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    Original Investigation
    December 21, 2018

    Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1West China Hospital, Sichuan University, Chengdu, Sichuan, China
    • 2Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
    • 3Chinese University of Hong Kong, Shenzhen, Guangdong, China
    • 4University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
    • 5Longquanyi Hospital, Chengdu, Sichuan, China
    • 6Southwest Hospital, Army Medical University, Chongqing, China
    • 7Sichuan University Library, Chengdu, Sichuan, China
    JAMA Intern Med. 2019;179(2):213-223. doi:10.1001/jamainternmed.2018.5849
    Key Points

    Question  Are corticosteroids associated with a reduction in 28-day mortality in patients with sepsis?

    Findings  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.

    Meaning  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.


    Importance  Although corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear.

    Objective  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  Twenty-eight–day mortality.

    Results  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.