Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

PRISM Investigators

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

2020-08-30T16:12:10Z

2020-08-30T16:12:10Z

2017-06

2020-08-30T16:12:10Z

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 .).

0028-4793

1533-4406

https://hdl.handle.net/10161/21358

eng

Massachusetts Medical Society

The New England journal of medicine

10.1056/nejmoa1701380

PRISM Investigators

Humans

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

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

Journal article

2223

2234

23

School of Medicine

Surgery, Emergency Medicine

Duke

Surgery

Clinical Science Departments

Published

376