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

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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 [I 2 = 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 (I 2 = 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 (I 2 = 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.

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Conflicts of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

    D. C. Angus, D. T. Huang, J. A. Kellum & F. Pike

  2. Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

    D. M. Yealy

  3. Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

    A. E. Barnato

  4. Faculty of Medicine, Imperial College London, London, UK

    D. Bell

  5. Department of Acute Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

    D. Bell

  6. Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    R. Bellomo, A. Davies, A. Delaney, B. Howe, T. Iwashyna, S. L. Peake & S. A. R. Webb

  7. Austin Hospital, Melbourne, VIC, Australia

    R. Bellomo

  8. Pharmacy Department, The Queen Elizabeth Hospital, Adelaide, SA, Australia

    C.-R. Chong

  9. School of Medicine, University of Adelaide, Adelaide, SA, Australia

    C.-R. Chong & S. L. Peake

  10. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

    T. J. Coats

  11. Frankston Hospital, Frankston, VIC, Australia

    A. Davies

  12. Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia

    A. Delaney

  13. Clinical Trials Unit, Intensive Care National Audit and Research Centre, London, Uk

    D. A. Harrison & K. M. Rowan

  14. London School of Hygiene and Tropical Medicine, London, UK

    D. A. Harrison & K. M. Rowan

  15. Liverpool Hospital and University of NSW, Sydney, NSW, Australia

    A. Holdgate

  16. University of Michigan and VA Centre for Clinical Management Research, Ann Arbor, MI, USA

    T. Iwashyna

  17. Burns, trauma and critical care research centre, University of Queensland, Brisbane, QLD, Australia

    M. C. Reade

  18. Joint Health Command, Australian Defence Force, Canberra, ACT, Australia

    M. C. Reade

  19. Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK

    K. M. Rowan

  20. Division of Research Strategy, University College London, London, UK

    K. M. Rowan

  21. Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK

    M. Singer

  22. Royal Perth Hospital and University of Western Australia, Perth, WA, Australia

    S. A. R. Webb

  23. Statistics Collaborative, Washington, DC, USA

    L. A. Weissfeld

  24. Nuffield Division of Anaesthetics, University of Oxford, Oxford, UK

    J. D. Young

  25. Department of Intensive Care Medicine, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA, 5011, Australia

    S. L. Peake

  26. Northern Clinical School, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    A. Delaney

Authors
  1. D. C. Angus
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  2. A. E. Barnato
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  3. D. Bell
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  4. R. Bellomo
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  8. A. Delaney
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  9. D. A. Harrison
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  15. S. L. Peake
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  19. M. Singer
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  20. S. A. R. Webb
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  21. L. A. Weissfeld
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  23. J. D. Young
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Corresponding author

Correspondence to S. L. Peake.

Additional information

For the ARISE, ProCESS, ProMISe and PRISM Investigators.

Take-home message: EGDT for patients presenting to the ED with early septic shock does not decrease mortality but does increase ICU resource utilisation.

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Angus, D.C., Barnato, A.E., Bell, D. et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med 41, 1549–1560 (2015). https://doi.org/10.1007/s00134-015-3822-1

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  • DOI: https://doi.org/10.1007/s00134-015-3822-1

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