Early, goal-directed therapy for septic shock - a patient-level meta-analysis

Rowan, Kathryn M., Angus, Derek C., Bailey, Michael, Barnato, Amber E., Bellomo, Rinaldo, Canter, Ruth R., Coats, Timothy J., Delaney, Anthony, Gimbel, Elizabeth, Grieve, Richard D., Harrison, David A., Higgins, Alisa M., Howe, Belinda, Huang, David T., Kellum, John A., Mouncey, Paul R., Music, Edvin, Peake, Sandra L., Pike, Francis, Reade, Michael C., Sadique, M. Zia, Singer, Mervyn and Yealy, Donald M. (2017) Early, goal-directed therapy for septic shock - a patient-level meta-analysis. New England Journal of Medicine, 376 23: 2223-2234. doi:10.1056/NEJMoa1701380

Author Rowan, Kathryn M.
Angus, Derek C.
Bailey, Michael
Barnato, Amber E.
Bellomo, Rinaldo
Canter, Ruth R.
Coats, Timothy J.
Delaney, Anthony
Gimbel, Elizabeth
Grieve, Richard D.
Harrison, David A.
Higgins, Alisa M.
Howe, Belinda
Huang, David T.
Kellum, John A.
Mouncey, Paul R.
Music, Edvin
Peake, Sandra L.
Pike, Francis
Reade, Michael C.
Sadique, M. Zia
Singer, Mervyn
Yealy, Donald M.
Title Early, goal-directed therapy for septic shock - a patient-level meta-analysis
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 1533-4406
Publication date 2017-06-08
Year available 2017
Sub-type Article (original research)
DOI 10.1056/NEJMoa1701380
Open Access Status Not yet assessed
Volume 376
Issue 23
Start page 2223
End page 2234
Total pages 12
Place of publication Waltham, MA, United States
Publisher Massachussetts Medical Society
Language eng
Subject 2700 Medicine
Formatted abstract
Background: After a single-center trial and observational studies suggesting that early, goaldirected therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.

Methods: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocolbased standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatmentbysubgroup interactions for 16 patient characteristics and 6 care-delivery characteristics.

Results: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P = 0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P = 0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P = 0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.

Conclusions: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics.
Keyword Severe Sepsis
Personalized Medicine
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID P50 GM076659
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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