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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 bpmRR 20 bpmWCC 12,000/mm3or 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,Stephanie Eaton
2、 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 care.,全身性感染临床试验对照组的病死率,全身
3、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 Unite
4、d 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 Management of Severe Sepsis and Septic Shock,Dellinger RP,
5、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 Critic
6、al Care Medicine and inIntensive 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(fluid therapy)升压药物(vasopressors)强心药物(inotropic therapy)激素(steroids)活化蛋白C(recombinant human activated
7、 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 li
8、mitation 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
9、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),严重全身性感染与感染性休克的治疗,SIRS,Sepsis,Se
10、vere 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/dL2C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,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
11、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,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SB
12、P 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
13、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,Magl
14、iore 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
15、,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 Wh
16、o 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 Antibiot
17、ic 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,Sepsis,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 determina
18、nt of survival in human septic shock.Crit Care Med 2006;34:1589-1596,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 mmHgMAP 65 mmHgUO 0.5 ml/kg/hrScvO2 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-d
19、irected therapy in the 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,EGDT组患者输液更多,Rivers E,Nguyen B,Havstad S,e
20、t al.Early goal-directed therapy in 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
21、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,心血管猝死21%vs.10%P=0.02MODS22%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
22、权衡相对禁忌症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,抗生素治疗与感染灶控制,早期目标
23、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 septic shock.JAMA 2002;288:
24、862-71.,ACTH test8 hours,SEPTICSHOCK,placebo,HC 50 mg/6 hours+FC 50 mcg/day p.o.,N=150,N=149,28-daymortality,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 patients with septic shock.JAMA 2002;288:86
25、2-71.,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):使CVP 8 mmHg使ScvO2 70%,Sepsis Management Bundle(应在最初24小
26、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 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 N
27、etwork: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,Adhere to“Best Pr
28、actice”?,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,Brunkhors
29、t 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 an
30、d 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),Pronovost P,2005,EGDT in ED,Trzeciak S,Dellinger RP,Abate NL,Cowan RM,Stauss M,Kilgannon JH,Zanotti S,P
31、arrillo 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,EGDT in ED,Trzeciak S,Dellinger RP,Abate NL,Cowan RM,Stauss M,Kilgannon JH,Zanotti S,Parrillo JE.Translating Rese
32、arch 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,Sepsis 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(6
33、4%)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 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Bun
34、dle(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 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(6 hour)
35、,RR 2.12(1.20 3.76)P=0.01NNT=3.9,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 patients with severe sepsis:a prospective observational study.Critical Care 2005,9:R764-R770(DOI 10.1186/cc3909),Sepsis Bundle(24 hour),RR
36、 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-hour 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r
37、hAPC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 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),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,
