title: Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  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.
authors.forename: Changsong
authors.initials: C
authors.lastname: Wang
authors.forename: Chunjie
authors.initials: C
authors.lastname: Chi
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Libo
authors.initials: L
authors.lastname: Guo
authors.forename: Jiaxiao
authors.initials: J
authors.lastname: Sun
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Xuenan
authors.initials: X
authors.lastname: Chang
authors.forename: Enyou
authors.initials: E
authors.lastname: Li
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000925:Anticoagulants; D006493:Heparin