Trial of early, goal-directed resuscitation for septic shock

Research output: Contribution to journalArticle

Authors

  • Paul R Mouncey
  • Tiffany M Osborn
  • G Sarah Power
  • David A Harrison
  • M Zia Sadique
  • Richard D Grieve
  • Rahi Jahan
  • Sheila E Harvey
  • Derek Bell
  • Julian Bion
  • Timothy J Coats
  • Mervyn Singer
  • J Duncan Young
  • Kathryn M Rowan
  • ProMISe Trial Investigators

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.).

Details

Original languageEnglish
Pages (from-to)1301-11
Number of pages11
JournalThe New England Journal of Medicine
Volume372
Issue number14
Publication statusPublished - 2 Apr 2015

Keywords

  • Adult, Aged, Anti-Bacterial Agents, Blood Transfusion, Clinical Protocols, Combined Modality Therapy, Cost-Benefit Analysis, Female, Fluid Therapy, Humans, Infusions, Intravenous, Kaplan-Meier Estimate, Male, Middle Aged, Practice Guidelines as Topic, Quality of Life, Quality-Adjusted Life Years, Resuscitation, Shock, Septic, Vasoconstrictor Agents