷預(yù)后The Golden Hour and the Silver Day入選標(biāo)準(zhǔn):n成年創(chuàng)傷患者n存活時(shí)間 24小時(shí)nISS 20n血流動(dòng)力學(xué)穩(wěn)定uSBP 100uHR 1 mL/kg/hn乳酸 2.5 mmol/L或其他灌注不足表現(xiàn)Blow O, Magliore L, Claridge J, Butler K, Young J. The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 H

24、ours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964隱性低灌注與創(chuàng)傷預(yù)后隱性低灌注與創(chuàng)傷預(yù)后Blow O, Magliore L, Claridge J, Butler K, Young J. The Golden Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964輸

25、注液體或血液制品輸注液體或血液制品Swan-Ganz, 動(dòng)脈插管動(dòng)脈插管, 腎臟劑量多巴胺腎臟劑量多巴胺將將PCWP提高到提高到12 15將將Hct提高到提高到30%升壓藥物升壓藥物(多巴酚丁胺多巴酚丁胺)心臟超聲檢查心臟超聲檢查隱性低灌注與創(chuàng)傷預(yù)后隱性低灌注與創(chuàng)傷預(yù)后1001001005700213616943500204060801001200-6 hr7-12 hr13-24 hr 24 hr% of Patients存活率存活率呼吸系統(tǒng)并發(fā)癥呼吸系統(tǒng)并發(fā)癥MOSFBlow O, Magliore L, Claridge J, Butler K, Young J. The Golden

26、Hour and the Silver Day: Detection and Correction of Occult Hypoperfusion within 24 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964全身性感染的診斷全身性感染的診斷適當(dāng)?shù)呐囵B(yǎng)至少留取2個(gè)血培養(yǎng)n1個(gè)外周血培養(yǎng)n每個(gè)留置 48 h的血管通路留取1個(gè)血培養(yǎng)(Grade D)抗生素治療前后血培養(yǎng)的陽(yáng)性率抗生素治療前后血培養(yǎng)的陽(yáng)性率139名患者名患者抗生素治療前抗生素治療前抗生素治療過(guò)程中抗生素治療過(guò)程中開始抗生素治療開始抗生素治療8

27、3名患者名患者(60%)血培養(yǎng)陰性或血培養(yǎng)陰性或分離出污染菌分離出污染菌0/83 (0%)分離到致病菌分離到致病菌56名患者名患者(40%)分離到致病菌分離到致病菌26/56 (45%)分離到致病菌分離到致病菌25名患者名患者(45%)分離到致分離到致病的葡萄球菌病的葡萄球菌19/25 (76%)分離到葡萄球菌分離到葡萄球菌14名患者名患者(25%)分離到致分離到致病的鏈球菌病的鏈球菌5/14 (36%)分離到鏈球菌分離到鏈球菌17名患者名患者(30%)分離到革分離到革蘭陰性桿菌蘭陰性桿菌2/17 (12%)分離到革蘭陰性桿菌分離到革蘭陰性桿菌1/139 (0.72%)分離到新的致病菌分離到新

28、的致病菌Grace CJ, Lieberman J, Pierce K, et al. Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy. Clin Infect Dis 2001; 32: 1651-5臨床意義臨床意義在開始抗生素治療最初72小時(shí)內(nèi), 連續(xù)進(jìn)行血培養(yǎng)的結(jié)果, 可以根據(jù)應(yīng)用抗生素前血培養(yǎng)的結(jié)果預(yù)測(cè)極少分離到新的致病菌醫(yī)生可以等待應(yīng)用抗生素前的血培養(yǎng)結(jié)果回報(bào)后, 再進(jìn)行新的血培養(yǎng)Grace CJ, Lieberman J, Pierce K, et

29、al. Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy. Clin Infect Dis 2001; 32: 1651-5抗生素治療抗生素治療確診嚴(yán)重全身性感染后1小時(shí)內(nèi)開始靜脈抗生素治療1C(Grade E)早期應(yīng)用抗生素與感染患者病死率早期應(yīng)用抗生素與感染患者病死率Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimic

30、robial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589-1596早期應(yīng)用抗生素與感染患者病死率早期應(yīng)用抗生素與感染患者病死率Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in hum

31、an septic shock. Crit Care Med 2006; 34: 1589-1596持續(xù)低血壓或乳酸持續(xù)低血壓或乳酸 4 mmol/L最初的復(fù)蘇治療最初的復(fù)蘇治療最初6小時(shí)內(nèi)達(dá)到的目標(biāo)CVP 8 12 mmHgMAP 65 mmHgUO 0.5 ml/kg/hrScvO2 70%1B(Grade B)感染性休克感染性休克: 灌注壓與組織灌注灌注壓與組織灌注MAP 65MAP 75MAP 85F/LT尿量(ml)49 1856 2143 13.60/.71毛細(xì)血管血流(ml/min/100 g)6.0 1.65.8 1.15.3 0.9.59/.55紅細(xì)胞速度(au)0.42 0

32、.060.44 0.160.42 0.06.74/.97PiCO2 (mmHg)41 247 246 2.11/.12Pa PiCO2 (mmHg)13 317 316 3.27/.40LeDoux, Astiz ME, Carpati CM, Rackow ED. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000; 28:2729-2732影響感染性休克預(yù)后的循環(huán)指標(biāo)影響感染性休克預(yù)后的循環(huán)指標(biāo)目的: 確定與預(yù)后相關(guān)的血流動(dòng)力學(xué)指標(biāo)的適當(dāng)閾值設(shè)計(jì): 回顧性隊(duì)列研究n199

33、9 2002年, 治療的最初48小時(shí), 分析6和48小時(shí)結(jié)果:n病死率33%n單因素分析及邏輯回歸分析u入院時(shí)的MAP和乳酸水平u48小時(shí)的MAP, SvO2 70%以及CVP平均值nMAP 65 mmHg, SvO2 70%uAUC最大Varpula M, Tallgren M, Saukkonen K, et al. Hemodynamic variables related to outcome in septic shock. Intensive Care Med 2005; 31(8): 1066-1071影響感染性休克預(yù)后的循環(huán)指標(biāo)影響感染性休克預(yù)后的循環(huán)指標(biāo)邏輯回歸ROC分析pE

34、xp(B)AUC95%CIMAP0.0131.1560.8410.761 0.921AUC SvO2 34 g/dl或上升 9 g/dln血漿皮質(zhì)醇 15 g/dl或上升 9 g/dl全身性感染全身性感染: 相對(duì)性腎上腺皮質(zhì)功能相對(duì)性腎上腺皮質(zhì)功能不全不全(RAI)相對(duì)性腎上腺皮質(zhì)功能不相對(duì)性腎上腺皮質(zhì)功能不全的患病率全的患病率(%)全身性感染或全身性感染或ALI-ARDS16.3 55.0感染性休克感染性休克39.4 66.7CORTICUS50相對(duì)性腎上腺皮質(zhì)功能不全與病死率相對(duì)性腎上腺皮質(zhì)功能不全與病死率T0時(shí)血漿皮質(zhì)醇(g/dl)max (g/dl)病死率 926%= 34 34 96

35、7% 34 982%Annane D, Sbille V, Troch G, et al.: A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000, 283:1038-1045感染性休克的激素替代治療感染性休克的激素替代治療入選標(biāo)準(zhǔn)明確的感染灶休克發(fā)生 3 hrsC或 90 bpmSBP 5 g/kg/min)或NE或EpiUO 0.5 ml/kg/hr x 1 hr或PaO2/FiO2 2 mm

36、ol/L機(jī)械通氣治療治療組n氫化可的松50 mg iv q6hn9-氟氫可的松50 g qd安慰劑組療程7天Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71.感染性休克的激素替代治療感染性休克的激素替代治療No. (%)指標(biāo)指標(biāo)安慰劑安慰劑激素激素校正校正OR (95%CI)P值值無(wú)

37、反應(yīng)者無(wú)反應(yīng)者患者數(shù)患者數(shù)11511428天病死率天病死率73 (63)60 (53)0.54 (0.31 0.97).04ICU病死率病死率81 (70)66 (58)0.50 (0.28 0.89).02住院病死率住院病死率83 (72)70 (61)0.53 (0.29 0.96).041年病死率年病死率88 (77)77 (68)0.57 (0.31 1.04).07反應(yīng)者反應(yīng)者患者數(shù)患者數(shù)343628天病死率天病死率18 (53)22 (61)0.97 (0.32 2.99).96ICU病死率病死率20 (59)24 (67)0.99 (0.31 3.16).99住院病死率住院病死率

38、20 (59)25 (69)1.20 (0.38 3.76).751年病死率年病死率24 (71)25 (69)0.70 (0.20 2.40).57Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71.感染性休克的激素替代治療感染性休克的激素替代治療病例數(shù)病例數(shù) (%)指標(biāo)指標(biāo)安慰劑安

39、慰劑激素激素校正校正OR (95%CI)P值值所有患者所有患者患者數(shù)患者數(shù)15014928天病死率天病死率91 (61)82 (55)0.65 (0.39 1.07).09ICU病死率病死率101 (68)90 (60)0.61 (0.37 1.02).06住院病死率住院病死率103 (69)95 (63)0.67 (0.40 1.12).121年病死率年病死率112 (75)102 (68)0.62 (0.36 1.05).08Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hy

40、drocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288: 862-71.感染性休克的激素替代治療感染性休克的激素替代治療Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:

41、862-71.激素與感染激素與感染: 尚待闡明的問(wèn)題尚待闡明的問(wèn)題患者選擇n嚴(yán)重感染 vs. 感染性休克用藥時(shí)機(jī)n發(fā)病 8小時(shí) vs. 72小時(shí)激素療程是否減量預(yù)后指標(biāo)n休克逆轉(zhuǎn) vs. 病死率激素驟?？墒辜?xì)胞因子增加激素驟?？墒辜?xì)胞因子增加Keh D, Boehnke T, Weber-Cartens S, et al. Immunologic and hemodynamic effects of low-dose hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover

42、 study. Am J Respir Crit Care Med. 2003;167:512-520重組人活化蛋白重組人活化蛋白C死亡高危nAPACHE II 25n感染誘發(fā)的多器官功能衰竭n感染性休克n感染誘發(fā)的ARDS無(wú)絕對(duì)禁忌癥權(quán)衡相對(duì)禁忌癥(Grade B)全身性感染全身性感染: 活化蛋白活化蛋白C30.8%24.7%0%10%20%30%40%Mortality (%)Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for

43、severe sepsis. N Engl J Med 2001; 344: 699-709.安慰劑安慰劑(n = 840)活化蛋白活化蛋白C(n = 850)絕對(duì)病死率下降6.1%主要分析結(jié)果主要分析結(jié)果雙尾雙尾P值值0.005校正后的相對(duì)危險(xiǎn)度降低校正后的相對(duì)危險(xiǎn)度降低19.4%存活比數(shù)增加存活比數(shù)增加38.1%全身性感染全身性感染: 活化蛋白活化蛋白CBernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsi

44、s. N Engl J Med 2001; 344: 699-709.APACHE II四分位與病死率四分位與病死率01020304050601st (3 - 19)2nd (20 - 24)3rd (25 - 29)4th (30 - 53)APACHE II QuartileMortality (Percentage)PlaceboDrotrecoginBernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsi

45、s. N Engl J Med 2001; 344: 699-709.26:3357:4958:48118:80衰竭臟器數(shù)目與病死率衰竭臟器數(shù)目與病死率010203040506012345Number of Organ Failing at EntryMortality (Percentage)PlaceboDrotrecoginBernard GR, Vincent JL, Laterre PF, et al. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of s

46、evere sepsis. Crit Care Med 2003; 31Suppl: S85-S90.全身性感染全身性感染: 活化蛋白活化蛋白CPROWESSnRandomized, double-blinded, placebo-controllednKnown or suspected infection, SIRS criteria 3; organ dysfunction 1n28-day mortality rate: 30.8% vs.24.7% (p = 0.005)ADDRESSnRandomized, double-blinded, placebo-controllednSe

47、vere sepsis, APACHE II 25, or single-organ failuren28-day mortality rate: 17.0% vs. 18.5% (p = 0.34)ENHANCEnSingle-arm, open-labelnKnown or suspected infection, SIRS criteria 3; organ dysfunction 1n28-day mortality rate: 25.3%全身性感染全身性感染: 活化蛋白活化蛋白CWiedermann CJ, Kaneider NC. A meta-analysis of contro

48、lled trials of recombinant human activated protein C therapy in patients with sepsis. BMC Emergency Medicine 2005; 5: 7全身性感染全身性感染: 活化蛋白活化蛋白CEichacker PQ, Danner RL, Suffredini AF, Cui X, Natanson C. Reassessing recombinant human activated protein C for sepsis: Time for a new randomized controlled tr

49、ial. Crit Care Med 2005; 33(10): 2426-2428全身性感染全身性感染: 活化蛋白活化蛋白CEichacker PQ, Danner RL, Suffredini AF, Cui X, Natanson C. Reassessing recombinant human activated protein C for sepsis: Time for a new randomized controlled trial. Crit Care Med 2005; 33(10): 2426-2428血糖控制血糖控制病情穩(wěn)定后血糖 150 mg/dL持續(xù)輸注胰島素和葡萄

50、糖監(jiān)測(cè)n最初每30 60分鐘n穩(wěn)定后q4h(Grade D)血糖控制血糖控制血糖控制非常重要n最初病情穩(wěn)定后n靜脈輸注胰島素1B目標(biāo)范圍?n血糖 150 mg/dL2Cn血糖控制方案2Cn葡萄糖熱卡及監(jiān)測(cè)1B外科患者的強(qiáng)化胰島素治療外科患者的強(qiáng)化胰島素治療高血糖與胰島素抵抗現(xiàn)象十分普遍伴有AMI的糖尿病患者, 控制血糖水平 215 mg/L, 長(zhǎng)期預(yù)后得以顯著改善1, 2van den Berghe等人對(duì)1548名危重病患者進(jìn)行了隨機(jī)對(duì)照試驗(yàn), 以評(píng)價(jià)強(qiáng)化胰島素治療及傳統(tǒng)血糖控制方法對(duì)危重病患者的影響3Malmberg K. BMJ1997; 314: 1512-5Malmberg K. Ci

51、rculation 1999; 99: 2626-2632Van den Berghe G, et al. N Engl J Med 2001; 345: 1359-1367外科患者的強(qiáng)化胰島素治療外科患者的強(qiáng)化胰島素治療試驗(yàn)設(shè)計(jì)入住外科ICU的機(jī)械通氣患者所有患者接受200 300 g葡萄糖/天入ICU當(dāng)日TPN總熱卡的60 80%為葡萄糖提供對(duì)照組: 控制血糖180 200 mg/dl治療組: 控制血糖80 110 mg/dlVan Den Berghe G, Wouters P, Weekers F, et al.: Intensive insulin therapy in the cr

52、itically ill patients. N Engl J Med 2001, 345:1359-1367外科患者的強(qiáng)化胰島素治療外科患者的強(qiáng)化胰島素治療至隨訪第12個(gè)月, 強(qiáng)化胰島素治療可以降低病死率3.4% (p 0.04)強(qiáng)化胰島素治療還可以n住院病死率 34%n血行性感染率 46%n需要腎臟替代治療的急性腎功能衰竭 41%n輸血的中位數(shù) 50%Van Den Berghe G, Wouters P, Weekers F, et al.: Intensive insulin therapy in the critically ill patients. N Engl J Med 20

53、01, 345:1359-1367危重病患者的強(qiáng)化胰島素治療危重病患者的強(qiáng)化胰島素治療平均血糖水平下降n152.3 vs. 130.7 mg/dL (P 2501.62 (1.01 2.60)Krinsleyn持續(xù)腎臟替代治療14Pittasn胰島素治療3.4 (1.9 6.3)n糖尿病史n全身性感染Sepsis Resuscitation Bundle(應(yīng)在最初應(yīng)在最初6小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)測(cè)定血清乳酸水平應(yīng)用抗生素前留取血培養(yǎng)入急診室3小時(shí)或入ICU1小時(shí)內(nèi)應(yīng)用抗生素低血壓和(或)乳酸 4 mmol/L (36 mg/dl)時(shí):最初應(yīng)用晶體液至少20 ml/kg(或等量的膠體液)最初液體

54、復(fù)蘇無(wú)效時(shí)應(yīng)用升壓藥物以維持MAP 65 mmHg經(jīng)過(guò)液體復(fù)蘇后仍持續(xù)低血壓(感染性休克)和(或)乳酸 4 mmol/L (36 mg/dl):使CVP 8 mmHg使ScvO2 70%Sepsis Resuscitation Bundle(應(yīng)在最初應(yīng)在最初6小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)B.測(cè)定血清乳酸水平D.應(yīng)用抗生素前留取血培養(yǎng)E.入急診室3小時(shí)或入ICU1小時(shí)內(nèi)應(yīng)用抗生素E.低血壓和(或)乳酸 4 mmol/L (36 mg/dl)時(shí):最初應(yīng)用晶體液至少20 ml/kg(或等量的膠體液)最初液體復(fù)蘇無(wú)效時(shí)應(yīng)用升壓藥物以維持MAP 65 mm HgB.經(jīng)過(guò)液體復(fù)蘇后仍持續(xù)低血壓(感染性休克)和(

55、或)乳酸 4 mmol/L (36 mg/dl):使CVP 8 mm Hg使ScvO2 70%Sepsis Management Bundle(應(yīng)在最初應(yīng)在最初24小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)對(duì)感染性休克患者根據(jù)ICU標(biāo)準(zhǔn)化規(guī)定應(yīng)用小劑量激素根據(jù)ICU標(biāo)準(zhǔn)化規(guī)定應(yīng)用活化蛋白C控制血糖水平正常值下限, 且 150 mg/dl (8.3 mmol/L)維持機(jī)械通氣患者吸氣平臺(tái)壓力 30 cmH2OSepsis Management Bundle(應(yīng)在最初應(yīng)在最初24小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)C. 對(duì)感染性休克患者根據(jù)ICU標(biāo)準(zhǔn)化規(guī)定應(yīng)用小劑量激素B. 根據(jù)ICU標(biāo)準(zhǔn)化規(guī)定應(yīng)用活化蛋白CD. 控制血糖水平正常

56、值下限, 且 150 mg/dl (8.3 mmol/L)B. 維持機(jī)械通氣患者吸氣平臺(tái)壓力 30 cmH2OSurviving Sepsis Campaign Initial ResultsReporting the Gap betweenPerception and PracticeWhat We Think We Dovs.What We Actually DoARDS保護(hù)性通氣策略保護(hù)性通氣策略 ARDSnet小潮氣量傳統(tǒng)潮氣量P值患者數(shù)387405NAVt (ml/kg)6.2 0.911.8 0.8 .05Pplat (cmH2O)25 733 9 .05PIP (cmH2O)32

57、 839 10 .05RR (bpm)29 716 6 .05MV (lpm)12.9 3.612.6 4.5NSPEEP (cmH2O)9.4 3.68.6 3.6 .05PaO2 / FiO2158 73176 76 .05PaO2 (mmHg)76 2377 19NSPaCO2 (mmHg)40 1035 8 .05pH7.38 0.087.41 0.07 .05The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional

58、 tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308ARDS保護(hù)性通氣策略保護(hù)性通氣策略 ARDSnet0%10%20%30%40%50%6 mL/kg12 mL/kgThe Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes

59、 for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響02.557.51012.515Day 1Day 3Day of ALI/ARDSALI/ARDS Patients Receiving Lung-Protective Ventilation (%)PrereleasePostreleasePostfeedbackRubenfeld GD, et al. Am J Respir Cr

60、it Care Med 2001; 163: A295研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響10.310.510.39.687.76.92222122131051015202530351996199719981999200020012002Median Vt (ml/kg)% of ARDS patients receiving 6 ml/kg VtBrower RG, et al. Am J Respir Crit Care Med 2004; 169(suppl): A256ARDS Network Paper Published NEJM實(shí)施保護(hù)性通氣策略的障礙