全身性感染与感染性休克

1、全身性感染与感染性休克全身性感染与感染性休克What is New?北京协和医院杜斌全身性感染全身性感染(sepsis): 定义定义确证或可疑的感染, 以及某些下列指标n一般指标n炎症指标n血流动力学指标n器官功能不全指标n组织灌注指标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): 定义定义一般指标发热(核心体温 38.3C)体温过低(核心体温 90 bpm或超过按年龄校正的正常值 2SD呼吸频数神志改变明显水肿或液体正平衡( 20 ml/kg/24 hr)无糖尿病患者出现高血糖( 120 mg/dl)炎症指标白细胞增加( 12 x 109/L)白细胞缺乏(10%血浆CRP超过正常值 2SD血浆PCT超过正常值 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): 定义定义血流动力学指标低血压(SBP 90 mmHg, MAP 40 mmHg)SvO2 3.5 L/mi

4、n/m2器官功能不全指标低氧血症(PaO2/FiO2 300)急性少尿( 0.5 mg/dl凝血障碍(INR 1.5或aPTT 60 sec)肠梗阻(无肠鸣音)血小板缺乏( 4 mg/dl或70 mmol/L)组织灌注指标高乳酸血症( 1 mmol/L)毛细血管充盈差或皮肤花斑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): 改变定义的原因改变定义的原因诊断标准应当普遍适用于临床医疗及临床试验具有较高的敏感性和特异性避免过于复杂以至难以记忆或应用采用普遍应用的试验指标适用于成人, 儿童和新生儿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): 流行病学流行病学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): 流行病学流行病学致病菌革兰阳性菌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、病学流行病学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.全身性感染流行病学全身性感染流行病学: USA 1979 2000ICD-9有关全身性感染的编码500家急性病医院750,000,000住院患者10,319,418例全身性感染/22年全身性感染发病率的推算全身性感染发病率的推算751,000773,875796,750819,62

9、5842,500865,375888,250911,125934,000200220032004200520062007200820092010平均每年增加1.5%; 相当于年增新发病例约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.全身性感染临床试验对照组的病死率全身性感染临床试验对照组的病死率全身性感染与严重全身性感染全身性感染与严重全身性感染国家年份发病率死

10、亡率病死率费用全身性感染USA197982.721.926.5%USA2000240.443.918.3%严重全身性感染USA19953000.8628.6%22100UK1997512447%3801 17963Australia20037737.5%严重全身性感染严重全身性感染: 与常见病的比较与常见病的比较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严重全身性感染与其他死因严重全身性感染与其他死因2001年死亡人数年死亡人数心血管疾病心血管疾病931,108恶性肿瘤恶性肿瘤553,768严重全身性感染严重全身性感染215,

12、000意外意外101,537Alzeimer氏病氏病53,852HIV/AIDS14,175全身性感染的医疗费用全身性感染的医疗费用2000年ICU医疗费用的40%欧洲每年花费7,600,000,0001美国每年花费$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?过去5年间阳性结果的干预措施n严重全身性感染与感染性休克uEGDTu激素uAPCu小潮气量通气策略n危重病患者的一般治疗u镇静u严格血糖控制u脱机方案严重全身性感染严重全身性感染 循证医学指南循证医学指南

14、干预措施NNT小潮气量通气策略11早期目标指导治疗6 8活化蛋白C16 (whole trial)8 (APACHE II 25)强化胰岛素治疗29ACTH刺激试验无反应者小剂量激素治疗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最初复苏(initial resuscitation)诊断(diagnosis)抗生素治疗(antibiotic therapy)感染源控制(source control)液体治疗(fluid therapy)升压药物(vasopressors)强心药物(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机械通气(mechanical ventilation of sepsis-induced ALI/ARDS)镇静(sedation, analgesia, and NMB in sepsis)血糖控制(glucose control)肾脏替代(renal replacement)碳酸氢钠(bicarbonate therapy)DVT预防(DVT prophylaxis)应激性溃疡预防(stress ulcer prophy

18、laxis)考虑限制支持治疗水平(consideration for limitation of support)Surviving Sepsis Campaign Guideline最初复苏(initial resuscitation)诊断(diagnosis)抗生素治疗(antibiotic therapy)感染源控制(source control)液体治疗(fluid therapy)升压药物(vasopressors)强心药物(inotropic therapy)激素(steroids)活化蛋白C (recombinant human activated protein C)血液制品(

19、blood product administration)ARDS机械通气(mechanical ventilation of sepsis-induced ALI/ARDS)镇静(sedation, analgesia, and NMB in sepsis)血糖控制(glucose control)肾脏替代(renal replacement)碳酸氢钠(bicarbonate therapy)DVT预防(DVT prophylaxis)应激性溃疡预防(stress ulcer prophylaxis)考虑限制支持治疗水平(consideration for limitation of sup

20、port)推荐意见的评级系统推荐意见的评级系统推荐级别至少两项I级研究支持一项I级研究支持仅有II级研究支持至少一项III级研究支持IV或V级研究支持证据级别结果明确的大规模随机临床试验; 假阳性或假阴性错误危险小结果不确定的小规模随机临床试验; 假阳性或假阴性错误危险中等非随机同期对照非随机历史对照及专家意见病例报告, 非对照研究及专家意见Sackett DL. Chest 1989; 95: 2S-4SSprung CL, Bernard GR, Dellinger RP. Intensive Care Med 2001; 27(Suppl): S1-S2推荐意见的评级系统推荐意见的评级系

21、统 GRADE证据的质量评估指标n试验设计n一致性n直接性(对所研究的问题)n偏倚的报告评估级别nA 高质量nB 中等质量nC 低质量nD 极低质量推荐的强度1: 强烈推荐n方法学缺陷较少n作用较大n副作用较少2: 一般推荐n方法学缺陷较多n评价不确切n作用较小n明显增加危害, 工作负担, 医疗费用Surviving Sepsis Campaign Guideline推荐意见推荐意见(n = 46)51154210510152025ABCDE最初的复苏治疗最初的复苏治疗发生全身性感染诱发的低血压时n低血压n乳酸酸中毒乳酸清除率与感染性休克预后乳酸清除率与感染性休克预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严重全身感染与感染性休克预后的独立危险因素严重全身感染与感染性休克预后的独立危险因素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.隐性低灌注与创伤预后隐性低灌注与创伤预后The Golden Hour and the Silver Day入选标准:n成年创伤患者n存活时间 24小时nISS 20n血流动力学稳定uSBP 100uHR 1 mL/kg/hn乳酸 2.5 mmol/L或其他灌注不足表现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隐性低灌注与创伤预后隐性低灌注与创伤预后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输

25、注液体或血液制品输注液体或血液制品Swan-Ganz, 动脉插管动脉插管, 肾脏剂量多巴胺肾脏剂量多巴胺将将PCWP提高到提高到12 15将将Hct提高到提高到30%升压药物升压药物(多巴酚丁胺多巴酚丁胺)心脏超声检查心脏超声检查隐性低灌注与创伤预后隐性低灌注与创伤预后1001001005700213616943500204060801001200-6 hr7-12 hr13-24 hr 24 hr% of Patients存活率存活率呼吸系统并发症呼吸系统并发症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全身性感染的诊断全身性感染的诊断适当的培养至少留取2个血培养n1个外周血培养n每个留置 48 h的血管通路留取1个血培养(Grade D)抗生素治疗前后血培养的阳性率抗生素治疗前后血培养的阳性率139名患者名患者抗生素治疗前抗生素治疗前抗生素治疗过程中抗生素治疗过程中开始抗生素治疗开始抗生素治疗8

27、3名患者名患者(60%)血培养阴性或血培养阴性或分离出污染菌分离出污染菌0/83 (0%)分离到致病菌分离到致病菌56名患者名患者(40%)分离到致病菌分离到致病菌26/56 (45%)分离到致病菌分离到致病菌25名患者名患者(45%)分离到致分离到致病的葡萄球菌病的葡萄球菌19/25 (76%)分离到葡萄球菌分离到葡萄球菌14名患者名患者(25%)分离到致分离到致病的链球菌病的链球菌5/14 (36%)分离到链球菌分离到链球菌17名患者名患者(30%)分离到革分离到革兰阴性杆菌兰阴性杆菌2/17 (12%)分离到革兰阴性杆菌分离到革兰阴性杆菌1/139 (0.72%)分离到新的致病菌分离到新

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临床意义临床意义在开始抗生素治疗最初72小时内, 连续进行血培养的结果, 可以根据应用抗生素前血培养的结果预测极少分离到新的致病菌医生可以等待应用抗生素前的血培养结果回报后, 再进行新的血培养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抗生素治疗抗生素治疗确诊严重全身性感染后1小时内开始静脉抗生素治疗1C(Grade E)早期应用抗生素与感染患者病死率早期应用抗生素与感染患者病死率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早期应用抗生素与感染患者病死率早期应用抗生素与感染患者病死率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持续低血压或乳酸持续低血压或乳酸 4 mmol/L最初的复苏治疗最初的复苏治疗最初6小时内达到的目标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: 灌注压与组织灌注灌注压与组织灌注MAP 65MAP 75MAP 85F/LT尿量(ml)49 1856 2143 13.60/.71毛细血管血流(ml/min/100 g)6.0 1.65.8 1.15.3 0.9.59/.55红细胞速度(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影响感染性休克预后的循环指标影响感染性休克预后的循环指标目的: 确定与预后相关的血流动力学指标的适当阈值设计: 回顾性队列研究n199

33、9 2002年, 治疗的最初48小时, 分析6和48小时结果:n病死率33%n单因素分析及逻辑回归分析u入院时的MAP和乳酸水平u48小时的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影响感染性休克预后的循环指标影响感染性休克预后的循环指标逻辑回归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血浆皮质醇 15 g/dl或上升 9 g/dl全身性感染全身性感染: 相对性肾上腺皮质功能相对性肾上腺皮质功能不全不全(RAI)相对性肾上腺皮质功能不相对性肾上腺皮质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相对性肾上腺皮质功能不全与病死率相对性肾上腺皮质功能不全与病死率T0时血浆皮质醇(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疗感染性休克的激素替代治疗入选标准明确的感染灶休克发生 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机械通气治疗治疗组n氢化可的松50 mg iv q6hn9-氟氢可的松50 g qd安慰剂组疗程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疗感染性休克的激素替代治疗No. (%)指标指标安慰剂安慰剂激素激素校正校正OR (95%CI)P值值无

37、反应者无反应者患者数患者数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反应者反应者患者数患者数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疗感染性休克的激素替代治疗病例数病例数 (%)指标指标安慰剂安

39、慰剂激素激素校正校正OR (95%CI)P值值所有患者所有患者患者数患者数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疗感染性休克的激素替代治疗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.激素与感染激素与感染: 尚待阐明的问题尚待阐明的问题患者选择n严重感染 vs. 感染性休克用药时机n发病 8小时 vs. 72小时激素疗程是否减量预后指标n休克逆转 vs. 病死率激素骤停可使细胞因子增加激素骤停可使细胞因子增加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重组人活化蛋白重组人活化蛋白C死亡高危nAPACHE II 25n感染诱发的多器官功能衰竭n感染性休克n感染诱发的ARDS无绝对禁忌症权衡相对禁忌症(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.安慰剂安慰剂(n = 840)活化蛋白活化蛋白C(n = 850)绝对病死率下降6.1%主要分析结果主要分析结果双尾双尾P值值0.005校正后的相对危险度降低校正后的相对危险度降低19.4%存活比数增加存活比数增加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四分位与病死率四分位与病死率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衰竭脏器数目与病死率衰竭脏器数目与病死率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稳定后血糖 150 mg/dL持续输注胰岛素和葡萄

50、糖监测n最初每30 60分钟n稳定后q4h(Grade D)血糖控制血糖控制血糖控制非常重要n最初病情稳定后n静脉输注胰岛素1B目标范围?n血糖 150 mg/dL2Cn血糖控制方案2Cn葡萄糖热卡及监测1B外科患者的强化胰岛素治疗外科患者的强化胰岛素治疗高血糖与胰岛素抵抗现象十分普遍伴有AMI的糖尿病患者, 控制血糖水平 215 mg/L, 长期预后得以显著改善1, 2van den Berghe等人对1548名危重病患者进行了随机对照试验, 以评价强化胰岛素治疗及传统血糖控制方法对危重病患者的影响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外科患者的强化胰岛素治疗外科患者的强化胰岛素治疗试验设计入住外科ICU的机械通气患者所有患者接受200 300 g葡萄糖/天入ICU当日TPN总热卡的60 80%为葡萄糖提供对照组: 控制血糖180 200 mg/dl治疗组: 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外科患者的强化胰岛素治疗外科患者的强化胰岛素治疗至随访第12个月, 强化胰岛素治疗可以降低病死率3.4% (p 0.04)强化胰岛素治疗还可以n住院病死率 34%n血行性感染率 46%n需要肾脏替代治疗的急性肾功能衰竭 41%n输血的中位数 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危重病患者的强化胰岛素治疗危重病患者的强化胰岛素治疗平均血糖水平下降n152.3 vs. 130.7 mg/dL (P 2501.62 (1.01 2.60)Krinsleyn持续肾脏替代治疗14Pittasn胰岛素治疗3.4 (1.9 6.3)n糖尿病史n全身性感染Sepsis Resuscitation Bundle(应在最初应在最初6小时内达到小时内达到)测定血清乳酸水平应用抗生素前留取血培养入急诊室3小时或入ICU1小时内应用抗生素低血压和(或)乳酸 4 mmol/L (36 mg/dl)时:最初应用晶体液至少20 ml/kg(或等量的胶体液)最初液体

54、复苏无效时应用升压药物以维持MAP 65 mmHg经过液体复苏后仍持续低血压(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(应在最初应在最初6小时内达到小时内达到)B.测定血清乳酸水平D.应用抗生素前留取血培养E.入急诊室3小时或入ICU1小时内应用抗生素E.低血压和(或)乳酸 4 mmol/L (36 mg/dl)时:最初应用晶体液至少20 ml/kg(或等量的胶体液)最初液体复苏无效时应用升压药物以维持MAP 65 mm HgB.经过液体复苏后仍持续低血压(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(应在最初应在最初24小时内达到小时内达到)对感染性休克患者根据ICU标准化规定应用小剂量激素根据ICU标准化规定应用活化蛋白C控制血糖水平正常值下限, 且 150 mg/dl (8.3 mmol/L)维持机械通气患者吸气平台压力 30 cmH2OSepsis Management Bundle(应在最初应在最初24小时内达到小时内达到)C. 对感染性休克患者根据ICU标准化规定应用小剂量激素B. 根据ICU标准化规定应用活化蛋白CD. 控制血糖水平正常

56、值下限, 且 150 mg/dl (8.3 mmol/L)B. 维持机械通气患者吸气平台压力 30 cmH2OSurviving Sepsis Campaign Initial ResultsReporting the Gap betweenPerception and PracticeWhat We Think We Dovs.What We Actually DoARDS保护性通气策略保护性通气策略 ARDSnet小潮气量传统潮气量P值患者数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保护性通气策略保护性通气策略 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研究结果的发表对日常工作并无影响研究结果的发表对日常工作并无影响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研究结果的发表对日常工作并无影响研究结果的发表对日常工作并无影响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实施保护性通气策略的障碍