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Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.
journal contributionposted on 2017-07-31, 10:44 authored by PRISM Investigators, Kathryn M. Rowan, Derek C. Angus, Michael Bailey, Amber E. Barnato, Rinaldo Bellomo, Ruth R. Canter, Timothy J. Coats, Anthony Delaney, Elizabeth Gimbel, Richard D. Grieve, David A. Harrison, Alisa M. Higgins, Belinda Howe, David T. Huang, John A. Kellum, Paul R. Mouncey, Edvin Music, Sandra L. Peake, Francis Pike, Michael C. Reade, M. Zia Sadique, Mervyn Singer, Donald M. Yealy
BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed 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 protocol-based 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 treatment-by-subgroup 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. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).
Supported in part by grants from the U.S. National Institute of General Medical Sciences, National Institutes of Health (P50 GM076659) (ProCESS trial); the National Health and Medical Research Council of Australia (491075 and 1021165), the Intensive Care Foundation, and the Alfred Foundation (ARISE trial); and the United Kingdom National Institute for Health Research Health Technology Assessment Programme (07/37/47) (ProMISe trial)
CitationNew England Journal of Medicine, 376 (23), pp. 2223-2234
Author affiliation/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences
- VoR (Version of Record)
Published inNew England Journal of Medicine
PublisherMassachusetts Medical Society
NotesThe file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
AgedCardiotonic AgentsCombined Modality TherapyCost-Benefit AnalysisErythrocyte TransfusionFemaleFluid TherapyHospital MortalityHospitalizationHumansInfusions, IntravenousMaleMiddle AgedPractice Guidelines as TopicQuality-Adjusted Life YearsRandomized Controlled Trials as TopicResuscitationShock, SepticSurvival AnalysisTreatment OutcomeVasoconstrictor Agents