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

Abstract

Introduction: 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. Methods: 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. Results: 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). Conclusion: 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.

Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock

“…However, of note, several factors were found to significantly affect vasopressin responsiveness in the study including catecholamine dose at vasopressin initiation, stress dose steroid use, and total duration of vasopressor therapy, among others. 11 Consequently, the possibility of confounding factors affecting vasopressin responsiveness related to time from catecholamine initiation to vasopressin addition cannot be overlooked, especially in the context of a retrospective analysis. A recently published study by Sacha and colleagues evaluated how catecholamine dose at vasopressin initiation affects clinical outcomes in patients with septic shock.…”

Vasopressin Initiation as a Second-Line VasoPressor in Early Septic Shock (VISPSS)

“…Therefore, there may have been more vasopressin responders included in the study by Sacha et al highlighting the mortality benefit. 14 While noting variability in outcomes, it is important to observe the differences in patient populations when comparing our study findings to those of Sacha et al and Jakowenko et al 14,20 Although Jakowenko et al assessed patients with septic shock, the overall patient population seemed to be less ill in comparison to the patient population described in this study. In general, the patients who met criteria for septic shock presented with less baseline comorbidities (hypertension, atrial fibrillation, and ESRD) in addition to lower SOFA scores (median ranging from 9-10 between groups) and lower rates of mechanical ventilation (ranging from 53%-65% between groups).…”

“…While noting variability in outcomes, it is important to observe the differences in patient populations when comparing our study findings to those of Sacha et al and Jakowenko et al 14,20…”

“…15,19 A recent study by Jakowenko et al assessed the timing of vasopressin initiation in patients with septic shock. 20 At baseline, patients were median of 64 years of age, SOFA scores ranging from 9 to 10, and median lactate was < 3 mmol/L. Both ICU and hospital mortality were lower in responders compared to non-responders (p < 0.05).…”

“…Moreover, vasopressor duration was also significantly lower in the responders versus non-responders (p < 0.05). 20 Figure 1. Kaplan-Meier Curve on time to vasopressor discontinuation.…”