Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock

Coleman, Patrick J.; Nissen, Alexander P.; Kim, Daniel E; Ainsworth, Craig; McCurdy, Michael T.; Mazzeffi, Michael; Chow, Jonathan H.

doi:10.1177/1089253219877876

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…These results are statistically and clinically important because, contemporary evidence examining the use of human Ang-2 is mainly from the ATHOS-3 trial and its subsequent post-hoc analyses. 3,[9][10][11][12][13][14][15][16] Our study includes patients with a wide variety of shock states, including cardiogenic and hypovolemic shock, which were not studied in ATHOS-3.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] With the exception of case reports, small case series, and 1 multicenter study, studies occurring after ATHOS-3 that have not been derived from that study's dataset are sparse. [13][14][15][16][17] The purpose of our multicenter study was to assess the effectiveness of Ang-2 for the treatment of shock. Specifically, we sought to evaluate whether Ang-2 effectively increases MAP and decreases NEpi-equivalent dose.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…In those with an absolute or functional deficiency of angiotensin-converting enzyme, manifested by a ratio of angiotensin 1/angiotensin 2 of ≥ 1.63 or elevated renin levels, angiotensin 2 supplementation statistically significantly improved survival [112,113]. This vasopressor shows promising results in conditions, such as ARDS, influenza, pneumonia, cirrhosis, acute kidney injury requiring renal replacement therapy, respiratory failure requiring venovenous extracorporeal membrane oxygenation, post-cardiopulmonary bypass, cardiac arrest, and Covid-19-induced shock [114][115][116][117][118][119][120].…”

Section: Nanoparticlesmentioning

confidence: 97%

Novel Diagnostics and Therapeutics in Sepsis

et al. 2021

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Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation. Currently employed diagnostic tools are ill-equipped to rapidly diagnose sepsis and isolate the offending pathogen, which limits the ability to offer targeted and lowest-toxicity treatment. Cutting edge diagnostics and therapeutics in development may improve time to diagnosis and address two broad management principles: (1) source control by removing the molecular infectious stimulus of sepsis, and (2) attenuation of the pathological immune response allowing the body to heal. This review addresses novel diagnostics and therapeutics and their role in the management of sepsis.

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“…Angiotensinogen is a protein synthesized by the liver and is the precursor to angiotensin I (Ang-1). [40][41][42] During states of low renal perfusion, a biofeedback mechanism releases renin from juxtaglomerular cells in the afferent arterioles of the kidneys and converts angiotensinogen to Ang-1. Angiotensin I is then hydrolyzed into Ang-2 by angiotensin-converting enzyme (ACE) in the capillary endothelium, which is most densely concentrated in the lungs.…”

Section: Endogenous Production and Mechanism Of Actionmentioning

confidence: 99%

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

Heavner

McCurdy

Mazzeffi

et al. 2020

J Intensive Care Med

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Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles.

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Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock

Cited by 9 publications

References 48 publications

A Multicenter Observational Cohort Study of Angiotensin II in Shock

A Multicenter Observational Cohort Study of Angiotensin II in Shock

Novel Diagnostics and Therapeutics in Sepsis

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

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