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Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis

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Abstract

Purpose

To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.

Methods

We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.

Results

There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89–1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91–1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90–1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03–2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) −1.52 days; 95% CI −1.71 to −1.32, p < 0.0001], duration of mechanical ventilation (MD −1.38 days; 95% CI −1.96 to −0.80, p < 0.0001), and ICU stay (MD −0.75 days; 95% CI −1.34 to −0.17, p = 0.01) were shorter with corticosteroids versus placebo.

Conclusions

In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced.

PROSPERO registration no. CRD42017084037.

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Acknowledgements

We would like to thank Agnes Wroblewski from the Douglas Piper Medical Library at RNSH for her assistance in obtaining elusive manuscripts included in this review. We are indebted to Dr Arne Andreasen, and Dr Soo Wan Kim for providing translations. We are deeply appreciative of Professors Annane, Arabi, Bollaert, Briegel, Gordon, Meduri, Sprung, and Torres, and Drs Cicarelli, Mirea, Rinaldi, Tongyoo, Gabarus-Barri for supplying additional details and clarifications regarding their studies.

Funding

This study received no funding.

Author information

Authors and Affiliations

  1. Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Sofie Louise Rygård, Anders Granholm, Morten Hylander Møller & Anders Perner

  2. University of New South Wales, Kensington, NSW, Australia

    Ethan Butler & John Myburgh

  3. Centre for Research in Intensive Care, Copenhagen, Denmark

    Morten Hylander Møller & Anders Perner

  4. Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Jeremy Cohen

  5. University of Queensland, Brisbane, QLD, Australia

    Jeremy Cohen & Balasubramanian Venkatesh

  6. Division of Critical Care and Trauma, The George Institute for Global Health, University of New South Wales, Sydney, Australia

    Simon Finfer & John Myburgh

  7. Department of Intensive Care Medicine, St. George Hospital, Kogarah, NSW, Australia

    John Myburgh

  8. Department of Intensive Care, Wesley Hospital, Brisbane, QLD, Australia

    Balasubramanian Venkatesh

  9. Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, St. Leonards, NSW, 2065, Australia

    Simon Finfer & Anthony Delaney

  10. Northern Clinical School, Sydney Medical School, University of Sydney, St. Leonards, NSW, Australia

    Anthony Delaney

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  1. Sofie Louise Rygård
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  2. Ethan Butler
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Corresponding author

Correspondence to Anthony Delaney.

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Conflicts of interest

Professors Venkatesh, Finfer, Myburgh, Perner and Associate Professor Cohen were all members of the management committee of the ADRENAL study. The other authors have no conflicts of interest to declare.

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Rygård, S.L., Butler, E., Granholm, A. et al. Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 44, 1003–1016 (2018). https://doi.org/10.1007/s00134-018-5197-6

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  • DOI: https://doi.org/10.1007/s00134-018-5197-6

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