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Published in: Critical Care 5/2014

Open Access 01-10-2014 | Research

Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis

Authors: Changsong Wang, Chunjie Chi, Lei Guo, Xiaoyang Wang, Libo Guo, Jiaxiao Sun, Bo Sun, Shanshan Liu, Xuenan Chang, Enyou Li

Published in: Critical Care | Issue 5/2014

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Abstract

Introduction

There are approximately 19 million new cases of sepsis worldwide each year. Among them, more than one quarter of patients die. We aimed to assess the effects of heparin on short-term mortality in adult patients with sepsis and severe sepsis.

Methods

We searched electronic databases (Medline, Embase, and Cochrane Library databases; the Cochrane Controlled Trials Register) and conference proceedings (Web of Knowledge (Conference Proceedings Citation Index - Science, Conference Proceedings Citation Index - Social Sciences & Humanities)) from inception to July 2014, expert contacts and relevant websites. Controlled trials of heparin versus placebo in sepsis or severe sepsis were identified. In total two reviewers independently assessed eligibility, and four authors independently extracted data; consensus was reached by conference. We used the chi-square test and I2 to assess statistical heterogeneity (P <0.05). The primary analysis was based on the fixed-effect model to produce pooled odds ratios with 95% confidence intervals.

Results

A total of nine publications were included in the meta-analysis. Heparin decreased 28-day mortality (n = 3,482, OR = 0.656, 95% CI = 0.562 to 0.765, P <0.0001). According to the meta-analysis of 28-day mortality, heterogeneity was not found among the eight randomized clinical trials (RCTs) (I2 = 0.0%). Heparin had no effect on bleeding events in sepsis (seven RCTs, n = 2,726; OR = 1.063; 95% CI = 0.834 to 1.355; P = 0.623; and I2 = 20.9%). Subgroup analysis demonstrated that the sample size may be a source of heterogeneity, but experimental design was not.

Conclusions

Heparin may reduce 28-day mortality in patients with severe sepsis, at the same time, there was no increase in the risk of bleeding in the heparin group. We recommend the use of heparin for sepsis and severe sepsis.
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Literature
1.
go back to reference Angus DC, van der Poll T: Severe sepsis and septic shock. N Engl J Med. 2013, 369: 840-851. 10.1056/NEJMra1208623.CrossRef Angus DC, van der Poll T: Severe sepsis and septic shock. N Engl J Med. 2013, 369: 840-851. 10.1056/NEJMra1208623.CrossRef
2.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83af.CrossRef Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83af.CrossRef
3.
go back to reference Martinez JT, Fernandez G, Vazquez-Leon H: Clinical evaluation of new therapeutic concepts in septic shock. Obstet Gynecol. 1966, 27: 296-301. Martinez JT, Fernandez G, Vazquez-Leon H: Clinical evaluation of new therapeutic concepts in septic shock. Obstet Gynecol. 1966, 27: 296-301.
4.
go back to reference Zhao C, Zhang ZD, Zhang XJ, Li X, Zhu R, Ma XC: Evaluation of clinical effects on low-dose heparin therapy for sepsis. Zhonghua Nei Ke Za Zhi. 2009, 48: 566-569. Zhao C, Zhang ZD, Zhang XJ, Li X, Zhu R, Ma XC: Evaluation of clinical effects on low-dose heparin therapy for sepsis. Zhonghua Nei Ke Za Zhi. 2009, 48: 566-569.
5.
go back to reference Levi M, Levy M, Williams MD, Douglas I, Artigas A, Antonelli M, Wyncoll D, Janes J, Booth FV, Wang D, Sundin DP, Macias WL: Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med. 2007, 176: 483-490. 10.1164/rccm.200612-1803OC.CrossRef Levi M, Levy M, Williams MD, Douglas I, Artigas A, Antonelli M, Wyncoll D, Janes J, Booth FV, Wang D, Sundin DP, Macias WL: Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med. 2007, 176: 483-490. 10.1164/rccm.200612-1803OC.CrossRef
6.
go back to reference Jaimes F, de la Rosa G: Anticoagulation and sepsis: the opportunity for a new use of heparin?. Biomedica. 2006, 26: 150-160. 10.7705/biomedica.v26i1.1404.CrossRef Jaimes F, de la Rosa G: Anticoagulation and sepsis: the opportunity for a new use of heparin?. Biomedica. 2006, 26: 150-160. 10.7705/biomedica.v26i1.1404.CrossRef
7.
go back to reference Zhang XJ, Ma XC: Therapeutic effects of early administration of low-dose heparin in patients with severe sepsis. Zhonghua Wai Ke Za Zhi. 2006, 44: 1209-1211. Zhang XJ, Ma XC: Therapeutic effects of early administration of low-dose heparin in patients with severe sepsis. Zhonghua Wai Ke Za Zhi. 2006, 44: 1209-1211.
8.
go back to reference Ai YH, Zhang LN, Gong H, Xu DM, Zhao SP, Chen JH: Clinical study of low molecular weight heparin therapy for sepsis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005, 17: 736-739. Ai YH, Zhang LN, Gong H, Xu DM, Zhao SP, Chen JH: Clinical study of low molecular weight heparin therapy for sepsis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005, 17: 736-739.
9.
go back to reference Iba T, Saito D, Wada H, Asakura H: Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012, 130: e129-e133. 10.1016/j.thromres.2012.03.021.CrossRef Iba T, Saito D, Wada H, Asakura H: Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012, 130: e129-e133. 10.1016/j.thromres.2012.03.021.CrossRef
10.
go back to reference Kirschenbaum LA, Lopez WC, Ohrum P, Tsen A, Khazin J, Astiz ME: Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock. Crit Care Med. 2006, 34: 2207-2212. 10.1097/01.CCM.0000229880.41513.86.CrossRef Kirschenbaum LA, Lopez WC, Ohrum P, Tsen A, Khazin J, Astiz ME: Effect of recombinant activated protein C and low-dose heparin on neutrophil-endothelial cell interactions in septic shock. Crit Care Med. 2006, 34: 2207-2212. 10.1097/01.CCM.0000229880.41513.86.CrossRef
11.
go back to reference Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996, 17: 1-12. 10.1016/0197-2456(95)00134-4.CrossRef Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996, 17: 1-12. 10.1016/0197-2456(95)00134-4.CrossRef
12.
go back to reference Silber S: A new and rapid scoring system to assess the scientific evidence from clinical trials. J Interv Cardiol. 2006, 19: 485-492. 10.1111/j.1540-8183.2006.00205.x.CrossRef Silber S: A new and rapid scoring system to assess the scientific evidence from clinical trials. J Interv Cardiol. 2006, 19: 485-492. 10.1111/j.1540-8183.2006.00205.x.CrossRef
13.
go back to reference Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008, 336: 1006-1009. 10.1136/bmj.39537.939039.BE.CrossRef Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A: Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008, 336: 1006-1009. 10.1136/bmj.39537.939039.BE.CrossRef
14.
go back to reference Spruance SL, Reid JE, Grace M, Samore M: Hazard ratio in clinical trials. Antimicrob Agents Chemother. 2004, 48: 2787-2792. 10.1128/AAC.48.8.2787-2792.2004.CrossRef Spruance SL, Reid JE, Grace M, Samore M: Hazard ratio in clinical trials. Antimicrob Agents Chemother. 2004, 48: 2787-2792. 10.1128/AAC.48.8.2787-2792.2004.CrossRef
15.
go back to reference Moran J, Solomon P, Warn D: Methodology in meta-analysis: a study from critical care meta-analytic practice. Health Serv Outcomes Res Methodol. 2004, 5: 207-226. 10.1007/s10742-006-6829-9.CrossRef Moran J, Solomon P, Warn D: Methodology in meta-analysis: a study from critical care meta-analytic practice. Health Serv Outcomes Res Methodol. 2004, 5: 207-226. 10.1007/s10742-006-6829-9.CrossRef
16.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ. 2003, 327: 557-560. 10.1136/bmj.327.7414.557.CrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ. 2003, 327: 557-560. 10.1136/bmj.327.7414.557.CrossRef
17.
go back to reference Borenstein M, Hedges LV, Higgins JPT: Fixed-effect versus random-effect models. Introduction to Meta-Analysis. 2009, John Wiley & Sons Limited, Chichester, UK, 77-85. 10.1002/9780470743386.ch13.CrossRef Borenstein M, Hedges LV, Higgins JPT: Fixed-effect versus random-effect models. Introduction to Meta-Analysis. 2009, John Wiley & Sons Limited, Chichester, UK, 77-85. 10.1002/9780470743386.ch13.CrossRef
18.
go back to reference Sterne JA, Gavaghan D, Egger M: Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000, 53: 1119-1129. 10.1016/S0895-4356(00)00242-0.CrossRef Sterne JA, Gavaghan D, Egger M: Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000, 53: 1119-1129. 10.1016/S0895-4356(00)00242-0.CrossRef
19.
go back to reference Greenland S: Quality scores are useless and potentially misleading reply to "Re: a critical look at some popular analytic methods". Am J Epidemiol. 1994, 140: 300-301. Greenland S: Quality scores are useless and potentially misleading reply to "Re: a critical look at some popular analytic methods". Am J Epidemiol. 1994, 140: 300-301.
20.
go back to reference Jüni P, Witschi A, Bloch R, Egger M: The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999, 282: 1054-1060. 10.1001/jama.282.11.1054.CrossRef Jüni P, Witschi A, Bloch R, Egger M: The hazards of scoring the quality of clinical trials for meta-analysis. JAMA. 1999, 282: 1054-1060. 10.1001/jama.282.11.1054.CrossRef
21.
go back to reference Detsky AS, Naylor CD, O’Rourke K, McGeer AJ, L’Abbé KA: Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992, 45: 255-265. 10.1016/0895-4356(92)90085-2.CrossRef Detsky AS, Naylor CD, O’Rourke K, McGeer AJ, L’Abbé KA: Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992, 45: 255-265. 10.1016/0895-4356(92)90085-2.CrossRef
22.
go back to reference Emerson JD, Burdick E, Hoaglin DC, Mosteller F, Chalmers TC: An empirical study of thepossible relation of treatment differences to quality scores in controlled randomized clinical trials. Control Clin Trials. 1990, 11: 339-352. 10.1016/0197-2456(90)90175-2.CrossRef Emerson JD, Burdick E, Hoaglin DC, Mosteller F, Chalmers TC: An empirical study of thepossible relation of treatment differences to quality scores in controlled randomized clinical trials. Control Clin Trials. 1990, 11: 339-352. 10.1016/0197-2456(90)90175-2.CrossRef
23.
go back to reference Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Muñoz A: Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study). Crit Care Med. 2009, 37: 1185-1196. 10.1097/CCM.0b013e31819c06bc.CrossRef Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, Muñoz A: Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study). Crit Care Med. 2009, 37: 1185-1196. 10.1097/CCM.0b013e31819c06bc.CrossRef
24.
go back to reference Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Pénzes I, Kübler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001, 286: 1869-1878. 10.1001/jama.286.15.1869.CrossRef Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Pénzes I, Kübler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001, 286: 1869-1878. 10.1001/jama.286.15.1869.CrossRef
25.
go back to reference Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettilä V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA: Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003, 290: 238-247. 10.1001/jama.290.2.238.CrossRef Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettilä V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA: Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003, 290: 238-247. 10.1001/jama.290.2.238.CrossRef
26.
go back to reference Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ: Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001, 344: 699-709. 10.1056/NEJM200103083441001.CrossRef Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ: Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001, 344: 699-709. 10.1056/NEJM200103083441001.CrossRef
27.
go back to reference Yang CH, Guan XD, Chen J, Ouyang B, Chen MY, Li LF, Huang SW, Kou QY, Wu JF: The study of the mechanism of the effect of heparin on tissue perfusion of sepsis patients. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008, 20: 550-552. Yang CH, Guan XD, Chen J, Ouyang B, Chen MY, Li LF, Huang SW, Kou QY, Wu JF: The study of the mechanism of the effect of heparin on tissue perfusion of sepsis patients. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008, 20: 550-552.
28.
go back to reference Liu XL, Wang XZ, Liu XX, Hao D, Jaladat Y, Lu F, Sun T, Lv CJ: Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: a prospective clinical study. Exp Ther Med. 2014, 7: 604-608. Liu XL, Wang XZ, Liu XX, Hao D, Jaladat Y, Lu F, Sun T, Lv CJ: Low-dose heparin as treatment for early disseminated intravascular coagulation during sepsis: a prospective clinical study. Exp Ther Med. 2014, 7: 604-608.
29.
go back to reference Agarwal R, Gupta D: Anticoagulation in sepsis: is low-dose heparin as effective as activated protein C?. Intensive Care Med. 2005, 31: 1297-1298. 10.1007/s00134-005-2723-0.CrossRef Agarwal R, Gupta D: Anticoagulation in sepsis: is low-dose heparin as effective as activated protein C?. Intensive Care Med. 2005, 31: 1297-1298. 10.1007/s00134-005-2723-0.CrossRef
30.
go back to reference Afshari A, Wetterslev J, Brok J, Møller A: Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ. 2007, 335: 1248-1251. 10.1136/bmj.39398.682500.25.CrossRef Afshari A, Wetterslev J, Brok J, Møller A: Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ. 2007, 335: 1248-1251. 10.1136/bmj.39398.682500.25.CrossRef
31.
go back to reference Alhazzani W, Lim W, Jaeschke RZ, Murad MH, Cade J, Cook DJ: Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013, 41: 2088-2098. 10.1097/CCM.0b013e31828cf104.CrossRef Alhazzani W, Lim W, Jaeschke RZ, Murad MH, Cade J, Cook DJ: Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2013, 41: 2088-2098. 10.1097/CCM.0b013e31828cf104.CrossRef
32.
go back to reference Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR: Dynamic evolution of coagulopathy in the first day of severe sepsis: Relationship with mortality and organ failure. Crit Care Med. 2005, 33: 341-348. 10.1097/01.CCM.0000153520.31562.48.CrossRef Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR: Dynamic evolution of coagulopathy in the first day of severe sepsis: Relationship with mortality and organ failure. Crit Care Med. 2005, 33: 341-348. 10.1097/01.CCM.0000153520.31562.48.CrossRef
33.
go back to reference Riewald M, Ruf W: Science review: role of coagulation protease cascades in sepsis. Crit Care. 2003, 7: 123-129. 10.1186/cc1825.CrossRef Riewald M, Ruf W: Science review: role of coagulation protease cascades in sepsis. Crit Care. 2003, 7: 123-129. 10.1186/cc1825.CrossRef
34.
go back to reference Zeerleder S, Hack CE, Wuillemin WA: Disseminated intravascular coagulation in sepsis. Chest. 2005, 128: 2864-2875. 10.1378/chest.128.4.2864.CrossRef Zeerleder S, Hack CE, Wuillemin WA: Disseminated intravascular coagulation in sepsis. Chest. 2005, 128: 2864-2875. 10.1378/chest.128.4.2864.CrossRef
35.
go back to reference Tyrrell DJ, Horne AP, Holme KR, Preuss JM, Page CP: Heparin in inflammation: potential therapeutic applications beyond anticoagulation. Adv Pharmacol. 1999, 46: 151-208. 10.1016/S1054-3589(08)60471-8.CrossRef Tyrrell DJ, Horne AP, Holme KR, Preuss JM, Page CP: Heparin in inflammation: potential therapeutic applications beyond anticoagulation. Adv Pharmacol. 1999, 46: 151-208. 10.1016/S1054-3589(08)60471-8.CrossRef
36.
go back to reference Cornet AD, Smit EG, Beishuizen A, Groeneveld AB: The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost. 2007, 98: 579-586. Cornet AD, Smit EG, Beishuizen A, Groeneveld AB: The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost. 2007, 98: 579-586.
37.
go back to reference Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE: Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011, 364: 1305-1314. 10.1056/NEJMoa1014475.CrossRef Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, Zytaruk N, Crowther M, Geerts W, Cooper DJ, Vallance S, Qushmaq I, Rocha M, Berwanger O, Vlahakis NE: Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011, 364: 1305-1314. 10.1056/NEJMoa1014475.CrossRef
38.
go back to reference Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE: Heparin and low-molecular-weight-heparin mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy and safety. Chest. 2001, 119: 64-94. 10.1378/chest.119.1_suppl.64S.CrossRef Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE: Heparin and low-molecular-weight-heparin mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy and safety. Chest. 2001, 119: 64-94. 10.1378/chest.119.1_suppl.64S.CrossRef
Metadata
Title
Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis
Authors
Changsong Wang
Chunjie Chi
Lei Guo
Xiaoyang Wang
Libo Guo
Jiaxiao Sun
Bo Sun
Shanshan Liu
Xuenan Chang
Enyou Li
Publication date
01-10-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 5/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-014-0563-4

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