Weaning Approaches for Vasopressin in Sepsis - a Randomized Controlled Trial of Titrated Versus Abrupt Discontinuation During Stabilization of Septic Shock - WAVES Trial

Catecholamine infusions are usually tapered gradually in a titrated manner. However, little is known about how to manage adjunctive therapies such as vasopressin. While catecholamines have a short half-life (2-3 minutes), vasopressin's half-life ranges from 10 to 20 minutes. Although endogenous vasopressin levels are depleted in the early phase of shock, they are restored during recovery. Given its pharmacokinetic profile and the endogenous dynamics across different phases of shock, the optimal approach to vasopressin withdrawal - whether titrated or abrupt - remains unclear.

In 2021, a study was published comparing abrupt versus gradual vasopressin discontinuation. This was a retrospective observational study including 1,318 patients. Using ICU length of stay as the primary outcome, no significant difference was observed between groups (abrupt discontinuation: 7.9 days; gradual discontinuation: 7.3 days; p = 0.6). Similarly, there was no difference in the incidence of clinically significant hypotension (abrupt: 39.7%; gradual: 41.7%; p = 0.53). However, when stratifying patients based on whether catecholamine infusions were still ongoing at the time of vasopressin discontinuation, the results reversed in terms of ICU stay (abrupt: 9.2 days; gradual: 7.6 days), although this difference was not statistically significant (p = 0.24). In 2023, another retrospective observational study was published comparing abrupt versus gradual vasopressin withdrawal, including 74 patients. No difference was found in the incidence of clinically significant hypotension (abrupt: 57.1%; gradual: 52.3%; p = 0.68), nor in ICU length of stay. It is important to note, however, that in this cohort only patients who had already discontinued catecholamines prior to vasopressin withdrawal were included.