ARDS and Corticosteroids: Beyond COVID-19

Abstract Acute respiratory distress syndrome (ARDS) remains a high‑mortality condition despite major advances in ventilatory and supportive care. Because lung injury is driven by uncontrolled inflammation and disruption of the alveolar–capillary barrier, corticosteroids have long been considered a biologically plausible therapy. Over several decades, randomized trials have evaluated different corticosteroid types, doses, durations, and initiation timings in heterogeneous populations, including patients with primary ARDS and those with sepsis or pneumonia complicated by ARDS. The COVID‑19 pandemic provided a unique opportunity to study a more homogeneous cause of ARDS, generating additional evidence supporting corticosteroid efficacy in virus‑related respiratory failure. Despite these advances, clinical practice remains variable worldwide. Evolving definitions, diverse trial designs, and etiologic variability have led to uncertainty regarding indication, optimal dosing, drug selection, and treatment duration. The new global definition of ARDS now includes patients supported with noninvasive ventilation or high‑flow nasal oxygen, raising questions about how evidence derived from invasively ventilated populations applies to these groups. Parallel research identifying inflammatory subphenotypes with potentially divergent treatment responses further underscores the need for individualized, evidence‑based strategies. In this review, we examine conceptual, biological, and clinical considerations and synthesize the available evidence to inform decision‑making. We propose a pragmatic, context‑based framework to guide corticosteroid use in ARDS according to etiology and patient characteristics, emphasizing early initiation—ideally within 24–48 hours—and regimens equivalent to ≥80 mg/day of methylprednisolone or ≥400 mg/day of hydrocortisone for at least seven days, which have demonstrated efficacy with an acceptable safety profile. Research priorities include optimizing dose and duration, evaluating non‑ventilated and underrepresented subgroups, and clarifying phenotype‑specific effects and long‑term safety.