2025 Southeastern Residency Conference

Title: Evaluating the Use of Angiotensin II vs. Methylene Blue in the Management of Refractory Distributive Shock in Patients with Liver Failure  
Authors: Kaanan Shah, Marion Javellana, Peter Moran, Kendall Huntt, Alley Killian  
Background: Angiotensin II (AGII) and methylene blue (MB) are agents used in the management of refractory shock as adjunctive agents, typically in combination with catecholamines, vasopressin, and/or corticosteroids. However, many studies have excluded patients with liver failure. In liver failure, patients experience a high cardiac output and low systemic vascular resistance causing hypotension. These agents are thought to be beneficial in this setting as AGII activates angiotensin type 1 receptors thus increasing blood pressure and systemic vascular resistance and MB disrupts the cGMP signaling pathway leading to vasoconstriction. The purpose of this study is to compare the efficacy of AGII and MB in refractory shock in patients with liver failure.  
Methods: The institutional review board approved this single center, retrospective chart review study. Patients over the age of 18 that received AGII for at least 3 hours or a bolus dose of at least 1 mg/kg and/or a continuous infusion of MB between October 1, 2022 through September 16, 2024 were included. Patients were excluded if they had no documented liver failure, were pregnant, had active internal bleeding or cardiogenic shock, received intraoperative administration of the study agents or MB as an antidote. The primary outcome is the improvement of shock defined as a percent decrease in catecholamine and vasopressin requirement 3 hours after administration of the study agent based on norepinephrine equivalence. Secondary outcomes include percent decrease in catecholamine and vasopressin requirements at the 1-, 8-, and 24-hour marks post-initiation of the study agents, liberation from vasopressors, adverse events, length of ICU stay, and incidence of ICU mortality. Data from the primary and secondary outcomes were analyzed using intention-to-treat and continuous data was compared using the student t-test or Mann-Whitney U test to determine statistical significance.   
Results: Twenty-four patients were included, with five patients in the AGII group and 19 patients in the MB group. Vasopressor requirements decreased at the 3-hour mark after MB but increased after AGII, though not a statistically significant difference (-11.7 vs. +11.3; p = 0.783). Only 18 patients in the MB group and 4 patients in the AGII group survived to the 8-hour mark and there was an increase in NE equivalence with both MB and AGII (+ 9.9 vs. + 38.3; p = 0.731). Additionally, only 15 patients in the MB group and 3 patients in the AGII group survived to the 24-hour mark and patients in the MB group saw a decrease in NE equivalence while patients in the AGII group saw an increase (-15.1 vs. +71.8; p = 0.331). Mortality in the 94.7% in the MB group and 80% in the AGII group. One patient in each group was successfully liberated from vasopressors.     
Conclusions: AGII and MB are agents used to treat refractory shock. This study demonstrated MB’s potential benefit, compared to AGII, in managing shock in patients with liver failure with an initial reduction in vasopressor requirements. The lack of sustained response to the study agents could potentially be explained by the severity of hepatic dysfunction and associated vasodilatory shock. The two patients who were liberated from vasopressors received liver transplants. Limitations of this study include a small and unequal patient population, the retrospective, single-center nature of the study, and its local applicability. This highlights a need for further research on these agents in the management of shock in patients with liver failure in order to find a beneficial place in therapy for them.