Steroid administration, timing, and dose in patients with septic shock in the emergency department: retrospective analysis of a multicenter prospective cohort study.

The benefit and optimal timing of corticosteroids in septic shock remain debated. Most evidence comes from intensive care unit-based studies, although key treatment decisions are often made early in the emergency department (ED). This study evaluated the association between steroid administration, including hydrocortisone timing and dose, and mortality in patients with septic shock in the ED. This retrospective observational study used an ED-based prospective multicenter septic shock registry from the Korean Shock Society (KoSS). The association between steroid administration and 28-day mortality was evaluated in adult patients with septic shock using multivariable regression models. Among hydrocortisone-treated patients, the associations of time from first vasopressor initiation to first hydrocortisone administration, norepinephrine-equivalent dose, and hydrocortisone dose with mortality were analyzed. From 2015 to 2023, a total of 5,127 patients were included. After adjustment, steroid use was associated with lower 28-day mortality (steroid: adjusted odds ratio [aOR] 0.752, 95% confidence interval [CI] 0.637-0.887; hydrocortisone: aOR 0.745, 95% CI 0.627-0.884; both p = 0.001). Multivariable analyses after PSM, IPTW, multivariable Cox proportional hazards models, and multivariable time-dependent Cox proportional hazards models showed similar findings. This association remained in the vasopressin subgroup (aOR 0.631, 95% CI 0.494-0.805, p < 0.001) but not in patients who did not receive vasopressin (aOR 0.967, 95% CI 0.773-1.209, p = 0.769; interaction p = 0.025). Among 1,529 patients with septic shock who received hydrocortisone, a higher norepinephrine-equivalent dose at first steroid administration (aOR 2.014, 95% CI 1.302-3.114, p = 0.002) and a longer interval from first vasopressor initiation to first steroid administration (aOR 1.018, 95% CI 1.003-1.033, p = 0.017) were associated with increased mortality, as was hydrocortisone dosing > 300 mg/day (aOR 1.577, 95% CI 1.179-2.110, p = 0.002). In this multicenter ED-based registry, steroid administration in the ED was associated with lower 28-day mortality among patients with septic shock, particularly those receiving vasopressin. Among hydrocortisone-treated patients, higher norepinephrine-equivalent dose at hydrocortisone initiation, a longer interval from vasopressor initiation to hydrocortisone administration, and hydrocortisone dose > 300 mg/day were associated with increased mortality; however, these findings should be interpreted cautiously as observational and hypothesis-generating.