(1565) Shockingly Vague: Comparing Adjunctive Measures in Septic Shock

Introduction: Norepinephrine (NE) is widely established as the first-line agent for hemodynamic support in septic shock. The timing and order of initiation of vasopressin and hydrocortisone remains highly debated with recent literature suggesting lower mortality with early hydrocortisone initiation. The purpose of this study was to compare the effectiveness and safety of vasopressin versus hydrocortisone as adjuncts to NE in septic shock.

Methods: This was a multicenter, retrospective study conducted from February 2020 to July 2023 in adult patients with septic shock admitted to the intensive care unit (ICU). Patients were divided into two cohorts based on the adjunctive agent administered following NE initiation: vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day). Individuals who received both study drugs within six hours of each other were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital mortality, ICU length of stay (LOS), hospital LOS, resolution of shock, time to vasopressor discontinuation, initiation of renal replacement therapy (RRT), escalation of empiric antimicrobial therapy, and safety outcomes.

Results: A total of 628 patients were included: 193 patients (30.7%) received hydrocortisone and 435 patients (69.3%) received vasopressin. Significant differences in baseline SOFA score, mechanical ventilation, and NE dose at study drug initiation were noted between study groups. Thirty-day mortality was significantly lower with hydrocortisone (49.7% vs. 60.7%, P=0.01). In-hospital mortality (37.3% vs. 53.3%, P< 0.001) and initiation of RRT (17.1% vs. 31.0%, P< 0.001) were also significantly different, favoring hydrocortisone. All other secondary outcomes were similar between groups. Approximately a quarter of patients in each group required escalation of empiric antimicrobial therapy (23.0% vs. 24.9%, p=0.608). A higher incidence of hypoglycemia and hyponatremia occurred with vasopressin.

Conclusions: Administration of hydrocortisone as an adjunct to NE in septic shock was associated with lower 30-day mortality, in-hospital mortality, and RRT initiation compared to vasopressin. Differences in baseline characteristics between study groups may account for the benefit observed with hydrocortisone.