title: A randomized trial of protocol-based care for early septic shock.
abstract: BACKGROUND
  In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.
  
  
  METHODS
  In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.
  
  
  RESULTS
  We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.
  
  
  CONCLUSIONS
  In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).
authors.forename: Donald M
authors.initials: DM
authors.lastname: Yealy
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.forename: David T
authors.initials: DT
authors.lastname: Huang
authors.forename: Amber E
authors.initials: AE
authors.lastname: Barnato
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Weissfeld
authors.forename: Francis
authors.initials: F
authors.lastname: Pike
authors.forename: Thomas
authors.initials: T
authors.lastname: Terndrup
authors.forename: Henry E
authors.initials: HE
authors.lastname: Wang
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hou
authors.forename: Frank
authors.initials: F
authors.lastname: LoVecchio
authors.forename: Michael R
authors.initials: MR
authors.lastname: Filbin
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001803:Blood Transfusion; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D004636:Emergency Service, Hospital; D005260:Female; D005440:Fluid Therapy; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012151:Resuscitation / Q000592:standards*; D012772:Shock, Septic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents