A Real-World Analysis of Hydrocortisone and Fludrocortisone Prescribing in Surgical Patients with Septic Shock

Background: Corticosteroid use in septic shock remains controversial, with trials showing conflicting results. Most studies have been conducted in mixed medical–surgical populations, limiting generalizability to surgical patients who face unique risks. We examined how timing of steroid administration affects outcomes in surgical intensive care unit patients with septic shock. Methods: In this retrospective cohort study, we analyzed data from 13,512 surgical patients with septic shock using the TriNetX platform. Patients were categorized into four cohorts: no steroids (n = 8,180), any steroid therapy (n = 5,332), early therapy (≤24 h, n = 2,911), and late therapy (>24 h, n = 2,421). We conducted propensity-matched analyses examining 90-day mortality, infectious complications, and surgical complications. Results: Early steroid administration was associated with lower 90-day mortality compared with no steroids (31.5% vs. 33.3%; hazard ratio HR: 0.74; 95% confidence interval CI: 0.62–0.88; p = 0.006), whereas late administration correlated with higher mortality (34.1% vs. 27.1%; HR: 1.26; 95% CI: 1.11–1.43; p < 0.001). Steroids were associated with lower rates of surgical site infections (relative risk RR: 0.63; p = 0.032) and wound dehiscence (RR: 0.73; p = 0.019), but higher rates of pneumonia (RR: 1.22; p = 0.003), myopathy (RR: 2.25; p < 0.001), and bowel ischemia (RR: 2.29; p = 0.008). Conclusions: In surgical ICU patients with septic shock, the timing of steroid administration impacts outcomes. Early administration was associated with reduced mortality, whereas late administration correlated with increased mortality. Steroids demonstrated a complex profile of beneficial and adverse effects on post-surgical complications. These findings highlight the importance of timing of therapy in surgical septic shock and may help explain conflicting results from previous trials in mixed populations.