title: Early Goal-Directed Therapy in Severe Sepsis and Septic Shock: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  The Surviving Sepsis Campaign guidelines recommend early goal-directed therapy (EGDT) for the resuscitation of patients with sepsis; however, the recent evidences quickly evolve and convey conflicting results. We performed a meta-analysis to evaluate the effect of EGDT on mortality in adults with severe sepsis and septic shock.
  
  
  METHODS
  We searched electronic databases to identify randomized controlled trials that compared EGDT with usual care or lactate-guided therapy in adults with severe sepsis and septic shock. Predefined primary outcome was all-cause mortality at final follow-up.
  
  
  RESULTS
  We included 13 trials enrolling 5268 patients. Compared with usual care, EGDT was associated with decreased mortality (risk ratio [RR]: 0.87, 95% CI: 0.77-0.98; 4664 patients, 8 trials; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] quality of evidence was moderate). Compared with lactate clearance-guided therapy, EGDT was associated with increased mortality (RR: 1.60, 95% CI: 1.24-2.06; 604 patients, 5 trials; GRADE quality of evidence was low). Patients assigned to EGDT received more intravenous fluid, red cell transfusion, vasopressor infusion, and dobutamine use within the first 6 hours than those assigned to usual care (all P values < .00001).
  
  
  CONCLUSIONS
  Adults with severe sepsis and septic shock who received EGDT had a lower mortality than those given usual care, the benefit may mainly be attributed to treatments administered within the first 6 hours. However, the underlying mechanisms by which lactate clearance-guided therapy benefits these patients are yet to be investigated.
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Teng
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xia
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Sun
authors.affiliation: 1 Department of Blood Transfusion, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ai-Qing
authors.initials: AQ
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D000074388:Early Goal-Directed Therapy / Q000706:statistics & numerical data*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012151:Resuscitation / Q000379:methods / Q000401:mortality*; D018805:Sepsis / Q000401:mortality* / Q000628:therapy*; D012772:Shock, Septic / Q000401:mortality* / Q000628:therapy*; D013997:Time Factors; D061665:Time-to-Treatment / Q000706:statistics & numerical data; D016896:Treatment Outcome
keywords: early goal-directed therapy; lactate clearance; meta-analysis; mortality; septic shock; severe sepsis