Early vasopressin initiation in septic shock shows mixed mortality outcomes across different study designsEarly Vasopressin Initiation May Help Patients with Septic Shock

OBJECTIVE: To determine the optimal timing for initiating vasopressin in septic shock. METHODS: First, we performed a retrospective analysis of a multicenter registry of adults with septic shock to evaluate associations between vasopressin initiation timing-defined by norepinephrine (NE) dose at initiation or time from first vasopressor use-and clinical outcomes. Second, we conducted a systematic review and meta-analysis integrating these registry data with randomized controlled trials (RCTs) and observational studies comparing early versus non-early vasopressin initiation. The primary outcome was mortality. RESULTS: The registry analysis included 2001 patients. Initiation of vasopressin at an NE dose ≥0.5 μg/kg/min (adjusted odds ratio [aOR] 2.15, 95% CI 1.59-2.92) and delays of 6-24 hours after initial vasopressor use (aOR 1.59, 95% CI 1.21-2.11) were associated with higher 28-day mortality compared with initiation at NE doses <0.25 μg/kg/min and within 2 hours, respectively. The meta-analysis included 15 studies (5 RCTs and 10 observational studies). In RCTs, early vasopressin initiation was not associated with reduced mortality (OR 0.84, 95% CI 0.66-1.07) but was associated with a lower requirement for renal replacement therapy (OR 0.46, 95% CI 0.26-0.81). In observational studies, early initiation was associated with lower mortality (OR 0.71, 95% CI 0.60-0.84) and shorter ICU LOS (mean difference -1.06 days, 95% CI -1.94 to -0.18). CONCLUSION: Earlier vasopressin initiation may offer clinical benefits in septic shock. However, as evidence is primarily observational and findings vary by study design, further high-quality randomized studies are warranted.