BACKGROUND AND PURPOSE:

• Corticosteroids has been used for decades to treat sepsis
• In this update to a 2004 Cochrane review, Annane et al. (Cochrane Systematic Reviews, 2019) assessed the effects of corticosteroids on death in children and adults with sepsis

METHODS:

• Systematic review and meta-analysis
• Data sources
  • CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, ISRCTN, and the WHO Clinical Trials Search Portal
  • Unpublished data from the authors of some trials were obtained
• Inclusion criteria
  • RCTs that included:  Corticosteroids versus placebo or usual care (antimicrobials, fluid replacement, and vasopressor therapy as needed) in children and adults with sepsis | Continuous infusion versus intermittent bolus of corticosteroids
• Study design and data analysis
  • All review authors screened and selected studies for inclusion
  • One author extracted data, which was checked by the others, and by the lead author of the primary study when possible
  • The methodological quality of trials was assessed using Grade criteria

RESULTS:

• Total of 61 trials | 12,192 participants
  • Participants (children vs adults): 6 only children | 2 with both children and adults | Remainder adults only
  • 9 studies ongoing (to be reviewed in the future)
  • 19 trials were judged as being at low risk of bias

Corticosteroids Versus Placebo or Usual Care

• Corticosteroids probably results in reduced 28-day mortality
  • Risk ratio (RR) 0.91 (95% CI, 0.84 to 0.99; moderate-certainty evidence)
• Corticosteroids may result in little to no difference in long-term mortality
  • RR 0.97 (95% CI, 0.91 to 1.03; low-certainty evidence)
• Corticosteroids probably slightly reduce hospital mortality
  • RR 0.90 (95% CI, 0.82 to 0.99; moderate-certainty evidence)
• Corticosteroids reduced length of ICU stay
  • mean difference (MD) -1.07 days (95% CI, -1.95 to -0.19; high-certainty evidence)
• Corticosteroids resulted in a reduction in length of hospital stay for all participants
  • MD -1.63 days (95% CI, -2.93 to -0.33; high-certainty evidence)
• Risks associated with corticosteroids
  • Increased risk for muscle weakness: RR 1.21 (95% CI, 1.01 to 1.44; high-certainty evidence)
  • Increased risk for hypernatremia: RR 1.66 (95% CI, 1.34 to 2.06; high-certainty evidence
  • Probable increase for hyperglycemia: RR 1.20 (95% CI, 1.10 to 1.31; moderate-certainty evidence)
• Study did not find an increased risk for the following
  • Superinfection | Gastroduodenal bleeding | Stroke | Cardiac events | Neuropsychiatric events

Continuous Infusion of Corticosteroids vs Intermittent Bolus

• Uncertain effects of continuous infusion vs intermittent bolus administration (certainty of evidence for all outcomes was very low)

Subgroup Analysis

• Age: No difference based on child vs adult
• Severity of sepsis: Septic shock, ARDS and community‐acquired pneumonia more likely to derive a survival benefit than less severe sepsis (barely statistically significant)

CONCLUSION:

• The use of corticosteroids probably reduces 28-day and hospital mortality for patients with sepsis
  • There may not be a difference in long-term mortality
• Corticosteroid treatment resulted in reductions in ICU and hospital length of stay
• The authors recognize that recent studies show benefit of corticosteroids on shock reversal (hemodynamic stability ≤24 hours) in patients with septic shock
  • However, this present systematic review included trial data that were not previously included (non-English or non-published)
  • This study may not have found the same benefit due to inclusion of “qualitatively and quantitatively better data than were provided previously”

Learn More – Primary Sources:

Corticosteroids for treating sepsis in children and adults

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