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Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis

BMJ 2004; 329 doi: (Published 26 August 2004) Cite this as: BMJ 2004;329:480
  1. Djillali Annane, professor of intensive care medicine (djillali.annane{at},
  2. Eric Bellissant, professor of clinical pharmacology2,
  3. Pierre Edouard Bollaert, professor of intensive care medicine3,
  4. Josef Briegel, professor of anaesthesiology and intensive care medicine4,
  5. Didier Keh, attending physician5,
  6. Yizhak Kupfer, attending physician6
  1. 1 Critical Care Department, Université de Versailles Saint-Quentin en Yvelines, Assistance Publique-Hôpitaux de Paris, Hôpital Raymond Poincaré, Garches 92380, France
  2. 2 Clinical Investigation Centre, INSERM 0203, Université de Rennes 1, Centre Hospitalier Universitaire, Hôpital de Pontchaillou, Rennes 35033, France
  3. 3 Critical Care Department, Université de Nancy 1, Centre Hospitalier Universitaire, Hôpital Central, Nancy 54000, France
  4. 4 Institut für Anaesthesiology, Klinikum der Universität München, Munich, 81366, Germany
  5. 5 Intensive Care Unit, Charité-Campus Virchow Clinic, Berlin, 13353, Germany
  6. 6 Division of Pulmonary and Critical Care Medicine, Maimonides Medical Centre, Brooklyn, New York, NY 11219, USA
  1. Correspondence to: D Annane
  • Accepted 16 June 2004


Objective To assess the effects of corticosteroids on mortality in patients with severe sepsis and septic shock.

Data sources Randomised and quasi-randomised trials of corticosteroids versus placebo (or supportive treatment alone) retrieved from the Cochrane infectious diseases group's trials register, the Cochrane central register of controlled trials, Medline, Embase, and LILACS.

Review method Two pairs of reviewers agreed on eligibility of trials. One reviewer entered data on to the computer and four reviewers checked them. We obtained some missing data from authors of trials and assessed methodological quality of trials.

Results 16/23 trials (n = 2063) were selected. Corticosteroids did not change 28 day mortality (15 trials, n = 2022; relative risk 0.92, 95% confidence interval 0.75 to 1.14) or hospital mortality (13 trials, n = 1418; 0.89, 0.71 to 1.11). There was significant heterogeneity. Subgroup analysis on long courses (≥ 5 days) with low dose (≤ 300 mg hydrocortisone or equivalent) corticosteroids showed no more heterogeneity. The relative risk for mortality was 0.80 at 28 days (five trials, n = 465; 0.67 to 0.95) and 0.83 at hospital discharge (five trials, n = 465, 0.71 to 0.97). Use of corticosteroids reduced mortality in intensive care units (four trials, n = 425, 0.83, 0.70 to 0.97), increased shock reversal at 7 days (four trials, n = 425; 1.60, 1.27 to 2.03) and 28 days (four trials, n = 425, 1.26, 1.04 to 1.52) without inducing side effects.

Conclusions For all trials, regardless of duration of treatment and dose, use of corticosteroids did not significantly affect mortality. With long courses of low doses of corticosteroids, however, mortality at 28 days and hospital morality was reduced.


  • A longer version of this review has been published in the Cochrane Library.37

  • Contributors All authors were involved in study concept, design, and critical revision for important intellectual content. DA, PEB, JB, DK, and YK were responsible for acquisition of data. DA, PEB, JB, and DK analysed and interpreted the data. DA and EB drafted the review. DA is guarantor.

  • Funding Hôpital Raymond Poincaré, Garches, France. UK Department for International Development.

  • Competing interests Authors of this review have been involved in randomised controlled trials of low dose hydrocortisone that are included in this review.

  • Ethical approval Not required.

  • Accepted 16 June 2004
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