How Can We Define a Place in Therapy for Angiotensin II After Cardiac Surgery?

Abstract

In a recent study by Klijian et al. that evaluated angiotensin II in cardiac surgery patients with postoperative vasoplegia, the drug was associated with a significant increase in mean arterial pressure (MAP) compared with placebo.1Klijian A. Khanna A.K. Reddy V.S. et al.Treatment with angiotensin II is associated with rapid blood pressure response and vasopressor sparing in patients with vasoplegia after cardiac surgery: A post-hoc analysis of angiotensin II for the treatment of high-output shock (ATHOS-3) study.J Cardiothorac Vasc Anesth. 2020; Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar Even though these results appear promising for a condition associated with substantial increases in morbidity and mortality, several factors should be considered. The post-hoc analysis of ATHOS-3 described patients initiated on angiotensin II (n = 9) compared with placebo (n = 7). Even though patients were receiving similar norepinephrine-equivalent doses at baseline, severity of illness remained unclear because 93.8% of patients were reported to have an APACHE II score ≤30. The use of vasopressin in the study population was surprisingly low considering that vasopressin generally is accepted as a first-line agent for catecholamine-resistant hypotension attributable to postoperative vasoplegia (angiotensin II 66.7%, placebo 57.1%). Even though vasopressin is Food and Drug Administration–approved for doses up to 0.1 U/min for postcardiotomy shock, only one patient in the placebo group achieved this dose.2Par Pharmaceutical Companies, IncVasostrict [package insert]. Par Pharmaceutical Companies, Inc, Spring Valley, NY2014Google Scholar The VANCS trial, which evaluated 300 patients with postoperative vasoplegia after cardiac surgery, demonstrated that initial treatment with vasopressin was associated with a reduced incidence of mortality or severe complications compared with norepinephrine.3Hajjar L.A. Vincent J.L. Galas F.R. et al.Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: The VANCS randomized controlled trial.Anesthesiology. 2017; 126: 85Crossref PubMed Scopus (162) Google Scholar Methylene blue and hydroxocobalamin are adjunctive therapies that interfere with nitric oxide metabolism, a key contributor to endothelial relaxation in refractory vasodilatory shock. Methylene blue has a long history of off-label use for the management of postoperative vasoplegia, with a reduction in vasopressor requirements of at least 20% expected in approximately 40% of patients.4Mazzeffi M. Hammer B. Chen E. et al.Methylene blue for postcardiopulmonary bypass vasoplegic syndrome.Ann Card Anaesth. 2017; 20: 178Crossref PubMed Scopus (27) Google Scholar Hydroxocobalamin is an emerging therapy that has demonstrated 73% improvement in MAP and decreased vasopressor requirements in patients with postoperative vasoplegia.5Shah P. Reynolds P.S. Pal N. et al.Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: A case series.Can J Anesth. 2018; 65: 560Crossref PubMed Scopus (40) Google Scholar It is unclear whether patients in the post-hoc analysis of ATHOS-3 received any of these common adjunctive therapies and, if so, the subsequent effect of these drugs on MAP and vasopressor requirements. Because early administration of methylene blue has been shown to improve survival, it also would be interesting to know the timing of angiotensin II initiation in the ATHOS-3 subpopulation.6Mehaffey J.H. Johnston L.E. Hawkins R.B. et al.Methylene blue for vasoplegia syndrome after cardiac operation: Early administration improves survival.Ann Thorac Surg. 2017; 104: 36-41Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Angiotensin II may be a promising option for the management of postoperative vasoplegia. Considering the high drug acquisition cost and lack of data on clinical outcomes, additional information is needed to better determine how to implement this therapy in a cardiac surgery population. Treatment With Angiotensin II Is Associated With Rapid Blood Pressure Response and Vasopressor Sparing in Patients With Vasoplegia After Cardiac Surgery: A Post-Hoc Analysis of Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) StudyJournal of Cardiothoracic and Vascular AnesthesiaVol. 35Issue 1PreviewObjective: The present study investigated outcomes in patients with vasoplegia after cardiac surgery treated with angiotensin II plus standard-of-care vasopressors. Vasoplegia is a common complication in cardiac surgery with cardiopulmonary bypass and is associated with significant morbidity and mortality. Approximately 250,000 cardiac surgeries with cardiopulmonary bypass are performed in the United States annually, with vasoplegia occurring in 20%to-27% of patients.Design: Post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Full-Text PDF Open Access