TY - JOUR
T1 - Trial of early, goal-directed resuscitation for septic shock
AU - For The ProMISe Trial Investigators
AU - Mouncey, Paul R.
AU - Osborn, Tiffany M.
AU - Power, G. Sarah
AU - Harrison, David A.
AU - Sadique, M. Zia
AU - Grieve, Richard D.
AU - Jahan, Rahi
AU - Harvey, Sheila E.
AU - Bell, Derek
AU - Bion, Julian F.
AU - Coats, Timothy J.
AU - Singer, Mervyn
AU - Young, J. Duncan
AU - Rowan, Kathryn M.
N1 - Publisher Copyright:
Copyright © 2015 Massachusetts Medical Society. All rights reserved.
PY - 2015/4/2
Y1 - 2015/4/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84926301084&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1500896
DO - 10.1056/NEJMoa1500896
M3 - Article
C2 - 25776532
AN - SCOPUS:84926301084
SN - 0028-4793
VL - 372
SP - 1301
EP - 1311
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 14
ER -