title: Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis.
abstract: BACKGROUND
  Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.
  
  
  METHODS
  We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.
  
  
  RESULTS
  A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72-0.94; P = 0.008;   I (2) =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67-0.91; P = 0.002; I (2) = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33-1.06; P = 0.28; I(2) = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, -0.04-1.02; P = 0.07; I (2) = 0%).
  
  
  CONCLUSIONS
  The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, International campus (TUMS-IC), Tehran, Iran ; Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Faculty of Medicine, Tehran, Iran ; Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran ; Department of clinical Pharmacy, Colleague of Public health and Medical Sciences, Jimma University, Jimma, Ethiopia.
authors.forename: Legese
authors.initials: L
authors.lastname: Chelkeba
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Faculty of Medicine, Tehran, Iran.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Faculty of Medicine, Tehran, Iran.
authors.forename: Atabak
authors.initials: A
authors.lastname: Najafi
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, International campus (TUMS-IC), Tehran, Iran ; Department of Anesthesiology and Critical Care Medicine, Sina Hospital, Faculty of Medicine, Tehran, Iran ; Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Mojtahedzadeh
keywords: Duration of mechanical ventilation; duration of vasopressor therapy; early goal-directed therapy; length of Intensive Care Unit stay; length of hospital stay; overall mortality; sepsis; septic shock; severe sepsis