Intensive Care Medicine

, Volume 41, Issue 9, pp 1549–1560

A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators

  • D. C. Angus
  • A. E. Barnato
  • D. Bell
  • R. Bellomo
  • C.-R. Chong
  • T. J. Coats
  • A. Davies
  • A. Delaney
  • D. A. Harrison
  • A. Holdgate
  • B. Howe
  • D. T. Huang
  • T. Iwashyna
  • J. A. Kellum
  • S. L. Peake
  • F. Pike
  • M. C. Reade
  • K. M. Rowan
  • M. Singer
  • S. A. R. Webb
  • L. A. Weissfeld
  • D. M. Yealy
  • J. D. Young
Seven-Day Profile Publication

DOI: 10.1007/s00134-015-3822-1

Cite this article as:
Angus, D.C., Barnato, A.E., Bell, D. et al. Intensive Care Med (2015) 41: 1549. doi:10.1007/s00134-015-3822-1

Abstract

Purpose

To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock.

Methods

Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay.

Results

From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % [495/2134] versus control: 22.4 % [582/2601]; pooled OR 1.01 [95 % CI 0.88–1.16], P = 0.9, with heterogeneity [I2 = 57 %; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95 % CI 0.86–1.15), P = 0.93] with no heterogeneity (I2 = 0.0 %; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95 % CI 1.10–1.41]; P < 0.001) and ICU admission [OR 2.19 (95 % CI 1.82–2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I2 = 71 %; P < 0.001) but did not change overall results [pooled OR 0.94 (95 % CI 0.82 to 1.07); P = 0.33].

Conclusion

EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Keywords

Early goal-directed therapy or EGDT Resuscitation Septic shock Central venous oxygen saturation Meta-analysis Systematic review Randomised clinical trials 

Supplementary material

134_2015_3822_MOESM1_ESM.docx (114 kb)
Supplementary material 1 (DOCX 113 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • D. C. Angus
    • 1
  • A. E. Barnato
    • 3
  • D. Bell
    • 4
    • 5
  • R. Bellomo
    • 6
    • 7
  • C.-R. Chong
    • 8
    • 9
  • T. J. Coats
    • 10
  • A. Davies
    • 6
    • 11
  • A. Delaney
    • 6
    • 12
    • 26
  • D. A. Harrison
    • 13
    • 14
  • A. Holdgate
    • 15
  • B. Howe
    • 6
  • D. T. Huang
    • 1
  • T. Iwashyna
    • 6
    • 16
  • J. A. Kellum
    • 1
  • S. L. Peake
    • 6
    • 9
    • 25
  • F. Pike
    • 1
  • M. C. Reade
    • 17
    • 18
  • K. M. Rowan
    • 13
    • 14
    • 19
    • 20
  • M. Singer
    • 21
  • S. A. R. Webb
    • 6
    • 22
  • L. A. Weissfeld
    • 23
  • D. M. Yealy
    • 2
  • J. D. Young
    • 24
  1. 1.Department of Critical Care MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of Emergency MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Faculty of MedicineImperial College LondonLondonUK
  5. 5.Department of Acute MedicineChelsea and Westminster Hospital NHS Foundation TrustLondonUK
  6. 6.Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
  7. 7.Austin HospitalMelbourneAustralia
  8. 8.Pharmacy DepartmentThe Queen Elizabeth HospitalAdelaideAustralia
  9. 9.School of MedicineUniversity of AdelaideAdelaideAustralia
  10. 10.Department of Cardiovascular SciencesUniversity of LeicesterLeicesterUK
  11. 11.Frankston HospitalFrankstonAustralia
  12. 12.Royal North Shore Hospital and University of SydneySydneyAustralia
  13. 13.Clinical Trials UnitIntensive Care National Audit and Research CentreLondonUk
  14. 14.London School of Hygiene and Tropical MedicineLondonUK
  15. 15.Liverpool Hospital and University of NSWSydneyAustralia
  16. 16.University of Michigan and VA Centre for Clinical Management ResearchAnn ArborUSA
  17. 17.Burns, trauma and critical care research centreUniversity of QueenslandBrisbaneAustralia
  18. 18.Joint Health CommandAustralian Defence ForceCanberraAustralia
  19. 19.Department of Health Services Research and PolicyLondon School of Hygiene and Tropical MedicineLondonUK
  20. 20.Division of Research StrategyUniversity College LondonLondonUK
  21. 21.Bloomsbury Institute of Intensive Care MedicineUniversity College LondonLondonUK
  22. 22.Royal Perth Hospital and University of Western AustraliaPerthAustralia
  23. 23.Statistics CollaborativeWashingtonUSA
  24. 24.Nuffield Division of AnaestheticsUniversity of OxfordOxfordUK
  25. 25.Department of Intensive Care MedicineThe Queen Elizabeth HospitalWoodvilleAustralia
  26. 26.Northern Clinical School, Sydney Medical SchoolUniversity of SydneySydneyAustralia