Vasopressin and its analogues in patients with septic shock: holy Grail or unfulfilled promise?

Critical Care volume 29, Article number: 333, Published: 29 July 2025

Abstract

The Surviving Sepsis Campaign (SSC) recommends norepinephrine as first-line vasopressor in patients with septic shock. For many years, there has been growing evidence that high doses of norepinephrine might have cardiac and immunological adverse effects and be associated with poorer outcomes. Current SSC guidelines therefore suggest adding vasopressin, a non-catecholaminergic vasopressor, as a second-line vasopressor rather than increasing the norepinephrine dose in patients requiring doses of norepinephrine base > 0.25–0.50 µg/kg/min, after excluding persistent hypovolemia and cardiac dysfunction. Vasopressin is a peptide hormone that causes vasoconstriction through its specific receptor, the arginine vasopressin receptor V1. Up to one-third of patients with septic shock may have vasopressin deficiency, which contributes to refractory septic shock. Vasopressin use is associated with a norepinephrine-sparing effect, which may in turn reduce the complications induced by high-doses of norepinephrine, by decreasing the vasopressor load: this is the concept of decatecholaminization. Nevertheless, the use of vasopressin in patients with septic shock has not yet demonstrated clear benefits in terms of patient outcomes, such as less cardiotoxicity, reduced use of renal replacement therapy or decreased mortality. The heterogeneity in the use of vasopressin and the definition of early vasopressin administration between different studies as well as many unresolved issues regarding the use of vasopressin in patients with septic shock could explain the absence of clear and relevant clinical benefits. Thus, the identification of subgroups of patients likely to benefit the most from vasopressin, the management of vasopressin administration (time to initiation, optimal doses, weaning strategy) and a better understanding of the interactions between vasopressin and corticosteroids represent major areas of research for future studies.