Comparing Vasopressin and Hydrocortisone as Adjunctive Measures in Septic Shock

Background: Norepinephrine has been widely established as the first-line agent for hemodynamic support in septic shock. The timing and order of initiation of vasopressin and hydrocortisone as adjunctive agents remains highly debated, with recent literature suggesting lower mortality with early hydrocortisone initiation. Objective: The aim of the study was to evaluate the effectiveness and safety of vasopressin compared to hydrocortisone as adjuncts to norepinephrine in septic shock. Methods: This was a multicenter, retrospective, observational study conducted in adult patients with septic shock admitted to the intensive care unit (ICU) between February 2020 and July 2023. Patients were divided into 2 cohorts based on the initial adjunctive agent administered following norepinephrine initiation: vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day). Individuals who received both study drugs within 6 hours of each other were excluded. The primary outcome was in-hospital mortality. Secondary outcomes included ICU length of stay (LOS), hospital LOS, time to vasopressor discontinuation, renal replacement therapy (RRT) initiation, and safety outcomes. Results: A total of 628 patients were included: 193 patients (30.7%) received hydrocortisone, and 435 patients (69.3%) received vasopressin. Hydrocortisone was associated with lower in-hospital mortality (53.3% vs. 37.3%, adjusted hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.19-2.74, P = 0.006). Shorter hospital LOS and lower RRT initiation were observed with hydrocortisone. A longer time to initiation of the initial adjunctive agent was associated with an increased risk of in-hospital mortality (HR 1.08, 95% CI 1.04-1.11, P < 0.001). Conclusion and Relevance: Administration of hydrocortisone as an adjunct to norepinephrine in septic shock was associated with lower in-hospital mortality compared to vasopressin. The addition of hydrocortisone as the initial adjunct to norepinephrine may improve clinical outcomes in septic shock, and early initiation should be considered in patients with escalating norepinephrine requirements.