title: Trial of early, goal-directed resuscitation for septic shock.
abstract: BACKGROUND
  Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains.
  
  
  METHODS
  We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days.
  
  
  RESULTS
  We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.
  
  
  CONCLUSIONS
  In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).
authors.affiliation: From the Clinical Trials Unit, Intensive Care National Audit and Research Centre (P.R.M., G.S.P., D.A.H., R.J., S.E.H., K.M.R.), Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine (M.Z.S., R.D.G.), and Faculty of Medicine, Imperial College London (D.B.), Department of Acute Medicine, Chelsea and Westminster Hospital NHS Foundation Trust (D.B.), and Bloomsbury Institute of Intensive Care Medicine, University College London (M.S.), London, the Department of Intensive Care Medicine, University of Birmingham, Birmingham (J.F.B.), Department of Cardiovascular Sciences, University of Leicester, Leicester (T.J.C.), and Nuffield Division of Anaesthetics, University of Oxford, Oxford (J.D.Y.) - all in the United Kingdom; and the Departments of Surgery and Emergency Medicine, Washington University at St. Louis, St. Louis (T.M.O.).
authors.forename: Paul R
authors.initials: PR
authors.lastname: Mouncey
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Osborn
authors.forename: G Sarah
authors.initials: GS
authors.lastname: Power
authors.forename: David A
authors.initials: DA
authors.lastname: Harrison
authors.forename: M Zia
authors.initials: MZ
authors.lastname: Sadique
authors.forename: Richard D
authors.initials: RD
authors.lastname: Grieve
authors.forename: Rahi
authors.initials: R
authors.lastname: Jahan
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Harvey
authors.forename: Derek
authors.initials: D
authors.lastname: Bell
authors.forename: Julian F
authors.initials: JF
authors.lastname: Bion
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Coats
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: J Duncan
authors.initials: JD
authors.lastname: Young
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rowan
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001803:Blood Transfusion; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D005260:Female; D005440:Fluid Therapy; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012151:Resuscitation / Q000191:economics / Q000379:methods*; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014662:Vasoconstrictor Agents