Improved 28-day mortality with the use of steroids in sepsis

Reference

Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis. JAMA Intern Med 2018 Dec 21. doi: 10.1001/jamainternmed.2018.5849. [Epub ahead of print]

Synopsis

These investigators searched MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials, as well as a clinical trial registry and conference proceedings to find randomized controlled trials (RCTs) that evaluated the effect of steroids on 28-day mortality on adult patients with sepsis or septic shock. Two authors independently selected studies for inclusion, extracted data, and performed an assessment of the risk of bias and the quality of evidence of included studies. Ultimately, 37 RCTs with 9564 total patients were included: 11 had a low risk of bias, 12 had an unclear risk, and 14 had a high risk. Thirty-four trials reported on 28-day mortality, showing a reduction of death with the use of steroids (26.3% vs 29.2%; relative risk [RR] 0.90; 95% CI 0.82 - 0.98) and significant improvement in both in-hospital mortality (RR 0.88; 0.79 - 0.99) and ICU mortality (RR 0.85; 0.77 - 0.94). Steroids were also associated with an increase in shock reversal and vasopressor-free days and a decrease in ICU length of stay and time to resolution of shock. In the 3 trials that examined this outcome, there was no difference detected in 90-day mortality. Hyperglycemia and hypernatremia were increased in the steroid group, but severe adverse events, including gastrointestinal bleeding and infection, did not differ. One limitation of this meta-analysis is the presence of significant clinical heterogeneity due to the different formulations and doses of steroids used and the different timing and duration of therapy, especially given that a few of the included studies were published in the 1970s and 1980s. Publication bias was also detected, but this may be a result of smaller studies in the overall analysis. Sensitivity analyses that excluded older studies and smaller studies still confirmed the findings of the primary outcome.