Angiotensin II and Vasopressin for Vasodilatory Shock: A Critical Appraisal of Catecholamine-Sparing Strategies

Heavner, Mojdeh; McCurdy, Michael T.; Mazzeffi, Michael; Galvagno, Samuel M.; Tanaka, Kenichi A.; Chow, Jonathan H.

doi:10.1177/0885066620911601

Cited by 9 publications

(6 citation statements)

References 85 publications

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“…20,23 The catecholamine-sparing effects of non-catecholamine vasopressors may have benefit in reducing mortality and adverse effects associated with high-dose catecholamines. 24,25 This relationship, however, is highly impacted by severity of illness, and the direct impact of catecholamine-sparing agents on mortality from shock is unclear. Future prospective research should further evaluate the relationship between Ang-2, catecholamine requirements, and clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Observational Cohort Study of Angiotensin II in Shock

Smith

Newsome

Guo

et al. 2020

J Intensive Care Med

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Introduction: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. Methods: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. Results: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. Conclusion: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.

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Section: Discussionmentioning

confidence: 99%

A Multicenter Observational Cohort Study of Angiotensin II in Shock

Smith

Newsome

Guo

et al. 2020

J Intensive Care Med

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“…Excess levels of circulating angiotensin 1-7, together with excess bradykinin, which increases vascular permeability, are associated with increased hypotension. 23 Consistent with this hypothesis, prolonged CPB duration is an independent risk factor for the occurrence of vasoplegia. 24 In addition, an inflammatory response has been reported when blood comes into contact with the CPB circuitry that, together with inflammation occurring within the pulmonary endothelium upon reperfusion of the lungs when the patient is taken off CPB, 25 would be presumed to diminish ACE activity and exacerbate the relative deficit of angiotensin II.…”

Section: Discussionmentioning

confidence: 71%

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

Klijian

Khanna

Reddy³

et al. 2021

Journal of Cardiothoracic and Vascular Anesthesia

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Objective: The present study investigated outcomes in patients with vasoplegia after cardiac surgery treated with angiotensin II plus standard-ofcare 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. Setting: Multicenter, multinational study. Participants: Sixteen patients with vasoplegia after cardiac surgery with cardiopulmonary bypass were enrolled. Interventions: Angiotensin II plus standard-of-care vasopressors (n = 9) compared with placebo plus standard-of-care vasopressors (n = 7). Measurements and Main Results: The primary endpoint was mean arterial pressure response (mean arterial pressure 75 mmHg or an increase from baseline of 10 mmHg at hour 3 without an increase in the dose of standard-of-care vasopressors). Vasopressor sparing and safety also were assessed. Mean arterial pressure response was achieved in 8 (88.9%) patients in the angiotensin II group compared with 0 (0%) patients in the placebo group (p = 0.0021). At hour 12, the median standard-of-care vasopressor dose had decreased from baseline by 76.5% in the angiotensin II group compared with an increase of 7.8% in the placebo group (p = 0.0013). No venous or arterial thrombotic events were reported.

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Section: Discussionmentioning

confidence: 99%

“…38 This reaction will directly trigger the sympathetic nervous system while also triggering the release of calcium (Ca2+) from the sarcoplasmic reticulum of smooth muscle cells, causing vasoconstriction. 39 This interaction prompts the hemodynamic to improve which can then reduce the mortality rate in shock patients. This is in line with the results of the study by Wieruszewski et al which states that the level of hemodynamic responsiveness of patients has a significant effect on the 30-day mortality rate of patients in shock.…”

Section: Discussionmentioning

confidence: 99%

“… 42 Administration of non-catecholamine vasopressors in the treatment of refractory shock can reduce catecholamine doses and can reduce the potential of toxicity associated with high-dose catecholamine therapy through vasoconstriction with different mechanisms. 39 Chawla et al showed that the number of catecholamine use in patients who had been given Ang-2 was lower than those who received placebo. 7 Using a sparing effect on a vasopressor patient will reduce the patient’s morbidity and length of stay (LOS).…”

Section: Discussionmentioning

confidence: 99%

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How Effective is Angiotensin II in Decreasing Mortality of Vasodilatory Shock? A Systematic Review

Semedi

Rehatta

Soetjipto

et al. 2023

OAEM

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Background: Patients with severe vasodilation accompanied by refractory hypotension despite high doses of vasopressors were associated with a high mortality rate. The Ang-2 for the Treatment of High-Output Shock (ATHOS) 3 trial demonstrated that angiotensin 2 (Ang-2) could effectively increase MAP and blood pressure in vasodilatory shock patients. This systematic review aims to summarize the impact of Ang-2 for the treatment of vasodilatory shock on clinical outcomes, including length of stay, MAP level (before and after), and mortality also Ang-2 dose needed. Methods: A systematic search in PubMed, Sage, ScienceDirect, Scopus and Gray literature was conducted to obtain studies about the use of Ang-2 in vasodilatory shock patients. Results: In all of the studies that we obtained, there were different results regarding mortality in patients with vasodilatory shock with Ang-2. Mortality was significantly lower when Ang-2 was administered to patients with elevated renin. The initial dose of Ang-2 can be started at 10-20 ng/kg/min, but there is no agreement on the maximum dose. Ang-2 may be considered a third-line vasopressor if the targeted MAP has not been achieved after administration of norepinephrine >200 ng/kg/min for more than 6 hours. Although not statistically significant, the use of Ang-2 can reduce the length of stay in the ICU and in the hospital when compared to patients without Ang-2 therapy, in addition to reducing the dose of vasopressor. Conclusion: Overall, the use of Ang-2 has potential to be a regimen for patients with vasodilatory shock. Further study is needed to obtain more data.

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Angiotensin II and Vasopressin for Vasodilatory Shock: A Critical Appraisal of Catecholamine-Sparing Strategies

Cited by 9 publications

References 85 publications

A Multicenter Observational Cohort Study of Angiotensin II in Shock

A Multicenter Observational Cohort Study of Angiotensin II in Shock

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

How Effective is Angiotensin II in Decreasing Mortality of Vasodilatory Shock? A Systematic Review

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