1、感染性休克早期目标复苏治疗的几种观点（优选）感染性休克早期目标复苏治疗的几种观点补充氧补充氧气管插管和机械通气气管插管和机械通气EARLY GOAL-DIRECTED THERAPY,EGDT中心静脉或者动脉穿刺中心静脉或者动脉穿刺镇静，肌松（插管患者）镇静，肌松（插管患者）CVPCVPMAPMAPS SCVOCVO2 2达标达标收住院收住院晶体液晶体液胶体液胶体液血管活性药物血管活性药物输血后红细胞压输血后红细胞压积积30%30%肌力药物肌力药物8mmHg8mmHg65mmHg65mmHg90mmHg90mmHg70%70%70%70%70%70%YESYESNON Engl J Med 2
2、001;345:1368-77EGDT主要是针对sepsis或者septic shock血液动力学的优化8-12mmHg8-12mmHg6565或或90mmHg90mmHg70%70%N Engl J Med 2001;345:1368-77N Engl J Med 2001;345:1368-77EGDT的提出明显减少患者死亡率（从46.5%到30.5%）迅速的组织缺氧的纠正可改善生存率。住院天数从18.4天到14.6天，但无统计学差异 Early goal-directed therapy(EGDT)provides significant benefits with respect to
3、 outcome in patients with severe sepsis and septic shock.(N Engl J Med 2001;345:1368-77.)N Engl J Med 2001;345:1368-77N Engl J Med 2001;345:1368-77Paul J Young,FCICMdespite volume resuscitation or initial lactate 4 mmol/LThe ProMISe Investigations,N England J Med,2014,372:1301-1311EGDT主要是针对sepsis或者s
4、eptic shock血液动力学的优化EGDT，这个在“Bundle”中担当核心的主策略终于在强大的证据面前显示出裂痕。明显减少患者死亡率（从46.N Engl J Med 2001;345:1368-77基于规范的标准治疗组：446例The ProCESS Investigations,N England J Med,2014,370:1683-1693早期识别SEPSIS关键Bundle 带给我们什么？Our results complete the planned trio of studies of EGDT,all of which showed that EGDT was not
5、superior to usual care.针对本项研究有较多的疑问？N Engl J Med 2001;345:1368-77The addition of continuous ScvO2 monitoring and strict protocolization did not improve outcomes in the EGDT group.感染性休克早期目标复苏治疗的几种观点TO BE COMPLETED WITHIN 3 HOURS次要目标：静脉补液量，血管活性药物，输血，器官功能支持的评价Bundle 带给我们什么？针对本项研究有较多的疑问？整个研究未用盲法？穿刺时必须的吗
6、？输血必须吗？如此多的液体合适吗？为什么对照组的死亡率如此之高？为什么本研究是阳性结果而其他研究是阴性？。SURVIVING SEPSIS CAMPAIGN CARE BUNDLESTO BE COMPLETED WITHIN 3 HOURS Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30 mL/kg crystalloid for hypotension or lactat
7、e 4 mmol/LTO BE COMPLETED WITHIN 6 HOURS Apply vasopressors to maintain a mean arterial pressure(MAP)65 mm Hg despite volume resuscitation or initial lactate 4 mmol/L -Measure central venous pressure(CVP)*-Measure central venous oxygen saturation(ScvO2)*Remeasure lactate if initial lactate was eleva
8、ted*SURVIVING SEPSIS CAMPAIGN CARE BUNDLESEGDT是针对血液动力学的优化有关SEPSIS 的新的临床研究ProCESS-Protocolized Care for Early Septic Shock.ARISE-Australasian Resusitation In Sepsis EvaluationProMISe-Protocolised Management In Sepsis 项目项目研究研究地区地区起止时间起止时间纳入中纳入中心数心数纳入病例纳入病例场所场所样本例数样本例数美国美国3.2008-12.201331ED1341澳大澳大利亚利亚
9、10.2008-4.201451ED1588英国英国2.2011-7.201456ED,ICU1260ProCESS 多中心 N=1341，大样本 前瞻性随机对照研究 终点目标：60天死亡率，90天死亡率，1年死亡率，是否需要器官功能支持The ProCESS Investigations,N England J Med,2014,370:1683-169312701例患者最终纳入1341例研究分三组 EGDT组：439例 基于规范的标准治疗组：446例 普通治疗组：456例ProCESSThe ProCESS Investigations,N England J Med,2014,370:1
10、683-1693ProCESSThe ProCESS Investigations,N England J Med,2014,370:1683-1693ProCESSThe ProCESS Investigations,N England J Med,2014,370:1683-1693ProCESSThe ProCESS Investigations,N England J Med,2014,370:1683-1693ARISE 多中心 N=1588，大样本 前瞻性随机对照研究 终点目标：生存时间，住院期间的病死率，住院时间，是否需要器官功能支持The ARISE Investigation
11、s,N England J Med,2014,371:1496-1506ARISE3559例患者最终纳入1588例研究分组 EGDT组：792例 普通治疗组：796例The ARISE Investigations,N England J Med,2014,371:1496-1506N Engl J Med 2001;345:1368-77EGDT组：439例EGDT组：439例12701例患者最终纳入1341例作者们都明显高估了基线病死率（28天病死率）和预计的组间差异，导致纳入病例不足The ProMISe Investigations,N England J Med,2014,372:1
12、301-1311如何看待这三项研究的阴性结论EGDT，这个在“Bundle”中担当核心的主策略终于在强大的证据面前显示出裂痕。Apply vasopressors to maintain a mean arterial pressure(MAP)65 mm Hg感染性休克早期目标复苏治疗的几种观点寻找更适合的目标值（目标必须存在）9 In our study,NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achie
13、ved with EGDT in the earlier study for patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation.Paul J Young,FCICMThe ProCESS Investigations,N England J Med,2014,370:1683-1693The addition of continuous ScvO2 monitoring and strict prot
14、ocolization did not improve outcomes in the EGDT group.provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.SURVIVING SEPSIS CAMPAIGN CARE BUNDLES普通治疗组：796例TO BE COMPLETED WITHIN 3 HOURS-Measure central venous oxygen saturation(ScvO2)*The ARISE Invest
15、igations,N England J Med,2014,371:1496-1506ARISEThe ARISE Investigations,N England J Med,2014,371:1496-1506ARISEThe ARISE Investigations,N England J Med,2014,371:1496-1506ARISEARISEThe ARISE Investigations,N England J Med,2014,371:1496-1506ProMISe 多中心 N=1260，大样本 前瞻性随机对照研究 终点目标：90天死亡率 次要目标：静脉补液量，血管活性
16、药物，输血，器官功能支持的评价The ProMISe Investigations,N England J Med,2014,372:1301-1311ProMISe6192例患者最终纳入1260名患者研究分组 EGDT组630例 普通治疗组630例The ProMISe Investigations,N England J Med,2014,372:1301-1311The ProMISe Investigations,N England J Med,2014,372:1301-1311终点目标：生存时间，住院期间的病死率，住院时间，是否需要器官功能支持Measure lactate lev
17、el6天，但无统计学差异The addition of continuous ScvO2 monitoring and strict protocolization did not improve outcomes in the EGDT group.明显减少患者死亡率（从46.Director of the Intensive Care Research Programme,如何看待这三项研究的阴性结论输血后红细胞压积30%Paul J Young,FCICMLESS IS MORE?Bundle 带给我们什么？The ARISE Investigations,N England J Med
18、,2014,371:1496-1506针对本项研究有较多的疑问？provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.(N Engl J Med 2001;345:1368-77.EGDT主要是针对sepsis或者septic shock血液动力学的优化通过对171个ICU 101064例患者的回顾性调查发现澳大利亚和新西兰地区10余年间重症感染和感染性休克的住院病死率由35.The ProMISe Investigations,N Englan
19、d J Med,2014,372:1301-13119 In our study,NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achieved with EGDT in the earlier study for patients with septic shock who were identified early and received intravenous antibiotics and adequat
20、e fluid resuscitation.如何看待这三项研究的阴性结论The ProMISe Investigations,N England J Med,2014,372:1301-1311ProMISeThe ProMISe Investigations,N England J Med,2014,372:1301-1311ProMISe In conclusion,our results suggest that techniques used in usual resuscitation have evolved over the 15 years since the landmark
21、 study by Rivers et al.9 In our study,NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achieved with EGDT in the earlier study for patients with septic shock who were identified early and received intravenous antibiotics and adequate f
22、luid resuscitation.ProMISeThe addition of continuous ScvO2 monitoring and strict protocolization did not improve outcomes in the EGDT group.Our results complete the planned trio of studies of EGDT,all of which showed that EGDT was not superior to usual care.如何看待这三项研究的阴性结论多中心大样本随机对照试验前瞻性研究如何看待这三项研究的阴
23、性结论试验预计探查到的组间病死率差异的范围疾病的基线病死率等因素作者们都明显高估了基线病死率（28天病死率）和预计的组间差异，导致纳入病例不足Our results complete the planned trio of studies of EGDT,all of which showed that EGDT was not superior to usual care.The ProMISe Investigations,N England J Med,2014,372:1301-1311寻找更实用而有效的监测指标进行适时补充N Engl J Med 2001;345:1368-77终点
24、目标：60天死亡率，90天死亡率，1年死亡率，是否需要器官功能支持provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.通过对171个ICU 101064例患者的回顾性调查发现澳大利亚和新西兰地区10余年间重症感染和感染性休克的住院病死率由35.终点目标：生存时间，住院期间的病死率，住院时间，是否需要器官功能支持N Engl J Med 2001;345:1368-77N=1588，大样本6192例患者最终纳入1260名患者LESS IS MOR
25、E?广谱抗生素的应用降阶梯治疗-Measure central venous pressure(CVP)*Measure lactate levelN Engl J Med 2001;345:1368-77The ProMISe Investigations,N England J Med,2014,372:1301-1311基于规范的标准治疗组：446例Bundle 带给我们什么？65或90mmHg如何看待这三项研究的阴性结论EGDT，这个在“Bundle”中担当核心的主策略终于在强大的证据面前显示出裂痕。EGDT，我们还需要吗？剩下什么？剩下什么？早期识别SEPSIS关键广谱抗生素的应用降
26、阶梯治疗进行适当的容量复苏Bundle Bundle 带给我们什么？带给我们什么？通过对171个ICU 101064例患者的回顾性调查发现澳大利亚和新西兰地区10余年间重症感染和感染性休克的住院病死率由35.0%下降至18.4%Bundle Bundle 带给我们什么？带给我们什么？同样提示实施BUNDLE以来，重症感染和感染性休克的住院病死率在下降，存在统计学意义。当指南遭遇临床？总是在评价。常常会疑惑。偶尔很坚定。Paul J Young,FCICM Intensive Care Specialist,Wellington Hospital,New Zealand and Director
27、 of the Intensive Care Research Programme,Medical Research Institute of New Zealand,Wellington,New Zealand LESS IS MORE?The ProCESS Investigations,N England J Med,2014,370:1683-1693ARISE-Australasian Resusitation In Sepsis Evaluation如何看待这三项研究的阴性结论N=1341，大样本如何看待这三项研究的阴性结论The ARISE Investigations,N En
28、gland J Med,2014,371:1496-1506明显减少患者死亡率（从46.The ProMISe Investigations,N England J Med,2014,372:1301-131165或90mmHg12701例患者最终纳入1341例TO BE COMPLETED WITHIN 3 HOURSprovides significant benefits with respect to outcome in patients with severe sepsis and septic shock.通过对171个ICU 101064例患者的回顾性调查发现澳大利亚和新西兰地
29、区10余年间重症感染和感染性休克的住院病死率由35.迅速的组织缺氧的纠正可改善生存率。TO BE COMPLETED WITHIN 3 HOURS终点目标：生存时间，住院期间的病死率，住院时间，是否需要器官功能支持(N Engl J Med 2001;345:1368-77.Bundle 带给我们什么？次要目标：静脉补液量，血管活性药物，输血，器官功能支持的评价N=1260，大样本针对本项研究有较多的疑问？(N Engl J Med 2001;345:1368-77.针对本项研究有较多的疑问？通过对171个ICU 101064例患者的回顾性调查发现澳大利亚和新西兰地区10余年间重症感染和感染性
30、休克的住院病死率由35.Apply vasopressors to maintain a mean arterial pressure(MAP)65 mm Hg9 In our study,NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achieved with EGDT in the earlier study for patients with septic shock who were identified
31、early and received intravenous antibiotics and adequate fluid resuscitation.The ProMISe Investigations,N England J Med,2014,372:1301-1311Our results complete the planned trio of studies of EGDT,all of which showed that EGDT was not superior to usual care.N Engl J Med 2001;345:1368-77Bundle 带给我们什么？Di
32、rector of the Intensive Care Research Programme,普通治疗组630例The ARISE Investigations,N England J Med,2014,371:1496-1506The ARISE Investigations,N England J Med,2014,371:1496-1506如何看待这三项研究的阴性结论输血后红细胞压积30%TO BE COMPLETED WITHIN 3 HOURSEGDT是针对血液动力学的优化The ProCESS Investigations,N England J Med,2014,370:1683-1693The ARISE Investigations,N England J Med,2014,371:1496-1506Director of the Intensive Care Research Programme,我们需要做的？寻找更适合的目标值（目标必须存在）更加细化、标准化提高可操作性和依从性寻找更实用而有效的监测指标进行适时补充 也许它并不完美 但并不能否认它的价值和它的可塑性
