Are corticosteroids associated with a reduction in 28-day mortality in patients with sepsis?
In this systematic review and meta-analysis of 37 randomized clinical trials that included 9564 patients with sepsis, administration of corticosteroids was associated with reduced 28-day mortality. Corticosteroids were also significantly associated with increased shock reversal at day 7 and vasopressor-free days and with decreased intensive care unit length of stay, the Sequential Organ Failure Assessment score at day 7, and time to resolution of shock.
The findings suggest that administration of corticosteroid treatment in patients with sepsis is associated with significant improvement in health care outcomes and thus with reduced 28-day mortality.
Although corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear.
To conduct a systematic review and meta-analysis of the efficacy and safety of corticosteroids in patients with sepsis.
Data Sources and Study Selection
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until March 20, 2018, and updated on August 10, 2018. The terms corticosteroids, sepsis, septic shock, hydrocortisone, controlled trials, and randomized controlled trial were searched alone or in combination. Randomized clinical trials (RCTs) were included that compared administration of corticosteroids with placebo or standard supportive care in adults with sepsis.
Data Extraction and Synthesis
Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data abstraction, and risk assessment.
Main Outcomes and Measures
This meta-analysis included 37 RCTs (N = 9564 patients). Eleven trials were rated as low risk of bias. Corticosteroid use was associated with reduced 28-day mortality (RR, 0.90; 95% CI, 0.82-0.98; I2 = 27%) and intensive care unit (ICU) mortality (RR, 0.85; 95% CI, 0.77-0.94; I2 = 0%) and in-hospital mortality (RR, 0.88; 95% CI, 0.79-0.99; I2 = 38%). Corticosteroids were significantly associated with increased shock reversal at day 7 (MD, 1.95; 95% CI, 0.80-3.11) and vasopressor-free days (MD, 1.95; 95% CI, 0.80-3.11) and with ICU length of stay (MD, −1.16; 95% CI, −2.12 to −0.20), the sequential organ failure assessment score at day 7 (MD, −1.38; 95% CI, −1.87 to −0.89), and time to resolution of shock (MD, −1.35; 95% CI, −1.78 to −0.91). However, corticosteroid use was associated with increased risk of hyperglycemia (RR, 1.19; 95% CI, 1.08-1.30) and hypernatremia (RR, 1.57; 95% CI, 1.24-1.99).
Conclusions and Relevance
The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.
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Fang F, Zhang Y, Tang J, et al. Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis: A Systematic Review and Meta-analysis. JAMA Intern Med. Published online December 21, 2018. doi:10.1001/jamainternmed.2018.5849
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