Influence of Timing and Catecholamine Requirements on Vasopressin Responsiveness in Critically ill Patients with Septic Shock.

Despite its widespread use, there is a paucity of data to guide the optimal use of arginine vasopressin (AVP) in critically ill patients with septic shock. This multicenter retrospective cohort study conducted in critically ill adults sought to evaluate the role of catecholamine requirements and timing on responsiveness to AVP. Responsiveness was defined as both a decrease in ≥ 50% of catecholamine requirements and no decrease in mean arterial pressure (MAP) at 4 hours post-AVP initiation. Primary outcomes of interest included the proportion of patients who started AVP within 4 hours after starting catecholamine therapy, as well as baseline norepinephrine (NE) equivalents (< 15, 15-39, or ≥ 40 mcg/min). Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness. There were 300 patients included in this study, with 74 patients being responders and 226 being non-responders. There was no significant difference in the number of patients who received AVP within 4 hours from catecholamine initiation between responders and non-responders (35% vs. 42%, P = 0.29). There were more patients in the non-responder group requiring ≥ 40 mcg/min of NE equivalents at AVP initiation (30% vs. 16%, P = 0.023). Stress dose steroid use was less common in responders (35% vs. 52%, P = 0.011), which was consistent with logistic regression analysis (OR 0.56, 95% 0.32-0.98, P = 0.044). Clinical outcomes between responders and non-responders were similar, apart from ICU (5.4% vs. 19.5%) and hospital (5.4% vs. 20.4%) mortality being lower in responders (P = 0.0032 and P = 0.0002, respectively). Shorter times to AVP initiation was not associated with responsiveness at 4 hours post-catecholamine initiation, although non-responders tended to require higher doses of NE equivalents at time of AVP initiation. Concomitant corticosteroids were associated with a lower likelihood of AVP responsiveness.