Corticosteroids in the treatment of severe sepsis and septic shock in adults

A systematic review

Djillali Annane, Eric Bellissant, Pierre Edouard Bollaert, Josef Briegel, Marco Confalonieri, Raffaele De Gaudio, Didier Keh, Yizhak Kupfer, Michael Oppert, Gianfranco Meduri

Research output: Contribution to journalReview article

376 Citations (Scopus)

Abstract

Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results: We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I 2 =53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P=.02; I 2 =4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P<.001; I 2 =0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P=.50; I 2 =0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P=.92; I 2 =8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P=.58; I 2 =30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P<.001; I 2 =0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P<.001; I 2 =0%). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

Original languageEnglish (US)
Pages (from-to)2362-2375
Number of pages14
JournalJAMA - Journal of the American Medical Association
Volume301
Issue number22
DOIs
StatePublished - Jun 10 2009

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Septic Shock
Sepsis
Adrenal Cortex Hormones
Confidence Intervals
Odds Ratio
Mortality
Therapeutics
Hypernatremia
Systemic Inflammatory Response Syndrome
Superinfection
Information Storage and Retrieval
MEDLINE
Hyperglycemia
Intensive Care Units
Meta-Analysis
Shock
Length of Stay
Placebos
Databases
Hemorrhage

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Corticosteroids in the treatment of severe sepsis and septic shock in adults : A systematic review. / Annane, Djillali; Bellissant, Eric; Bollaert, Pierre Edouard; Briegel, Josef; Confalonieri, Marco; De Gaudio, Raffaele; Keh, Didier; Kupfer, Yizhak; Oppert, Michael; Meduri, Gianfranco.

In: JAMA - Journal of the American Medical Association, Vol. 301, No. 22, 10.06.2009, p. 2362-2375.

Research output: Contribution to journalReview article

Annane, D, Bellissant, E, Bollaert, PE, Briegel, J, Confalonieri, M, De Gaudio, R, Keh, D, Kupfer, Y, Oppert, M & Meduri, G 2009, 'Corticosteroids in the treatment of severe sepsis and septic shock in adults: A systematic review', JAMA - Journal of the American Medical Association, vol. 301, no. 22, pp. 2362-2375. https://doi.org/10.1001/jama.2009.815
Annane, Djillali ; Bellissant, Eric ; Bollaert, Pierre Edouard ; Briegel, Josef ; Confalonieri, Marco ; De Gaudio, Raffaele ; Keh, Didier ; Kupfer, Yizhak ; Oppert, Michael ; Meduri, Gianfranco. / Corticosteroids in the treatment of severe sepsis and septic shock in adults : A systematic review. In: JAMA - Journal of the American Medical Association. 2009 ; Vol. 301, No. 22. pp. 2362-2375.
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title = "Corticosteroids in the treatment of severe sepsis and septic shock in adults: A systematic review",
abstract = "Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results: We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3{\%}) vs 400/1039 (38.5{\%}) in randomized trials (risk ratio [RR], 0.84; 95{\%} confidence interval [CI], 0.71-1.00; P=.05; I 2 =53{\%} by random-effects model) and 28/121 (23.1{\%}) vs 24/125 (19.2{\%}) in quasi-randomized trials (RR, 1.05, 95{\%} CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5{\%}) vs 264/599 (44{\%}) (RR, 0.84; 95{\%} CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9{\%}] vs 276/471 [58.6{\%}]; RR, 1.12; 95{\%} CI, 1.02-1.23; P=.02; I 2 =4{\%}) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95{\%} CI, -7.04 to -1.94; P<.001; I 2 =0{\%}) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1{\%}] vs 56/764 [7.3{\%}]; P=.50; I 2 =0{\%}), superinfection (14 trials; 184/998 [18.4{\%}] vs 170/950 [17.9{\%}]; P=.92; I 2 =8{\%}), or neuromuscular weakness (3 trials; 4/407 [1{\%}] vs 7/404 [1.7{\%}]; P=.58; I 2 =30{\%}). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6{\%}] vs 308/670 [46{\%}]; P<.001; I 2 =0{\%}) and hypernatremia (3 trials; 127/404 [31.4{\%}] vs 77/401 [19.2{\%}]; P<.001; I 2 =0{\%}). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.",
author = "Djillali Annane and Eric Bellissant and Bollaert, {Pierre Edouard} and Josef Briegel and Marco Confalonieri and {De Gaudio}, Raffaele and Didier Keh and Yizhak Kupfer and Michael Oppert and Gianfranco Meduri",
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language = "English (US)",
volume = "301",
pages = "2362--2375",
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TY - JOUR

T1 - Corticosteroids in the treatment of severe sepsis and septic shock in adults

T2 - A systematic review

AU - Annane, Djillali

AU - Bellissant, Eric

AU - Bollaert, Pierre Edouard

AU - Briegel, Josef

AU - Confalonieri, Marco

AU - De Gaudio, Raffaele

AU - Keh, Didier

AU - Kupfer, Yizhak

AU - Oppert, Michael

AU - Meduri, Gianfranco

PY - 2009/6/10

Y1 - 2009/6/10

N2 - Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results: We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I 2 =53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P=.02; I 2 =4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P<.001; I 2 =0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P=.50; I 2 =0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P=.92; I 2 =8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P=.58; I 2 =30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P<.001; I 2 =0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P<.001; I 2 =0%). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

AB - Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results: We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I 2 =53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P=.02; I 2 =4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P<.001; I 2 =0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P=.50; I 2 =0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P=.92; I 2 =8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P=.58; I 2 =30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P<.001; I 2 =0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P<.001; I 2 =0%). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

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