Impact of Early versus Delayed Vasopressin Initiation on 28-Day Mortality in Older Adults with Septic Shock

The optimal timing for initiating adjunctive vasopressin in septic shock remains controversial, with limited evidence specific to older adults who may have altered physiological responses. This study aimed to investigate the association between the timing of vasopressin initiation and 28-day mortality in older adults with septic shock.

In this retrospective observational cohort study, we enrolled 197 older adults (≥65 years) with septic shock who received vasopressin within 72 hours of norepinephrine initiation. Patients were categorized into an early group (vasopressin within 6 hours of norepinephrine; n=119) and a delayed group (vasopressin between 6-72 hours; n=78). The primary outcome was 28-day all-cause mortality, analyzed using multivariable Cox regression adjusting for potential confounders.

The 28-day mortality was significantly lower in the early vasopressin group compared to the delayed group (36.1% vs. 57.7%, p<0.01). In the multivariate Cox analysis, early initiation was independently associated with a reduced risk of 28-day mortality (HR = 0.48, 95% CI: 0.31-0.74, p < 0.01). Secondary outcomes also favored the early group, including a higher rate of hemodynamic response (62.2% vs. 44.9%, p=0.02), more mechanical ventilation-free days (11.9 vs. 8.4 days, p=0.03) and more continuous renal replacement therapy (CRRT)-free days (13.2 vs. 9.5 days, p=0.03).

In older adults with septic shock, early initiation of vasopressin within six hours of norepinephrine commencement was independently associated with significantly lower 28-day mortality and improved hemodynamic and organ function outcomes.