再論膿毒癥的集束化治療策略_《中國呼吸與危重監護雜志》

作者：

黃偉 , 萬獻堯

大連醫科大學附屬一院重癥醫學科（遼寧大連 116011）;

關鍵詞：

膿毒癥治療

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　　 “拯救膿毒癥運動（Surviving Sepsis Campaign，SSC）”是國際危重病醫學界為提高膿毒癥診治水平、降低病死率而于2002年發起的全球性運動。隨后，由多個國際學術組織暨國際專家組發起與組編的《嚴重膿毒癥與膿毒癥休克治療指南》[1]及其修訂版[2]（以下統稱為“SSC指南”）分別于2004年和2008年頒布。指南以循證醫學為依據，總結了早期目標指導治療（EGDT）、強化血糖控制（TGC）、小劑量激素替代治療、活性蛋白C（APC）治療等治療方案，其核心就是將各自獨立的療法整合為整體化的“集束化治療策略（Bundle Strategy）”，以期最大限度地發揮綜合治療效應[3]。按照SSC的建議，集束化治療策略包括膿毒癥復蘇集束化策略（Sepsis Resuscitation Bundle）和膿毒癥治療集束化策略（Sepsis Management Bundle）。前者要求在診斷嚴重膿毒癥后的6 h內完成血乳酸測定、血培養、早期廣譜抗菌藥物應用和EGDT等6項治療策略；后者則要求在24 h內完成由小劑量激素、APC、TGC和限制氣道平臺壓構成的4項治療策略[4]。顯然，上述策略借鑒了創傷救治的“黃金6小時”和“白銀24小時”的理念。
　　目前已有越來越多的研究證據支持集束化治療策略在急診和ICU的早期實施，并顯示出病死率降低的趨勢。但實際的情況是臨床上對該策略的實施與執行嚴重不足，集束化治療策略所代表的強化、優先、積極的治療理念并未獲得普遍的貫徹，進而影響到獲得病死率顯著降低的收益。另一方面，集束化治療策略的各治療要素也非完美，其所依據的相關臨床試驗存在著諸多不足甚至可疑之處，而單純的療法疊加是否真能發揮事半功倍的效果也值得考量。為此，本文就當前國際上的相關研究進展進行反思，以供同道參考。

引用本文： 黃偉,萬獻堯. 再論膿毒癥的集束化治療策略. 中國呼吸與危重監護雜志, 2009, 09(2): 106-109. doi: 復制

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.	劉大為. 嚴重感染和感染性休克的集束治療策略. 中華外科雜志，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.	萬獻堯，黃偉. 對國際上有關全身性感染診斷標準與治療指南的一些看法. 中華內科雜志，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.	黃偉，萬獻堯. 急性肺損傷/急性呼吸窘迫綜合征小潮氣量通氣策略的爭議. 中國呼吸與危重監護雜志，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.	陳齊紅，鄭瑞強，林華，等. 感染性休克集束治療對病死率影響的前瞻性研究. 中國危重病急救醫學，2008，20:534-537.
28.	郭琦，黎敏毅，農凌波，等. 嚴重感染集束治療的依從性研究. 中國危重病急救醫學，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. 劉大為. 嚴重感染和感染性休克的集束治療策略. 中華外科雜志，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. 萬獻堯，黃偉. 對國際上有關全身性感染診斷標準與治療指南的一些看法. 中華內科雜志，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. 黃偉，萬獻堯. 急性肺損傷/急性呼吸窘迫綜合征小潮氣量通氣策略的爭議. 中國呼吸與危重監護雜志，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. 陳齊紅，鄭瑞強，林華，等. 感染性休克集束治療對病死率影響的前瞻性研究. 中國危重病急救醫學，2008，20:534-537.
28. 郭琦，黎敏毅，農凌波，等. 嚴重感染集束治療的依從性研究. 中國危重病急救醫學，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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