Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study

Background: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. Objective: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. Methods: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. Results: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). Conclusion and Relevance: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.