This is not the most recent version of the article. View current version (14 MAR 2012)
Intervention Review
Human recombinant activated protein C for severe sepsis
Editorial Group: Cochrane Anaesthesia Group
Published Online: 13 APR 2011
Assessed as up-to-date: 13 MAR 2011
DOI: 10.1002/14651858.CD004388.pub4
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Martí-Carvajal AJ, Solà I, Lathyris D, Cardona AF. Human recombinant activated protein C for severe sepsis. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD004388. DOI: 10.1002/14651858.CD004388.pub4.
Publication History
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 13 APR 2011
This is not the most recent version of the article.View current version (14 Mar 2012)
Abstract
Background
Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been used to reduce the high rate of death by severe sepsis or septic shock. This is an update of a Cochrane review (originally published in 2007 and updated in 2008).
Objectives
We assessed the clinical effectiveness and safety of APC for the treatment of patients with severe sepsis or septic shock.
Search methods
For this updated review we searched CENTRAL (The Cochrane Library 2010, Issue 6); MEDLINE (1966 to June 2010); EMBASE (1980 to July 1, 2010); BIOSIS (1965 to July 1, 2010); CINAHL (1982 to 16 June 2010) and LILACS (1982 to 16 June 2010). There was no language restriction.
Selection criteria
We included randomized controlled trials (RCTs) assessing the effects of APC for severe sepsis in adults and children. We excluded studies on neonates. We considered all-cause mortality at day 28, at the end of study follow up, and hospital mortality as the primary outcomes.
Data collection and analysis
We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I
Main results
We identified one new RCT in this update. We included a total of five RCTs involving 5101 participants. For 28-day mortality, APC did not reduce the risk of death in adult participants with severe sepsis (pooled RR 0.97, 95% confidence interval (CI) 0.78 to 1.22; P = 0.82, I
Authors' conclusions
This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. Additionally, APC is associated with a higher risk of bleeding. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC.
Plain language summary
Human recombinant activated protein C for severe sepsis
Current evidence does not support the use of human recombinant activated protein C in adults or children with severe sepsis or septic shock; moreover, there is an increased risk of bleeding associated with its use.
Sepsis is a major cause of death in the intensive care unit. It is a complex syndrome resulting from a presumed or known infection and its pathogenesis involves interactions between inflammation and blood clotting pathways. This serious medical condition is characterized by an inflammatory response to an infection which can affect the whole body. Patients with sepsis may have developed the inflammatory response because of microbes in their blood, urine, lungs, skin or other tissues. Severe sepsis can lead to multiple organ failure due to blood clotting in the finer blood vessels. This reduces the amount of blood reaching the organs. Protein C reduces the clotting process and a lack of protein C can lead to an exaggeration of blood clotting phenomena. Sepsis decreases protein C levels in the body. It has been suggested that treatment with human recombinant activated protein C (APC) will increase the levels and prevent multiple organ failure. In this updated review we included five randomized controlled trials which included 5101 participants with either a high or low risk of death. We found no evidence suggesting that APC reduced the risk of death in adults or children with severe sepsis. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC in patients with severe sepsis.
摘要
背景
人類重組活化蛋白C與敗血症
敗血症是一個常見，致命的狀況，而且也花費醫療成本。因此，尋求新的治療對策以降低其死亡率是刻不容緩的一件事。其中一個方式便是人類重組活化蛋白C的使用。
目標
我們評估了使用人類重組活化蛋白C來治療嚴重敗血症及敗血性休克的成效。
搜尋策略
我們由the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 2);MEDLINE (1966to 2005); EMBASE (1980 to 2005) and LILACS (1982 to 2005)等資料庫搜尋資料。此外，我們向各研究者與機構請教，並沒有限制在任何一個語言的研究。
選擇標準
我們蒐集了隨機對照試驗，評估了使用人類重組活化蛋白C來治療成人及孩童嚴重敗血症的成效，但我們排除了對於新生兒的研究。
資料收集與分析
我們分別且獨立的完成試驗的選取，品質的評估，以及資料的擷取。我們評估以二分法結果的相對危險(relative risk, RR)。我們使用Isquared計算了數據的異質性。我們使用了隨機效應模型。
主要結論
我們所納入的研究一共包括4911位參與者(4434位成人及477位孩童病患)。以28天內死亡率來說，人類重組活化蛋白C並不能降低嚴重敗血症成人病患之死亡危險(pooled RR 0.92, 95% confidence interval (CI) 0.72 to 1.18; P = 0.50, I2 = 72%)。使用人類重組活化蛋白C的有效與否也與敗血症的嚴重程度沒有相關。有兩個研究可以證實：其中一個研究APACHE II score小於25者，參與者的相對危險是1.04 (95% CI 0.89 to 1.21; P = 0.70)；另一個研究APACHE II score大於25者，參與者的相對危險是0.90 (95% CI 0.54 to 1.49; P = 0.68)。相反的，使用人類重組活化蛋白C反而使病患發生出血的危險性增加(RR 1.48；95% CI 1.07 to 2.06; P = 0.02, I2 = 8%)。我們所納入的研究中有兩個便因為無法達到有效的治療功效而停止試驗。
作者結論
本篇更新的綜論文章並沒有發現足夠的證據支持應將人類重組活化蛋白C用於嚴重敗血症及敗血性休克的治療。此外，使用人類重組活化蛋白C反而增加病患出血的危險性。除非有其他一些新的隨機對照試驗結果可以提供足夠證據說明人類重組活化蛋白C的療效，否則臨床醫師，決策者，或是學界都不應鼓吹人類重組活化蛋白C的使用。
翻譯人
本摘要由慈濟醫院黃佳君翻譯。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
總結
目前為止並沒有足夠的證據支持應將人類重組活化蛋白C用於治療成人及孩童的嚴重敗血症，此外，它還有可能增加內出血的危險。敗血症是加護病房內的主要死因之一，它是由一些假定的或已知的感染所引起的複雜症候群，而且極難治療，嚴重者可能引發多重器官衰竭。敗血症可能導致蛋白C的量下降，因此原先學者認為給予病患人類重組活化蛋白C應可增加蛋白C的量而避免多重器官衰竭。本篇更新的綜論文章並沒有發現足夠的證據支持人類重組活化蛋白C可以減低成人或孩童嚴重敗血症的死亡率及危險。