Rapid uptake of adjunctive corticosteroids for critically ill adults with septic shock following publication of ADRENAL trial. A multicenter, retrospective analysis of prescribing practices in Queensland Intensive Care Units

Abstract

Septic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. A retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. We included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 μg/kg/min (IQR 0.02-0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition, and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (-0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14-1.77; p = 0.0015 and OR 2.03; 95% CI 1.74-2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect -0.81; 95% CI 0.65-0.99; p = 0.044). Publication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality.