Role of Angiotensin II as a Vasoactive Agent to Treat Distributive Shock With a Focus on Preliminary Data in...

In pediatric-aged patients, distributive (vasoplegic) shock is commonly caused by sepsis, anaphylaxis, or the humoral/immunologic response following cardiopulmonary bypass. In general, the first-line vasoactive agent for children is epinephrine or norepinephrine. In cases of fluid-refractory shock requiring escalating doses of catecholamines, adjunct therapies such as vasopressin, hydrocortisone, hydroxycobalamin-ascorbic acid, and methylene blue may be introduced. In 2017, the FDA approved a synthetic human angiotensin II (AT-II) infusion preparation for treating adult patients with refractory vasodilatory shock. The following educational review examines the role of AT-II as a vasoactive agent in the treatment of distributive shock with a focus on pediatric patients. A systematic search of the literature was performed to identify key publications regarding the therapeutic use of AT-II for the treatment of distributive shock in adult and pediatric patients. Prospective studies in adult patients demonstrate the efficacy of AT-II to treat refractory vasodilatory shock when escalating doses of conventional vasoactive agents (norepinephrine ≥ 0.2-0.3 μg/kg/min) have failed. In these scenarios, AT-II has been added as the third or fourth medication. There are limited trials evaluating AT-II as the primary agent for vasodilatory shock in adults. The majority of studies have shown an improvement in mean arterial pressure (MAP); however, there has been limited impact on long-term survival. Pediatric evidence to date has included 5 case reports and two larger retrospective case series encompassing a total of 44 patients. Although AT-II was generally effective in increasing the MAP, given the non-randomized and non-prospective nature of these studies, information regarding the impact on long-term outcomes is not available. Both adult and pediatric reports have outlined the potential utility of AT-II in treating vasodilatory shock as primarily a rescue agent when conventional vasoactive agents fail or dose requirements escalate. To date, evidence-based medicine demonstrates an increase in MAP with the ability to wean other vasoactive agents. The current studies do not appear to uniformly and clearly define a survival benefit. Future studies should focus on the potential survival impact of this novel vasoactive agent, further define dosing strategies, and more clearly outline its role as a primary agent or when other vasoactive agents fail.