全身性感染与感染性休克.ppt

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1、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 Internation

2、al 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

3、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

4、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

5、/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%

6、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 S

7、tates 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

8、 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

9、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 2001 Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcom

10、e, 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

11、 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 Committee Crit Care Med 2004; 32: 858-873 Intensive Care Med 2004; 30: 536-555 available online at www.sccm.org The guideline

12、s were published in both Critical Care Medicine and in Intensive care Medicine, and are available on-line,Surviving Sepsis Campaign Guidelines For Management Of Severe Sepsis / Septic Shock,The First Revision A Preliminary Report,Surviving Sepsis Campaign Guideline,最初复苏(initial resuscitation) 诊断(dia

13、gnosis) 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

14、 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)

15、 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 cont

16、rol) 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-4S Sprung CL, Bernard GR, Dellinger RP. Intensive Care Med 2001; 27(Suppl): S1-S2,推荐意见的评级系统 GRA

17、DE,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 0.989 95%CI 0.978 0.9

18、99 p = .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

19、 血流动力学稳定 SBP 100 HR 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, Cl

20、aridge 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

21、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

22、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

23、. 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. Usefulnes

24、s 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 criti

25、cal 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:

26、 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 mmHg MAP 65 mmHg UO 0.5 ml/kg/hr ScvO2 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

27、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 70%以及CVP平均值 MAP 65 mmHg, SvO2 70% AUC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

28、循环指标,Varpula M, Tallgren M, Saukkonen K, et al. Hemodynamic variables related to outcome in septic shock. Intensive Care Med 2005; 31(8): 1066-1071,全身性感染: 早期目标指导治疗,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001,

29、 345:1368-1377,全身性感染: 早期目标指导治疗,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377,EGDT组患者输液更多,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and se

30、ptic shock. N Engl J Med 2001, 345:1368-1377,EGDT组输血及应用多巴酚丁胺更多,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377,EGDT与感染性休克的预后,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the

31、 treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377,全身性感染: 早期目标指导治疗,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377,感染性休克的激素替代治疗,应用氢化可的松200 300 mg/d, 分为3 4次给药或持续静脉输注, 疗程7

32、天 经过充分液体复苏治疗后仍需升压药物 (Grade C) 经过液体复苏和升压药物治疗低血压持续1小时 1B 充分液体复苏后仍需升压药物至少1小时 2C,全身性感染: 相对性肾上腺皮质功能不全(RAI),ACTH刺激试验 步骤 ACTH 250 g im或iv 用药后0, 30和60分钟测定血浆皮质醇水平 诊断标准 血浆皮质醇 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 prog

33、nostic 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 bpm SBP 5 g/kg/min)或NE或Epi UO 2 mmol/L 机械通气,治疗 治疗组 氢化可的松50 mg iv q6h 9-氟氢可的松50 g qd 安慰剂组 疗程 7天,Annane D, Sebille V, Charpentier C, e

34、t 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

35、 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. Eff

36、ect 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 hemodyn

37、amic 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

38、 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 En

39、gl 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 (a

40、ctivated) (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,PROWESS Randomized, double-blinded, placebo-controlled Known or suspected infection, SIRS criteria 3; organ dysfunction 1 28-day mortality rate: 30.8% vs.24.7% (p

41、= 0.005) ADDRESS Randomized, double-blinded, placebo-controlled Severe sepsis, APACHE II 25, or single-organ failure 28-day mortality rate: 17.0% vs. 18.5% (p = 0.34) ENHANCE Single-arm, open-label Known or suspected infection, SIRS criteria 3; organ dysfunction 1 28-day mortality rate: 25.3%,全身性感染:

42、 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

43、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)

44、: 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/dL 2C 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, 2 van 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,Ma

45、lmberg K. BMJ1997; 314: 1512-5 Malmberg K. Circulation 1999; 99: 2626-2632 Van 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, e

46、t 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 critic

47、ally 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 .001) 高血糖( 200 mg/dL)者减少56.3% 低血糖患者比例未增加 新发肾脏功能不全减少75% (P=.03) 需要输注红细胞的患者比例减少18.7% (P=.04) 住院病死率下降29.3% (P=.002),Krinsley JS. Effect of an intensive glucose management protocol on the mortality of cri

48、tically ill adult patients. Mayo Clin Proc. 2004;79:992-1000,内科患者的强化胰岛素治疗,van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive Insulin Therapy in the Medical ICU. N Engl J Med 2006; 354: 449-61,内科患者的强化胰岛素治疗,van den Berghe G,

49、 Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive Insulin Therapy in the Medical ICU. N Engl J Med 2006; 354: 449-61,内科患者的强化胰岛素治疗,van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R. Intensive Insulin Therapy in the Medical ICU. N Engl J Med 2006; 354: 449-61,强化胰岛素治疗: 荟萃分析(n = 35),短期病死率 所有患者 0.85 (0.75 0.97) 外科患者 0.58 (0.22

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