人類重組活化蛋白C治療嚴重膿毒癥的Meta分析_《中國循證醫學雜志》

作者：

王倩 ¹ , 趙陽 ² ,  朱杰 ¹

1. 中國醫科大學附屬第四醫院急診科（沈陽　110032）；2. 中國醫科大學附屬盛京醫院ICU（沈陽　110004）;

關鍵詞：

人類重組活化蛋白C 嚴重膿毒癥系統評價 Meta分析隨機對照試驗

DOI：

10.7507/1672-2531.20130229

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目的　系統評價人類重組活化蛋白C（rhAPC）治療嚴重膿毒癥的有效性及安全性。
方法　計算機檢索MEDLINE、EMbase、The Cochrane Library、VIP、CNKI、CBM和WanFang Data等數據庫，全面收集rhAPC治療嚴重膿毒癥的隨機對照試驗（RCT），檢索時限均為建庫至2012年7月，并追溯納入研究的參考文獻。由兩位研究者按照納入與排除標準獨立篩選文獻、提取資料和評價質量后，采用RevMan 5.0軟件進行Meta分析。
結果　共納入5個RCT，6 307例患者。Meta分析結果顯示：rhAPC組同安慰劑組相比，兩者在嚴重膿毒癥患者28天病死率［RR=1.00， 95%CI（0.84，1.19），P=1.00］和90天病死率［RR=1.00， 95%CI（0.87，1.14），P=0.96］方面差異均無統計學意義。對不同急性生理及慢性健康評分Ⅱ（Acute Physiology and Chronic Health EvaluationⅡ，APACHEⅡ）嚴重膿毒癥患者的28天病死率進行亞組分析，結果顯示兩組差異也無統計學意義［APACHEⅡ評分 lt;25分：RR=1.06，95%CI（0.93，1.21），P=0.37；APACHEⅡ評分≥25分：RR=0.93，95%CI（0.69，1.24），P=0.60］。不同活化蛋白C缺乏程度患者28天病死率的亞組分析結果顯示，兩組差異也無統計學意義［APC缺乏 lt;80%：RR=0.96，95%CI（0.56，1.65），P=0.89；APC缺乏 gt;80%：RR=0.61，95%CI（0.34，1.08），P=0.09］。此外，rhAPC能使嚴重膿毒癥患者嚴重出血事件發生的風險增加1.62倍［RR=1.62， 95%CI（1.17，2.23），P=0.004］，但兩組在嚴重不良反應總發生率方面，差異無統計學意義［RR=1.04， 95%CI（0.92，1.18），P=0.53］。
結論　現有證據表明，rhAPC并不能改善嚴重膿毒癥患者的預后，反而會增加出血風險。

引用本文： 王倩,趙陽,朱杰. 人類重組活化蛋白C治療嚴重膿毒癥的Meta分析. 中國循證醫學雜志, 2013, 13(11): 1333-1339. doi: 10.7507/1672-2531.20130229 復制

1.	Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med, 2003, 348(12): 1546-1554.
2.	Hall MJ, Williams SN, DeFrances CJ, et al. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief, 2011, (62): 1-8.
3.	Brun-Buisson C. Epidemiology of severe sepsis. Presse Médicale, 2006, 35(3 Pt 2): 513-520.
4.	Danai PA, Sinha S, Moss M, et al. Seasonal variation in the epidemiology of sepsis. Critical Care Medicine, 2007, 35(2): 410-415.
5.	Das UN. Critical advances in septicemia and septic shock. Criti Care, 2000, 4(5): 290-296.
6.	Khwannimit B, Bhurayanontachai R. The epidemiology of, and risk factors for, mortality from severe sepsis and septic shock in a tertiary-care university hospital setting. Epidemiology and Infection, 2009, 137(9): 1-9.
7.	Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care, 2004, 8(4): 222-226.?.
8.	Brun-Buisson C, Meshaka P, Pinton P, et al. EPISEPSIS: a reappraisal of the epidemiology and out- come of severe sepsis in French intensive care units. Intensive Care Med, 2004, 30(4): 580-588.
9.	Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001, 29(7): 1303-1313.
10.	Cheng B, Xie G, Yao S, et al. Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Critical Care Medicine, 2007, 35(11): 2538-2546.
11.	Paul M. Is there a treatment for sepsis other than antibiotics? Clinical Microbiology and Infection, 2009, 15(4): 297.
12.	Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med, 2003, 348(2): 138-150.
13.	Grey ST, Hancock WW. Inhibition of LPS-induced activation of human monocytes by activated protein C (APC) occurs through a novel mechanism. J Leukoc Biol, 1993, 114(6): A487.
14.	Bernard GR, Vincent JL, Laterre PF, et al, and the Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. E?cacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med, 2001, 344(5): 699-709.
15.	Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011, Available from: www.cochrane-handbook.org.
16.	Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
17.	Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ, 2003, 327()7414: 557-560.
18.	Egger M, Altman DG, Smith GD. Systematic reviews in health-care: meta-analysis in context. 2nd Ed. BMJ Books, Wiley: London, 2001.
19.	. Bernard GR, Ely EW, Wright TJ, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med, 2001, 29(11): 2051-2059.
20.	Angus DC, Laterre PF, Helterbrand J, et al, and PROWESS Investigators. The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis. Crit Care Med, 2004, 32(11): 2199-2206.
21.	Abraham E, Laterre PF, Garg R, et al, and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med, 2005, 353(13): 1332-1341.
22.	Dhainaut JF, Antonelli M, Wright P, et al. Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock. Intensive Care Med, 2009, 35(7): 1187-1195.
23.	Ranieri VM, Thompson BT, Barie PS, et al, and PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med, 2012, 366(22): 2055-2064.
24.	Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet, 2005, 365(9453): 63-78.
25.	Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood, 2007, 109(8): 3161-3172.
26.	Shorr AF, Bernard GR, Dhainaut JF, et al. Protein C concentrations in severe sepsis: An early directional change in plasma levels predicts outcome. Crit Care, 2006, 10(6): R92.
27.	MammenE. Thehaematological manifestations of sepsis. J Antimicrob Chemother, 1998, 41(Suppl A): S17-S24.
28.	Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med, 2008, 36(12): 296-327.
29.	Casserly B, Gerlach H, Phillips GS, et al. Evaluating the use of recombinant human activated protein C in adult severe sepsis: results of the Surviving Sepsis Campaign. Crit Care Med, 2012, 40(5): 1417-1426.
30.	Kalil AC, Larosa SP. Effectiveness and safety of drotrecogin alfa (activated) for severe sepsis: a meta-analysis and metaregression. Lancet Infect Dis, 2012, 12(9): 678-686.
31.	Rimmer E, Kumar A, Doucette S, et al, and Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Activated protein C and septic shock: A propensity-matched cohort study. Crit Care Med, 2012, 40(11): 2974-2981.
32.	Martí-Carvajal AJ, Solà I, Lathyris D, et al. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev, 2012, 3: CD004388.
33.	Nadel S, Goldstein B, Williams MD, et al, and Researching severe Sepsis and Organ dysfunction in children: a global perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet, 2007, 369(9564): 836-843.
34.	University of Versailles: Activated protein C and corticosteroids for human septic shock (APROCCHS). Available from: http://clinicaltrials.gov/ct2/show/NCT00625209. Accessed Oct 3, 2012.
35.	University of Versailles: Pharmacogenomic Biomarker Study for Recombinant Human Activated Protein C Treatment in Severe Sepsis. Available from: http://clinicaltrials.gov/ct2/show/NCT01486524. Accessed Oct 3, 2012.
36.	Guyatt G, Oxman A, Montori V, et al. GRADE指南: Ⅴ.證據質量評價—發表偏倚. 中國循證醫學雜志, 2011, 11(12): 1430-1434.

1. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med, 2003, 348(12): 1546-1554.
2. Hall MJ, Williams SN, DeFrances CJ, et al. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief, 2011, (62): 1-8.
3. Brun-Buisson C. Epidemiology of severe sepsis. Presse Médicale, 2006, 35(3 Pt 2): 513-520.
4. Danai PA, Sinha S, Moss M, et al. Seasonal variation in the epidemiology of sepsis. Critical Care Medicine, 2007, 35(2): 410-415.
5. Das UN. Critical advances in septicemia and septic shock. Criti Care, 2000, 4(5): 290-296.
6. Khwannimit B, Bhurayanontachai R. The epidemiology of, and risk factors for, mortality from severe sepsis and septic shock in a tertiary-care university hospital setting. Epidemiology and Infection, 2009, 137(9): 1-9.
7. Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care, 2004, 8(4): 222-226.?.
8. Brun-Buisson C, Meshaka P, Pinton P, et al. EPISEPSIS: a reappraisal of the epidemiology and out- come of severe sepsis in French intensive care units. Intensive Care Med, 2004, 30(4): 580-588.
9. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001, 29(7): 1303-1313.
10. Cheng B, Xie G, Yao S, et al. Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Critical Care Medicine, 2007, 35(11): 2538-2546.
11. Paul M. Is there a treatment for sepsis other than antibiotics? Clinical Microbiology and Infection, 2009, 15(4): 297.
12. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med, 2003, 348(2): 138-150.
13. Grey ST, Hancock WW. Inhibition of LPS-induced activation of human monocytes by activated protein C (APC) occurs through a novel mechanism. J Leukoc Biol, 1993, 114(6): A487.
14. Bernard GR, Vincent JL, Laterre PF, et al, and the Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. E?cacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med, 2001, 344(5): 699-709.
15. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011, Available from: www.cochrane-handbook.org.
16. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
17. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ, 2003, 327()7414: 557-560.
18. Egger M, Altman DG, Smith GD. Systematic reviews in health-care: meta-analysis in context. 2nd Ed. BMJ Books, Wiley: London, 2001.
19. . Bernard GR, Ely EW, Wright TJ, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med, 2001, 29(11): 2051-2059.
20. Angus DC, Laterre PF, Helterbrand J, et al, and PROWESS Investigators. The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis. Crit Care Med, 2004, 32(11): 2199-2206.
21. Abraham E, Laterre PF, Garg R, et al, and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med, 2005, 353(13): 1332-1341.
22. Dhainaut JF, Antonelli M, Wright P, et al. Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock. Intensive Care Med, 2009, 35(7): 1187-1195.
23. Ranieri VM, Thompson BT, Barie PS, et al, and PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med, 2012, 366(22): 2055-2064.
24. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet, 2005, 365(9453): 63-78.
25. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood, 2007, 109(8): 3161-3172.
26. Shorr AF, Bernard GR, Dhainaut JF, et al. Protein C concentrations in severe sepsis: An early directional change in plasma levels predicts outcome. Crit Care, 2006, 10(6): R92.
27. MammenE. Thehaematological manifestations of sepsis. J Antimicrob Chemother, 1998, 41(Suppl A): S17-S24.
28. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med, 2008, 36(12): 296-327.
29. Casserly B, Gerlach H, Phillips GS, et al. Evaluating the use of recombinant human activated protein C in adult severe sepsis: results of the Surviving Sepsis Campaign. Crit Care Med, 2012, 40(5): 1417-1426.
30. Kalil AC, Larosa SP. Effectiveness and safety of drotrecogin alfa (activated) for severe sepsis: a meta-analysis and metaregression. Lancet Infect Dis, 2012, 12(9): 678-686.
31. Rimmer E, Kumar A, Doucette S, et al, and Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Activated protein C and septic shock: A propensity-matched cohort study. Crit Care Med, 2012, 40(11): 2974-2981.
32. Martí-Carvajal AJ, Solà I, Lathyris D, et al. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev, 2012, 3: CD004388.
33. Nadel S, Goldstein B, Williams MD, et al, and Researching severe Sepsis and Organ dysfunction in children: a global perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet, 2007, 369(9564): 836-843.
34. University of Versailles: Activated protein C and corticosteroids for human septic shock (APROCCHS). Available from: http://clinicaltrials.gov/ct2/show/NCT00625209. Accessed Oct 3, 2012.
35. University of Versailles: Pharmacogenomic Biomarker Study for Recombinant Human Activated Protein C Treatment in Severe Sepsis. Available from: http://clinicaltrials.gov/ct2/show/NCT01486524. Accessed Oct 3, 2012.
36. Guyatt G, Oxman A, Montori V, et al. GRADE指南: Ⅴ.證據質量評價—發表偏倚. 中國循證醫學雜志, 2011, 11(12): 1430-1434.

《中國循證醫學雜志》

人類重組活化蛋白C治療嚴重膿毒癥的Meta分析

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《中國循證醫學雜志》

人類重組活化蛋白C治療嚴重膿毒癥的Meta分析

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