Adjunct corticosteroids likely reduce short-term mortality in severe non-COVID-19 pneumonia

1. In this systematic review and meta-analysis, adjunct corticosteroids likely reduce short-term mortality in patients with severe non-COVID-19 pneumonia and acute respiratory distress syndrome.

2. Corticosteroids appear to have little to no impact on hospital-acquired infections or secondary pneumonia in both severe pneumonia and acute respiratory distress syndrome.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Severe pneumonia can progress to acute respiratory distress syndrome (ARDS), necessitating mechanical ventilation and multi-organ support. The role of corticosteroids as adjunct therapy in pneumonia remains controversial. Although randomized trials in COVID-19 pneumonia have shown mortality benefits with short courses of low-dose corticosteroids, studies in non-COVID-19 pneumonia have not demonstrated similar effects. Concerns also persist regarding immunosuppression and the potential for increased secondary infections, particularly in ARDS, which is commonly secondary to bacterial infection. This systematic review evaluated the impact of corticosteroid therapy on mortality and infectious complications in severe non-COVID-19 pneumonia or ARDS. Twenty studies met inclusion criteria. Most pneumonia studies raised concerns for bias, whereas ARDS studies were generally of higher quality with lower risk of bias. Overall, low-dose, short-course corticosteroids likely reduce short-term mortality in both severe pneumonia and ARDS, although effects on long-term mortality remain uncertain due to limited data. Corticosteroids may also reduce secondary shock in severe pneumonia and appear to have little to no association with hospital-acquired infections or secondary pneumonia. Considerable uncertainty persists regarding their effect on catheter-related infections and bacteremia. Corticosteroids were associated with increased hyperglycemia in both conditions and with gastrointestinal bleeding in ARDS. Generalizability is limited by heterogeneity in pneumonia severity definitions, which may affect subgroup precision. Nevertheless, current evidence suggests that corticosteroids may reduce short-term mortality in severe pneumonia and ARDS and may decrease secondary shock in severe pneumonia, although further research is needed to clarify optimal timing and dosing.

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Relevant Reading: Corticosteroids for Severe Pneumonia and Acute Respiratory Distress Syndrome: From “Yes or No” to “Who, When, and How”

In-Depth [systematic review and meta-analysis]: This study evaluated the association between corticosteroid use, mortality, and infectious complications in adults hospitalized with non-COVID-19 pneumonia or ARDS. The intervention was low-dose corticosteroid therapy. Populations were categorized as severe pneumonia, non-severe pneumonia, or ARDS. Studies were excluded if they focused solely on COVID-19, influenza pneumonia, drug-induced pulmonary toxicity, COPD exacerbations, or immunocompromised patients. Primary outcomes included short-term mortality (within 90 days), long-term mortality (beyond 6 months), and infection-related complications, including hospital-acquired infections, secondary pneumonia, bloodstream infections, catheter-related infections, and secondary shock. Secondary outcomes included ventilation and hospitalization metrics, time to clinical cure, and safety outcomes. Twenty studies (3,459 participants) met inclusion criteria: 15 examined severe pneumonia, and 5 examined ARDS. In severe pneumonia, 3 studies were low risk of bias, 7 had some concerns, and 5 were high risk; in ARDS, 3 were low risk, 1 had some concerns, and 1 was high risk. Corticosteroids likely reduce short-term mortality in severe pneumonia (15 studies, 2,445 participants; risk ratio [RR], 0.73; 95% confidence interval [CI], 0.57 to 0.93; moderate certainty) and in ARDS (5 studies, 1,014 participants; RR, 0.77; 95% CI, 0.61 to 0.99; moderate certainty), with sensitivity and subgroup analyses consistent across shock status, corticosteroid type, ICU setting, dose, treatment duration, and baseline oxygen requirement. Evidence for long-term mortality was very uncertain, with only one severe pneumonia study reporting 180-day mortality (RR, 0.76; 95% CI, 0.64 to 0.91) and no ARDS data. In severe pneumonia, corticosteroids reduced secondary shock (9 studies, 1,690 participants; RR, 0.49; 95% CI, 0.26 to 0.92) and decreased need for invasive ventilation, incidence of respiratory failure, and ICU length of stay. Corticosteroids had minimal effect on hospital-acquired infections (severe pneumonia: RR, 0.99; 95% CI, 0.82 to 1.20; ARDS: RR, 0.97; 95% CI, 0.59 to 1.59) or secondary pneumonia (severe pneumonia: RR, 0.96; 95% CI, 0.66 to 1.39; ARDS: RR, 0.88; 95% CI, 0.43 to 1.79). Overall, low-dose corticosteroids may reduce short-term mortality in severe pneumonia and ARDS, though further research is needed to clarify optimal timing, dosing, and long-term outcomes.

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