Systemic corticosteroids in critical illness: an evidence-based framework for clinical decision-making

Systemic corticosteroids are pivotal in managing inflammation-driven critical illnesses, yet bedside translation remains inconsistent. This systematic review establishes an evidence-based framework for clinical decision-making by horizontally synthesizing contemporary evidence across severe community-acquired pneumonia (sCAP), acute respiratory distress syndrome (ARDS), and septic shock.

A systematic electronic search was conducted across PubMed, EMBASE, and the Cochrane Library up to early 2026. Peer-reviewed randomized controlled trials (RCTs), systematic reviews, and meta-analyses published in English were eligible. Data regarding population characteristics, dosing regimens, initiation timing, duration, and safety profiles were independently extracted and qualitatively synthesized.

Landmark trials define context-dependent efficacy: early hydrocortisone continuous infusion significantly reduces 28-day mortality in sCAP (CAPE COD), while a 10-day dexamethasone regimen improves ventilator-free days and survival in moderate-to-severe ARDS (DEXA-ARDS). In septic shock, early hydrocortisone-fludrocortisone combination accelerates shock resolution and lowers 90-day mortality (APROCCHS). These outcomes align with distinct pharmacological profiles: hydrocortisone provides dual glucocorticoid/mineralocorticoid activity to restore vascular tone, whereas dexamethasone exerts potent transrepression of proinflammatory transcription factors. To mitigate steroid-induced harm, protocolized safety targets are essential, including maintaining blood glucose at 140-180 mg/dL and actively monitoring for secondary infections.

Corticosteroids do not exert a uniform class effect. Bedside success requires personalized, protocolized regimens optimized by scenario-specific timing, dosing, and proactive adverse-event monitoring.