Pre-Emptive Hydrocortisone Therapy in Early Septic Shock: A Double-Blind, Allocation-Concealed, Pilot Randomized Controlled Trial Publisher



E Emami EHSAN ; E Molaei EMAD ; S Fattah Ghazi SAMRAND ; M Sohrabi MARJAN ; H Khalili HOSSEIN
Source: DARU, Journal of Pharmaceutical Sciences Published:2025

Abstract

Background: Sepsis, a major global health issue, often progresses to septic shock with high morbidity and mortality. Corticosteroids especially low-dose hydrocortisone have shown promise in septic shock management. However, the role of hydrocortisone as pre-emptive therapy in early septic shock remains unclear. Objective: This study investigates the effects of pre-emptive administration of low-dose, short-course hydrocortisone on outcomes in patients with early septic shock. Methods: A double-blind, randomized controlled trial was conducted, enrolling individuals with early septic shock. Patients were randomized to receive either low-dose, short-course hydrocortisone (50 mg every 6 h for 48 h) as pre-emptive therapy or usual care. The primary outcome was vasopressor requirement. Results: Pre-emptive low-dose, short-course hydrocortisone significantly reduced the duration of vasopressor therapy (P = 0.03), cumulative vasopressor dose (38.52 mg vs. 99.11 mg, P = 0.02), and the necessity for mechanical ventilation (10% vs. 40%, P = 0.02). The hydrocortisone group exhibited a lower incidence of septic shock (20% vs. 40%), although this difference was not statistically significant (P = 0.17). No significant differences were observed in mortality rates (2 deaths per group), Sequential Organ Failure Assessment (SOFA) scores (P = 0.29), or ICU length of stay (P = 0.66). Serious adverse events were comparable between the two groups. Conclusions: Although pre-emptive hydrocortisone did not change the progression from early septic shock to septic shock, it significantly reduced both the duration of vasopressor therapy and the cumulative vasopressor dose in patients who entered the shock phase, without any significant adverse events. © 2025 Elsevier B.V., All rights reserved.