(1017) Clinical Response to Third-Line Angiotensin II vs Epinephrine: A Propensity-Matched Cohort Study

Introduction: The appropriate vasopressor strategy in septic shock patients receiving multiple vasopressors is unknown. The addition of epinephrine to norepinephrine and vasopressin is a weak recommendation supported by low-quality evidence but remains common in clinical practice. Angiotensin-II (AT-II) offers a novel mechanism of action and, at our institution, has been used as a third-line vasopressor. The purpose of this study was to evaluate the efficacy and safety of third-line AT-II compared to third-line epinephrine in patients with refractory septic shock.

Methods: Included patients were > 17 years with a diagnosis of septic shock who received continuous infusion epinephrine or AT-II after first-line norepinephrine and second-line vasopressin between April 1, 2019 and July 31, 2022. Patients were grouped by third-line vasopressor received (epinephrine or AT-II) and subsequently matched 2:1 via calculation of predicted probabilities using logistic regression. The primary outcome was incidence of clinical response 24 hours after third-line vasopressor initiation. Secondary clinical and safety outcomes were compared between groups.

Results: Forty-six and 23 patients were included in the epinephrine and AT-II groups, respectively. Baseline characteristics were well-balanced between epinephrine and AT-II patients. Average norepinephrine-equivalent dose prior to third-line vasopressor initiation was 0.44 mcg/kg/min in the epinephrine group and 0.47 mcg/kg/min in the AT-II group (p = 0.41). Most patients required mechanical ventilation (89.1% vs 87.1% p = 0.79) and renal replacement therapy 58.7% vs 52.2%, p = 0.61). Angiotensin-II treated patients had higher, non-statistically difference, incidence of clinical response at hour 24 (28.3% vs 47.8%, p = 0.12). In-hospital mortality (73.9% vs 65.2%, p = 0.45), cardiac arrhythmia (26.1% vs. 26.1%, p = 0.21), and thromboembolism (2.2%, vs 4.3%, p = 0.61) were not different between groups.

Conclusions: Administration of AT-II as a third-line vasopressor in septic shock patients was not associated with significantly improved clinical response at hour 24 compared to epinephrine. While underpowered to detect meaningful differences, clinical observations, such as increased clinical response, warrant earlier consideration and further study of AT-II in septic shock.