Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis.

Abstract

The benefit-risk profile of systemic corticosteroids in non-COVID-19 pneumonia and acute respiratory distress syndrome (ARDS) remains debated. To assess corticosteroid effects on mortality and infection-related complications in adults with severe pneumonia or ARDS. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform through September 2025. Randomized controlled trials comparing systemic corticosteroids with placebo and usual care. Primary analysis: severe pneumonia or ARDS with corticosteroids 3 mg/kg^-1 of body weight per day^-1 or less (prednisone-equivalent) for 15 days or less, initiated within 7 days. Paired reviewers; consensus for disagreements. From 16 831 screened records, 20 studies (15 severe pneumonia, 5 ARDS) including 3459 participants met criteria. Low-dose, short-course corticosteroids probably reduce short-term mortality in severe pneumonia (15 studies, 2445 participants; risk ratio [RR], 0.73 [95% CI, 0.57 to 0.93]; <i>I</i> ²= 14%; moderate certainty) and ARDS (5 studies, 1014 participants; RR, 0.77 [CI, 0.61 to 0.99]; <i>I</i> ²= 23%; moderate certainty). Corticosteroids may reduce secondary shock in severe pneumonia (9 studies, 1690 participants; RR, 0.49 [CI, 0.26 to 0.92]; <i>I</i> ²= 55%; low certainty). They probably result in little to no difference in hospital-acquired infections (severe pneumonia: 7 studies, 1665 participants; RR, 0.99 [CI, 0.82 to 1.20]; <i>I</i> ²= 0%; moderate certainty; ARDS: 4 studies, 677 participants; RR, 0.97 [CI, 0.59 to 1.59]; <i>I</i> ²= 0%; low certainty) or secondary pneumonia (severe pneumonia: 4 studies, 1011 participants; RR, 0.96 [CI, 0.66 to 1.39]; <i>I</i> ²= 0%; ARDS: 4 studies, 677 participants; RR, 0.88 [CI, 0.43 to 1.79]; <i>I</i> ²= 0%; both low certainty). Evidence is very uncertain for catheter-related and bloodstream infections. Long-term mortality evidence is very uncertain for severe pneumonia. Heterogeneous pneumonia severity classification limiting subgroup precision. In severe pneumonia and ARDS, adjunct corticosteroids probably reduce short-term mortality. In severe pneumonia, they may reduce secondary shock. In both conditions, corticosteroids may have little or no effect on hospital-acquired infections. None. (PROSPERO: CRD42024536301).