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

Research output: Contribution to journalArticleResearchpeer-review

149 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2223-2234
Number of pages12
JournalNew England Journal of Medicine
Volume376
Issue number23
DOIs
Publication statusPublished - 8 Jun 2017

Cite this

@article{64740cf2e695420ab180dbccb537698d,
title = "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, 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.",
author = "Rowan, {Kathryn M.} and Michael Bailey and Rinaldo Bellomo and Anthony Delaney and Higgins, {Alisa M.} and Belinda Howe and Peake, {Sandra L.} and Reade, {Michael C.}",
year = "2017",
month = "6",
day = "8",
doi = "10.1056/NEJMoa1701380",
language = "English",
volume = "376",
pages = "2223--2234",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "23",

}

Early, goal-directed therapy for septic shock - A patient-level meta-analysis. / Rowan, Kathryn M.; Bailey, Michael; Bellomo, Rinaldo; Delaney, Anthony; Higgins, Alisa M.; Howe, Belinda; Peake, Sandra L.; Reade, Michael C.

In: New England Journal of Medicine, Vol. 376, No. 23, 08.06.2017, p. 2223-2234.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Early, goal-directed therapy for septic shock - A patient-level meta-analysis

AU - Rowan, Kathryn M.

AU - Bailey, Michael

AU - Bellomo, Rinaldo

AU - Delaney, Anthony

AU - Higgins, Alisa M.

AU - Howe, Belinda

AU - Peake, Sandra L.

AU - Reade, Michael C.

PY - 2017/6/8

Y1 - 2017/6/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020281572&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1701380

DO - 10.1056/NEJMoa1701380

M3 - Article

VL - 376

SP - 2223

EP - 2234

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -