Bundle Strategies in Sepsis ： Where We Are_Chinese Journal of Respiratory and Critical Care Medicine

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HUANG Wei , WAN Xianyao

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脓毒症; 治疗

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　　 “拯救脓毒症运动（Surviving Sepsis Campaign，SSC）”是国际危重病医学界为提高脓毒症诊治水平、降低病死率而于2002年发起的全球性运动。随后，由多个国际学术组织暨国际专家组发起与组编的《严重脓毒症与脓毒症休克治疗指南》[1]及其修订版[2]（以下统称为“SSC指南”）分别于2004年和2008年颁布。指南以循证医学为依据，总结了早期目标指导治疗（EGDT）、强化血糖控制（TGC）、小剂量激素替代治疗、活性蛋白C（APC）治疗等治疗方案，其核心就是将各自独立的疗法整合为整体化的“集束化治疗策略（Bundle Strategy）”，以期最大限度地发挥综合治疗效应[3]。按照SSC的建议，集束化治疗策略包括脓毒症复苏集束化策略（Sepsis Resuscitation Bundle）和脓毒症治疗集束化策略（Sepsis Management Bundle）。前者要求在诊断严重脓毒症后的6 h内完成血乳酸测定、血培养、早期广谱抗菌药物应用和EGDT等6项治疗策略；后者则要求在24 h内完成由小剂量激素、APC、TGC和限制气道平台压构成的4项治疗策略[4]。显然，上述策略借鉴了创伤救治的“黄金6小时”和“白银24小时”的理念。
　　目前已有越来越多的研究证据支持集束化治疗策略在急诊和ICU的早期实施，并显示出病死率降低的趋势。但实际的情况是临床上对该策略的实施与执行严重不足，集束化治疗策略所代表的强化、优先、积极的治疗理念并未获得普遍的贯彻，进而影响到获得病死率显著降低的收益。另一方面，集束化治疗策略的各治疗要素也非完美，其所依据的相关临床试验存在着诸多不足甚至可疑之处，而单纯的疗法叠加是否真能发挥事半功倍的效果也值得考量。为此，本文就当前国际上的相关研究进展进行反思，以供同道参考。

Citation： HUANG Wei ,WAN Xianyao. Bundle Strategies in Sepsis ： Where We Are. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(2): 106-109. doi: Copy

1.	Dellinger RP，Carlet JM，Masur H，et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med，2004，32:858-873.
2.	Dellinger RP，Levy MM，Carlet JM，et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med，2008，34:17-60.
3.	刘大为. 严重感染和感染性休克的集束治疗策略. 中华外科杂志，2006，44:1178-1180.
4.	Townsend SR，Schorr C，Levy MM，et al. Reducing Mortality in Severe Sepsis: The Surviving Sepsis Campaign. Clin Chest Med，2008，29:721-733.
5.	Remick DG. Pathophysiology of sepsis. Am J Pathol，2007，170:1435-1444.
6.	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.
7.	Van den Berghe G，Wilmer A，Hermans G，et al. Intensive insulin therapy in the medical ICU. N Engl J Med，2006，354:449-461.
8.	Krinsley J. Glycemic Control in critically ill patients: Leuven and Beyond. Chest ，2007，132:268-278.
9.	Rivers E，Nguyen B，Havstad S. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med，2001，345:1368-1377.
10.	万献尧，黄伟. 对国际上有关全身性感染诊断标准与治疗指南的一些看法. 中华内科杂志，2007，46:709.
11.	Deans KJ, Minneci PC, Suffredini AF,et al. Randomization in clinical trials of titrated therapies: unintended consequences of using fixed treatment protocols. Crit Care Med，2007，35:1509-1516.
12.	Annane D，Sébille V，Charpentier C，et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA，2002，288:862-871.
13.	Sprung CL，Annane D，Keh D，et al. Hydrocortisone Therapy for Patients with Septic Shock. N Engl J Med，2008，358:111-124.
14.	Eichacker PQ，Natanson C，Danner RL. Surviving Sepsis: practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med，2006，355:1640-1642.
15.	Eichacker PQ，Natanson C. Increasing evidence that the risks of rhAPC may outweigh its benefits. Intensive Care Med，2007，33:396-399.
16.	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. The Acute Respiratory Distress Syndrome Network. N Engl J Med，2000，342:1301-1308.
17.	黄伟，万献尧. 急性肺损伤/急性呼吸窘迫综合征小潮气量通气策略的争议. 中国呼吸与危重监护杂志，2003，2:377-378.
18.	Brunkhorst FM，Engel C，Bloos F，et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med，2008，358:125-139.
19.	Gao F，Melody T，Daniels DF，et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care，2005，9:R764-R770.
20.	Douglas IS，Marchlowska P，Rains R，et al. A statewide implementation of surviving sepsis campaign bundles by the Colorado Critical Care Collaborative. Crit Care Med，2006，34:A99.
21.	Kortgen A，Niederprüm P，Bauer M. Implementation of an evidence-based standard operating procedure and outcome in septic shock. Crit Care Med，2006，34:943-949.
22.	Micek ST，Roubinian N，Heuring T，et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med，2006，34:2707-2713.
23.	Shapiro N， Howell MD，Bates DW，et al. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med，2006，48:583-590，590.e1.
24.	Nguyen HB，Corbett SW，Steele R，et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med，2007，35:1105-1112.
25.	Ferrer R，Artigas A，Levy MM，et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA，2008，299:2294-2303.
26.	Zambon M，Ceola M，Almeida-de-Castro R，et al. Implementation of the Surviving Sepsis Campaign guidelines for severe sepsis and septic shock: we could go faster. J Crit Care，2008，23:455-460.
27.	陈齐红，郑瑞强，林华，等. 感染性休克集束治疗对病死率影响的前瞻性研究. 中国危重病急救医学，2008，20:534-537.
28.	郭琦，黎敏毅，农凌波，等. 严重感染集束治疗的依从性研究. 中国危重病急救医学，2009，21:8-12.
29.	Kerr M. SCCM 2009: Sepsis Management "Bundles" Boost Guideline Implementation，Reduce Mortality. http://www.medscape.com/viewarticle/587759.
30.	Shorr AF，Micek ST，Jackson WL，et al. Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs？Crit Care Med，2007，35:1257-1262.
31.	Talmor D，Greenberg D，Howell MD，et al. The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med，2008，36:1168-1174.
32.	Brunkhorst FM，Engel C，Ragaller M，et al. Practice and perception—A nationwide survey of therapy habits in sepsis. Crit Care Med，2008，36:2719-2725.
33.	DuBose JJ，Inaba K，Shiflett A，et al. Measurable outcomes of quality improvement in the trauma intensive care unit: The Impact of a Daily Quality Rounding Checklist. J Trauma，2008，64:22-29.

1. Dellinger RP，Carlet JM，Masur H，et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med，2004，32:858-873.
2. Dellinger RP，Levy MM，Carlet JM，et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Intensive Care Med，2008，34:17-60.
3. 刘大为. 严重感染和感染性休克的集束治疗策略. 中华外科杂志，2006，44:1178-1180.
4. Townsend SR，Schorr C，Levy MM，et al. Reducing Mortality in Severe Sepsis: The Surviving Sepsis Campaign. Clin Chest Med，2008，29:721-733.
5. Remick DG. Pathophysiology of sepsis. Am J Pathol，2007，170:1435-1444.
6. 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.
7. Van den Berghe G，Wilmer A，Hermans G，et al. Intensive insulin therapy in the medical ICU. N Engl J Med，2006，354:449-461.
8. Krinsley J. Glycemic Control in critically ill patients: Leuven and Beyond. Chest ，2007，132:268-278.
9. Rivers E，Nguyen B，Havstad S. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med，2001，345:1368-1377.
10. 万献尧，黄伟. 对国际上有关全身性感染诊断标准与治疗指南的一些看法. 中华内科杂志，2007，46:709.
11. Deans KJ, Minneci PC, Suffredini AF,et al. Randomization in clinical trials of titrated therapies: unintended consequences of using fixed treatment protocols. Crit Care Med，2007，35:1509-1516.
12. Annane D，Sébille V，Charpentier C，et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA，2002，288:862-871.
13. Sprung CL，Annane D，Keh D，et al. Hydrocortisone Therapy for Patients with Septic Shock. N Engl J Med，2008，358:111-124.
14. Eichacker PQ，Natanson C，Danner RL. Surviving Sepsis: practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med，2006，355:1640-1642.
15. Eichacker PQ，Natanson C. Increasing evidence that the risks of rhAPC may outweigh its benefits. Intensive Care Med，2007，33:396-399.
16. 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. The Acute Respiratory Distress Syndrome Network. N Engl J Med，2000，342:1301-1308.
17. 黄伟，万献尧. 急性肺损伤/急性呼吸窘迫综合征小潮气量通气策略的争议. 中国呼吸与危重监护杂志，2003，2:377-378.
18. Brunkhorst FM，Engel C，Bloos F，et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med，2008，358:125-139.
19. Gao F，Melody T，Daniels DF，et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care，2005，9:R764-R770.
20. Douglas IS，Marchlowska P，Rains R，et al. A statewide implementation of surviving sepsis campaign bundles by the Colorado Critical Care Collaborative. Crit Care Med，2006，34:A99.
21. Kortgen A，Niederprüm P，Bauer M. Implementation of an evidence-based standard operating procedure and outcome in septic shock. Crit Care Med，2006，34:943-949.
22. Micek ST，Roubinian N，Heuring T，et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med，2006，34:2707-2713.
23. Shapiro N， Howell MD，Bates DW，et al. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med，2006，48:583-590，590.e1.
24. Nguyen HB，Corbett SW，Steele R，et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med，2007，35:1105-1112.
25. Ferrer R，Artigas A，Levy MM，et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA，2008，299:2294-2303.
26. Zambon M，Ceola M，Almeida-de-Castro R，et al. Implementation of the Surviving Sepsis Campaign guidelines for severe sepsis and septic shock: we could go faster. J Crit Care，2008，23:455-460.
27. 陈齐红，郑瑞强，林华，等. 感染性休克集束治疗对病死率影响的前瞻性研究. 中国危重病急救医学，2008，20:534-537.
28. 郭琦，黎敏毅，农凌波，等. 严重感染集束治疗的依从性研究. 中国危重病急救医学，2009，21:8-12.
29. Kerr M. SCCM 2009: Sepsis Management "Bundles" Boost Guideline Implementation，Reduce Mortality. http://www.medscape.com/viewarticle/587759.
30. Shorr AF，Micek ST，Jackson WL，et al. Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs？Crit Care Med，2007，35:1257-1262.
31. Talmor D，Greenberg D，Howell MD，et al. The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med，2008，36:1168-1174.
32. Brunkhorst FM，Engel C，Ragaller M，et al. Practice and perception—A nationwide survey of therapy habits in sepsis. Crit Care Med，2008，36:2719-2725.
33. DuBose JJ，Inaba K，Shiflett A，et al. Measurable outcomes of quality improvement in the trauma intensive care unit: The Impact of a Daily Quality Rounding Checklist. J Trauma，2008，64:22-29.

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