Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.
Abstract
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 .).
Type
Journal articleSubject
PRISM InvestigatorsHumans
Shock, Septic
Cardiotonic Agents
Vasoconstrictor Agents
Treatment Outcome
Erythrocyte Transfusion
Combined Modality Therapy
Fluid Therapy
Resuscitation
Hospitalization
Infusions, Intravenous
Hospital Mortality
Survival Analysis
Quality-Adjusted Life Years
Aged
Middle Aged
Cost-Benefit Analysis
Female
Male
Randomized Controlled Trials as Topic
Practice Guidelines as Topic
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https://hdl.handle.net/10161/21358Published Version (Please cite this version)
10.1056/nejmoa1701380Publication Info
PRISM Investigators; Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber
E; Bellomo, Rinaldo; ... Yealy, Donald M (2017). Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis. The New England journal of medicine, 376(23). pp. 2223-2234. 10.1056/nejmoa1701380. Retrieved from https://hdl.handle.net/10161/21358.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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