2012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?,严重全身性感染与感染性休克,非特异性损伤引 起的临床反应, 满足 2条标准: T 38C or 90 bpm RR 20 bpm WCC 12,000/mm3 or 10%杆状核,SIRS = systemic inflammatory response syndrome,SIRS及可疑或 明确的感染,Chest 1992;101:1644.,全身性感染 伴器官衰竭,顽固性低血压,SIRS,Sepsis,Severe Sepsis,Septic Shock,全身性感染(sepsis): 流行病学,Martin GS, Mannino DM, S

2、tephanie 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

3、care.,全身性感染临床试验对照组的病死率,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 2001 Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epi

4、demiology 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,Surviving Sepsis Campaign (SSC) Guidelines for Ma

5、nagement 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 Committee Crit Care Med 2004; 32: 858-873 Intensive Care Med 200

6、4; 30: 536-555 available online at www.sccm.org The guidelines were published in both Critical Care Medicine and in Intensive care Medicine, and are available on-line,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(

7、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)

8、 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)

9、 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(

10、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),严重全身性感染与感染性休克的治疗,SIRS,Sepsis,Severe Sepsis,Septic Shock,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,强化胰岛素治疗严格控制血糖,外科患者的强化胰岛素治疗,Van Den Berghe G, Wouters P, Weekers F, e

11、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

12、ally ill patients. N Engl J Med 2001, 345:1359-1367,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,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 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:

13、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 O

14、utcome 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 O

15、ccult 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

16、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

17、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,严重全身性感染与感染性休克的治疗,SIRS,Se

18、psis,Severe Sepsis,Septic Shock,抗生素治疗与感染灶控制,确诊严重全身性感染后1小时内开始静脉抗生素治疗 1C,强化胰岛素治疗严格控制血糖,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:

19、 1589-1596,严重全身性感染与感染性休克的治疗,SIRS,Sepsis,Severe Sepsis,Septic Shock,抗生素治疗与感染灶控制,早期目标指导治疗,持续低血压或乳酸 4 mmol/L 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,强化胰岛素治疗严格控制血糖,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 seps

20、is 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,EGDT组患者输液更多,Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy i

21、n the treatment of severe sepsis and septic 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

22、 al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345:1368-1377,心血管猝死 21% vs. 10% P = 0.02 MODS 22% vs. 16% P = 0.27,严重全身性感染与感染性休克的治疗,SIRS,Sepsis,Severe Sepsis,Septic Shock,抗生素治疗与感染灶控制,早期目标指导治疗,死亡高危: APACHE II 25 感染诱发的MOF 感染性休克 感染诱发的ARDS 无绝对禁忌症 权

23、衡相对禁忌症 B,活化蛋白C治疗,强化胰岛素治疗严格控制血糖,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%,严重全身性感染与感染性休克的治疗,SIRS,Sepsis,Severe Sepsis,Septic Shock,抗生

24、素治疗与感染灶控制,早期目标指导治疗,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天 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,活化蛋白C治疗,激素替代治疗,强化胰岛素治疗严格控制血糖,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 sep

25、tic shock. JAMA 2002; 288: 862-71.,ACTH test 8 hours,SEPTIC SHOCK,placebo,HC 50 mg/6 hours + FC 50 mcg/day p.o.,N = 150,N = 149,28-day mortality,7 days,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 pat

26、ients with septic shock. JAMA 2002; 288: 862-71.,P = 0.04,P = 0.96,严重全身性感染 循证医学指南,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

27、): 使CVP 8 mmHg 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,Surviving Sepsis Campaign Initial Results Reporting the Gap between Perception and Practice,What We Think We Do vs. What We Actua

28、lly 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,P = 0.007,研究结果的发表对日常工作并无影响,Rubenfeld GD, et

29、al. Am J Respir Crit Care Med 2001; 163: A295,P = 0.11,P = 0.02,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.

30、(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 Therapies Results of the German “Prevalence” Study,Bru

31、nkhorst 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% Reductio

32、n (NS),Pronovost P, 2005,EGDT in ED,Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S, Parrillo JE. Translating Research to Clinical Practice: A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest 2006; 129

33、: 225-232,EGDT in ED,Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S, Parrillo JE. Translating Research to Clinical Practice: A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest 2006; 129: 225-232,Sepsi

34、s Bundle,101名严重全身性感染患者符合6小时Bundle 普通病房: 90 (89%) 急诊科: 11 (11%),71名收入ICU 符合24小时Bundle: 69 (98%),43 (61%)转出ICU,28 (39%)死于ICU,35 (81%)存活,8 (19%)死亡,65 (64%)存活,36 (36%)死亡,Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in

35、patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909),Sepsis Bundle,符合6小时Bundle (n = 101),符合24小时Bundle (n = 69),52% (52/101),30% (21/69),依从率,Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour se

36、psis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909),Sepsis Bundle (6 hour),RR 2.12 (1.20 3.76) P = 0.01 NNT = 3.9,Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour a

37、nd 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909),Sepsis Bundle (24 hour),RR 1.76 (0.84 3.64) P = 0.16,Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-ho

38、ur and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Critical Care 2005, 9:R764-R770 (DOI 10.1186/cc3909),感染性休克,标准治疗程序(SOP) EGDT 强化胰岛素治疗 应激剂量激素 rhAPC 肺保护性通气策略 经验性抗生素治疗 感染灶控制,Kortgen A, Niederprm P, Bauer M. Implementation of an eviden

39、ce-based “standard operating procedure” and outcome in septic shock. Crit Care Med 2006 (in press),感染性休克,Kortgen A, Niederprm P, Bauer M. Implementation of an evidence-based “standard operating procedure” and outcome in septic shock. Crit Care Med 2006 (in press),感染性休克,Kortgen A, Niederprm P, Bauer M. Implementation of an evidence-based “standard operating procedure” and outcome in septic shock. Crit Care Med 2006 (in press),全身性感染与感染性休克,发病率逐年增加 病死率高居不下 多项临床试验结果令人鼓舞 EGDT 激素 APC 小潮气量通气策略 严格血糖控制 综合治疗措施可能改善预后,