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      Angiotensin-II for vasoplegia following cardiac surgery

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          Abstract

          Introduction

          The objective of this study was to describe the implementation and outcomes of a protocol outlining angiotensin-II utilization for vasoplegia following cardiac surgery.

          Methods

          This was a retrospective chart review at a single-center university hospital. Included patients received angiotensin-II for vasoplegia refractory to standard interventions, including norepinephrine 20 mcg/min and vasopressin 0.04 units/min, following cardiac surgery between April 2021 and April 2022.

          Results

          30 patients received angiotensin-II for refractory vasoplegia. Adjunctive agents at angiotensin-II initiation included corticosteroids (26 patients; 87%), epinephrine (26 patients; 87%), dobutamine (17 patients; 57%), dopamine (9 patients; 30%), milrinone (2 patients; 7%), and hydroxocobalamin (4 patients; 13%). At 3 hours, the median mean arterial pressure increased from baseline (70 vs 61.5 mmHg, p = .0006). Median norepinephrine doses at angiotensin-II initiation, 1 hour, 3 hours, and angiotensin-II discontinuation were 0.22, 0.16 ( p = .0023), 0.10 ( p < .0001), and 0.07 ( p < .0001) mcg/kg/min. Median dobutamine doses decreased throughout angiotensin-II infusion from eight to six mcg/kg/min ( p = .0313). Other vasoactive medication doses were unchanged. Three patients (10%) subsequently received hydroxocobalamin. Thirteen (43.3%) and five (16.7%) patients experienced mortality by day 28 and venous or arterial thrombosis events, respectively.

          Conclusions

          The administration of angiotensin-II to vasoplegic patients following cardiac surgery was associated with increased mean arterial pressure, reduced norepinephrine dosages, and reduced dobutamine dosages.

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          Most cited references36

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          Angiotensin II for the Treatment of Vasodilatory Shock.

          Background Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. Methods We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. Results A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12). Conclusions Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).
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            Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery.

            The discovery of nitric oxide as mediator in cardiac postoperative vasoplegia encourages the use of inhibitory drugs such as methylene blue. This drug has been used with favorable results in isolated cases. The purpose of this article is to analyze the incidence of the postoperative vasoplegic syndrome, to consider its prognosis, and to evaluate the effect of intravenous methylene blue on mortality. Cardiac surgery patients were consecutively included. Vasoplegic syndrome was defined by the presence of the following five criteria: (1) hypotension, (2) low filling pressures, (3) high or normal cardiac index, (4) low peripheral resistance, and (5) vasopressor requirements. Those with vasoplegia were randomized to receive 1.5 mg/Kg of methylene blue or a placebo. A p value less than 0.05 was considered significant. Six hundred thirty eight cardiac surgery patients were consecutively included in this study. Fifty-six of these patients fulfilled vasoplegia criteria (8.8%) resulting in higher mortality (10.7% or 6 of 56 patients vs 3.6% or 21 of 582 patients; p value = 0.02). Those treated with methylene blue showed morbidity and mortality reductions (0% versus 21.4% or 6 of 28 patients; p value = 0.01). The duration of the vasoplegic syndrome was shorter in those patients treated with the drug, lasting less than 6 hours in all patients. Patients in the control group showed a slower recovery, lasting more than 48 hours in 8 patients (p value = 0.0007). Vasoplegic postoperative syndrome was seen in 8.8% of all patients. Outcome in patients with vasoplegia was worse with increased morbidity and mortality. The use of methylene blue reduced the high mortality in this population.
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              Vasoplegic syndrome following cardiothoracic surgery—review of pathophysiology and update of treatment options

              Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Perfusion
                Perfusion
                SAGE Publications
                0267-6591
                1477-111X
                November 13 2023
                Affiliations
                [1 ]Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN, USA
                [2 ]Department of Anesthesia, Division of Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
                Article
                10.1177/02676591231215920
                8cd6ecbb-709a-4b45-9c25-be67f1469b32
                © 2023

                https://creativecommons.org/licenses/by-nc/4.0/

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