Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (VASST)

Vasopressin is released endogenously in septic shock but levels fall over time. Exogenous vasopressin at low doses (0.03 units/min) acts as a vasopressor without direct cardiac effects, potentially allowing norepinephrine dose reduction.

Multicenter RCT (27 centers, n=778) comparing vasopressin 0.01–0.03 units/min vs. norepinephrine 5–15 mcg/min in septic shock patients already on norepinephrine.

No significant difference in 28-day mortality (35.4% vasopressin vs 39.3% norepinephrine, p=0.26). In a pre-specified subgroup with less severe shock (norepinephrine <15 mcg/min), vasopressin reduced mortality (26.5% vs 35.7%, p=0.05).

Vasopressin 0.03 units/min can be added to norepinephrine as a second-line vasopressor in septic shock to reduce norepinephrine requirements. It is not superior to norepinephrine as monotherapy. Per SSC guidelines, add vasopressin when norepinephrine dose is ≥0.25 mcg/kg/min.

Open-label. Subgroup analysis (less severe shock) was hypothesis-generating only. Fixed dose of vasopressin used.