全身性感染与感染性休克PPT课件

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(sepsis): 定义,确证或可疑的感染, 以及某些下列指标一般指标炎症指标血流动力学指标器官功能不全指标组织灌注指标,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 International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256,全身性感染(sepsis): 定义,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 International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256,全身性感染(sepsis): 定义,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 International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-1256,全身性感染(sepsis): 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, 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(sepsis): 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(sepsis): 流行病学,致病菌革兰阳性菌平均每年增加26.3%真菌1979年5,231例2000年16,042例增加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(sepsis): 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: USA 1979 2000,ICD-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,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,全身性感染与严重全身性感染,严重全身性感染: 与常见病的比较,National Center for Health Statistics, 2001. American Cancer Society, 2001. *American Heart Association. 2000. Angus DC et al. Crit Care Med. 2001 (In Press).,严重全身性感染与其他死因,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$16,700,000,0002,Davies 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 WT, 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; 29:13031310,Surviving Sepsis Campaign: Why?,过去5年间阳性结果的干预措施严重全身性感染与感染性休克EGDT激素APC小潮气量通气策略危重病患者的一般治疗镇静严格血糖控制脱机方案,严重全身性感染 循证医学指南,Surviving Sepsis Campaign (SSC) Guidelines for Management of Severe Sepsis and Septic Shock,Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, 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 The guidelines were published in both Critical Care Medicine and inIntensive care Medicine, and are available on-line,Surviving Sepsis CampaignGuidelines For Management OfSevere Sepsis / Septic Shock,The First RevisionA Preliminary Report,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(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 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(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 support),推荐意见的评级系统,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 GRADE,证据的质量评估指标试验设计一致性直接性(对所研究的问题)偏倚的报告评估级别A 高质量B 中等质量C 低质量D 极低质量,推荐的强度1: 强烈推荐方法学缺陷较少作用较大副作用较少2: 一般推荐方法学缺陷较多评价不确切作用较小明显增加危害, 工作负担, 医疗费用,Surviving Sepsis Campaign Guideline推荐意见(n = 46),最初的复苏治疗,发生全身性感染诱发的低血压时低血压乳酸酸中毒,乳酸清除率与感染性休克预后,严重全身感染与感染性休克预后的独立危险因素乳酸清除率OR 0.98995%CI 0.978 0.999p = .04,Nguyen 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 2004; 32:1637-1642.,隐性低灌注与创伤预后,The Golden Hour and the Silver Day入选标准:成年创伤患者存活时间 24小时ISS 20血流动力学稳定SBP 100HR 1 mL/kg/h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 Hours Improves Outcome from Major Trauma. J Trauma 1999; 47(5): 964,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,严重创伤患者两次LA 2.5,输注液体或血液制品,重复LA 2.5,Swan-Ganz, 动脉插管, 肾脏剂量多巴胺,将PCWP提高到12 15将Hct提高到30%,重复LA 2.5,升压药物(多巴酚丁胺)心脏超声检查,若LA仍 2.5,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,全身性感染的诊断,适当的培养至少留取2个血培养1个外周血培养每个留置 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,139名患者,抗生素治疗前,抗生素治疗过程中,开始抗生素治疗,83名患者(60%)血培养阴性或分离出污染菌,0/83 (0%)分离到致病菌,56名患者(40%)分离到致病菌,26/56 (45%)分离到致病菌,25名患者(45%)分离到致病的葡萄球菌,19/25 (76%)分离到葡萄球菌,14名患者(25%)分离到致病的链球菌,5/14 (36%)分离到链球菌,17名患者(30%)分离到革兰阴性杆菌,2/17 (12%)分离到革兰阴性杆菌,1/139 (0.72%)分离到新的致病菌,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,应用抗生素前进行血培养分离到致病菌的可能性增加2.2倍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 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,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,Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial 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,Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589-1596,持续低血压或乳酸 4 mmol/L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: 灌注压与组织灌注,LeDoux, 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,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1999 2002年, 治疗的最初48小时, 分析6和48小时结果:病死率33%单因素分析及逻辑回归分析入院时的MAP和乳酸水平48小时的MAP, SvO2 34 g/dl或上升 9 g/dl血浆皮质醇 15 g/dl或上升 9 g/dl,全身性感染: 相对性肾上腺皮质功能不全(RAI),相对性肾上腺皮质功能不全与病死率,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,入选标准明确的感染灶休克发生 38.3C或 90 bpmSBP 5 g/kg/min)或NE或EpiUO 2 mmol/L机械通气,治疗治疗组氢化可的松50 mg iv q6h9-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,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,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,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.,激素与感染: 尚待阐明的问题,患者选择严重感染 vs. 感染性休克用药时机发病 8小时 vs. 72小时激素疗程是否减量预后指标休克逆转 vs. 病死率,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 study. Am J Respir Crit Care Med. 2003;167:512-520,重组人活化蛋白C,死亡高危APACHE II 25感染诱发的多器官功能衰竭感染性休克感染诱发的ARDS无绝对禁忌症权衡相对禁忌症(Grade B),全身性感染: 活化蛋白C,Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709.,安慰剂(n = 840),活化蛋白C(n = 850),绝对病死率下降6.1%,全身性感染: 活化蛋白C,Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709.,APACHE II四分位与病死率,Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709.,26:33,57:49,58:48,118:80,衰竭脏器数目与病死率,Bernard GR, Vincent JL, Laterre PF, et al. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003; 31Suppl: S85-S90.,全身性感染: 活化蛋白C,PROWESSRandomized, double-blinded, placebo-controlledKnown or suspected infection, SIRS criteria 3; organ dysfunction 128-day mortality rate: 30.8% vs.24.7% (p = 0.005)ADDRESSRandomized, double-blinded, placebo-controlledSevere sepsis, APACHE II 25, or single-organ failure28-day mortality rate: 17.0% vs. 18.5% (p = 0.34)ENHANCESingle-arm, open-labelKnown or suspected infection, SIRS criteria 3; organ dysfunction 128-day mortality rate: 25.3%,全身性感染: 活化蛋白C,Wiedermann CJ, Kaneider NC. A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis. BMC Emergency Medicine 2005; 5: 7,全身性感染: 活化蛋白C,Eichacker 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,全身性感染: 活化蛋白C,Eichacker 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,病情稳定后血糖 150 mg/dL持续输注胰岛素和葡萄糖监测最初每30 60分钟稳定后q4h(Grade D),血糖控制,血糖控制非常重要最初病情稳定后静脉输注胰岛素1B目标范围?血糖 150 mg/dL2C血糖控制方案2C葡萄糖热卡及监测1B,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3,Malmberg K. BMJ1997; 314: 1512-5Malmberg K. Circulation 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,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/dl,Van Den Berghe G, Wouters P, Weekers F, et al.: Intensive insulin therapy in the critically ill patients. N Engl J Med 2001, 345:1359-1367,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住院病死率 34%血行性感染率 46%需要肾脏替代治疗的急性肾功能衰竭 41%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 2001, 345:1359-1367,危重病患者的强化胰岛素治疗,平均血糖水平下降152.3 vs. 130.7 mg/dL (P 2501.62 (1.01 2.60)Krinsley持续肾脏替代治疗14Pittas胰岛素治疗3.4 (1.9 6.3)糖尿病史全身性感染,Sepsis Resuscitation Bundle(应在最初6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6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(或)乳酸 4 mmol/L (36 mg/dl):使CVP 8 mm Hg使ScvO2 70%,Sepsis Management Bundle(应在最初24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 cmH2O,Sepsis Management Bundle(应在最初24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 cmH2O,Surviving Sepsis Campaign Initial ResultsReporting the Gap betweenPerception and Practice,What We Think We Dovs.What We Actually Do,ARDS保护性通气策略 ARDSnet,The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308,ARDS保护性通气策略 ARDSnet,The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301-1308,P = 0.007,研究结果的发表对日常工作并无影响,Rubenfeld GD, et al. Am J Respir Crit Care Med 2001; 163: A295,P = 0.11,P = 0.02,研究结果的发表对日常工作并无影响,Brower RG, et al. Am J Respir Crit Care Med 2004; 169(suppl): A256,ARDS Network Paper Published NEJM,实施保护性通气策略的障碍,Rubenfeld GD, Cooper C, Carter G, Thompson BT, Hudson LD. Barriers to providing lung-protective ventilation to patients with acute lung injury. Crit Care Med 2004; 32:1289 -1293,Adhere to “Best Practice”?,Do you use lung protective strategy in ventilating acute lung injury patients?,Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted),Adhere to “Best Practice”?,Results of Non-Scripted Care Processes,Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted),Supportive and Adjunctive TherapiesResults of the German “Prevalence” Study,Brunkhorst FM, et al, for the German Competence Network Sepsis SepNet. The gap between perception and practice of sepsis therapy. (submitted),为何循证治疗在ICU中应用并不普遍,缺乏相关知识医疗费用报销的限制, 繁忙的工作安排ICU医生的怀疑危重病领域众多的阴性试验结果对证据的主观选择临床惰性不能正确鉴别患者医疗资源的配置,VHA 19-ICU Sepsis Bundles,69% Reduction (p 0.001),36% Reduction (NS),Pronovos