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High-dose vitamin B 12 is a potential treatment for patients with vasodilatory shock that is refractory to other therapies. Vasodilatory shock is characterized by low blood pressure and low systemic vascular resistance. Nitric oxide and hydrogen sulfide, two potential targets of high-dose vitamin B 12 given as hydroxocobalamin, facilitate this syndrome. This review explores the relationship between high-dose vitamin B 12 and hemodynamic outcomes in adults with vasodilatory shock and provides an update on the literature since a 2019 review on this topic. A literature search of studies published in the past 5 years was conducted in the CINAHL, PubMed, Cochrane, and EMBASE databases in May 2023. After assessing for eligibility, eight studies met this review's inclusion criteria. Seven of the eight studies reported decreased vasopressor requirements for part or all of the study samples after receiving a hydroxocobalamin infusion. However, not all patients responded to hydroxocobalamin. These findings are limited by patient selection and differences in the timing of vasopressor requirement and blood pressure outcome assessments. The current evidence is promising as to whether vitamin B 12 , given as a hydroxocobalamin infusion, may improve hemodynamic outcomes in vasodilatory shock, but the evidence is of low quality. The use of hydroxocobalamin to treat refractory, vasodilatory shock remains investigative. Larger randomized controlled trials are required to elucidate the role of vitamin B 12 in treating refractory, vasodilatory shock, including in conjunction with other alternative therapies such as methylene blue and corticosteroids., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Purpose: Angiotensin II is approved for catecholamine-refractory vasodilatory shock but the conversion dose ratio from norepinephrine to angiotensin II remains unclear., Methods: We conducted a post-hoc analysis of the Acute Renal effects of Angiotensin II Management in Shock (ARAMIS) trial involving patients with vasodilatory hypotension. We determined the norepinephrine equivalent dose immediately prior to angiotensin II initiation and calculated the conversion dose ratio between norepinephrine and angiotensin II. We performed subgroup analyses based on recent exposure to angiotensin receptor blockers (ARBs) and renin levels at baseline., Results: In 37 patients, the median conversion dose ratio between norepinephrine equivalent and angiotensin II was to 10:1 for norepinephrine bitartrate (5:1 for norepinephrine base). The conversion ratio was not affected by the baseline renin, with a median ratio of 10 (7-21) in the high renin group versus 12 (5-22) in the low renin group. Finally, exposure to ARBs prior admission appeared to diminish the conversion ratio with a median ratio of 7 (4-13) in ARB patients vs. 12 (7-22) in non-ARB patients., Conclusions: The norepinephrine to angiotensin II conversion dose ratio is 10:1 in a vasodilatory hypotension population. These findings can guide clinicians and researchers in the use, dosing, and study of angiotensin II in critical care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rinaldo Bellomo reports equipment, drugs, or supplies was provided by La Jolla Pharmaceutical Company. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Vasoplegic shock after cardiac surgery is characterized by hypotension, a high cardiac output, and vasodilation. Much of the understanding of this pathologic state is informed by the understanding of septic shock. Adverse outcomes and mortality are increased with vasoplegic shock. Early recognition and a systematic approach to its management are critical. The need for vasopressors to sustain an adequate blood pressure as well as pharmacologic adjuncts to mitigate the inflammatory inciting process are necessary. The rationale behind vasopressor escalation and consideration of adjuncts are discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P  < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P  < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min ( P  = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P  = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P  = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Introduction: Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure., Areas Covered: VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP., Expert Opinion: Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.

Background: Refractory vasodilatory shock is a state of uncontrolled vasodilation associated with underlying inflammation and endothelial dysregulation. Rescue therapy for vasoplegia refractory to catecholamines includes methylene blue (MB) which restores vascular tone. We hypothesized that (1) at least 40% of critically ill patients would respond positively to MB administration and (2) that those who responded to MB would have a survival benefit., Methods: This study was a retrospective review that included all adult patients admitted to an intensive care unit treated with MB for the indication of refractory vasodilatory shock. Responders to MB were identified as those with a ≥ 10% increase in mean arterial pressure (MAP) within the first 1-2 hours after administration. We examined the association of mortality to the groups of responders versus non-responders to MB. A subgroup analysis in patients undergoing continuous renal replacement therapy (CRRT) was also performed. Statistical calculations were performed in Microsoft Excel® (Redmond, WA, USA). Where appropriate, the comparison of averages and standard deviations of demographics, dosing, MAP, and reductions in vasopressor dosing were performed via Chi squared, Fisher's exact test, or two-tailed t-test with a p-value < 0.05 being considered as statistically significant. After using the F-test to assess for differences in variance, the proper two tailed t-test was used to compare SOFA scores among responders versus non-responders., Results: A total of 223 patients were included in the responder analysis; 88 (39.5%) had a ≥ 10% increase in MAP post-MB administration that was not associated with a significant change in norepinephrine requirements between responders versus non-responders (p=0.41). There was a non-statistically significant trend (21.6% vs 14.8%, p=0.19) toward improved survival to hospital discharge in the MB responder group compared to the non-responder group. In 70 patients undergoing CRRT, there were 33 responders who were more likely to survive than those who were not (p = 0.0111)., Conclusions: In patients with refractory shock receiving MB, there is a non-statistically significant trend toward improved outcomes in responders based on a MAP increase >10%. Patients supported with CRRT who were identified as responders had decreased ICU mortality compared to non-responders., (© 2022. The Author(s).)

Purpose: The aim of this study was to analyse the course of adrenomedullin (ADM) and endothelin-1 (ET-1) levels in patients with vasodilatory shock after cardiac surgery and to explore differences compared to patients after uncomplicated coronary artery bypass graft (CABG) surgery. ADM and ET-1 are involved in the vasomotor response during vasodilatory shock., Materials and Methods: We included 32 patients with vasodilatory shock (study group) and 10 patients after uncomplicated CABG surgery (control group). Daily measurements of MR-proADM and CT-proET-1 (stable surrogate markers for ADM and ET-1) were collected during the first 7 postoperative days., Results: MR-proADM and CT-proET-1 levels were significantly elevated in the study group when compared to the control group. In addition, the course of both biomarkers was significantly different in the study versus control group. Higher levels of both biomarkers were associated with organ dysfunction (higher maximum multiple organ dysfunction score, acute kidney injury)., Conclusions: Significantly higher levels of MR-proADM and CT-proET-1 and a different course of both biomarkers were observed in patients with vasodilatory shock after cardiac surgery and seemed to be associated with organ dysfunction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients., Research Question: What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response?, Study Design and Methods: We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation., Results: Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 μg/kg/min vs +0.04 μg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients., Interpretation: In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Shock is an acute condition of circulatory failure resulting in life-threatening organ dysfunction, high morbidity and high mortality. Current management includes fluid and catecholamine therapy to maintain adequate mean arterial pressure and organ perfusion. Norepinephrine is recommended as first-line vasopressor, but other agents are available. Angiotensin II is an alternative potent vasoconstrictor without chronotropic or inotropic properties. Several studies, including a large randomized controlled trial have demonstrated its ability to increase blood pressure with catecholamine-sparing effects. Angiotensin II was consequently approved by the US FDA in 2017 and the EU in 2019 as an add-on vasopressor in vasodilatory shock. This review aims to discuss its basic pharmacology, clinical efficacy, safety and future perspectives.

Study Objective: Vasodilatory shock is the most common type of shock. Catecholamine vasopressors are the cornerstone of hemodynamic therapy but carry risks. Angiotensin II (AT 2 ) was recently approved, and other novel agents (selepressin and terlipressin) are under investigation and used outside the United States (terlipressin). We performed a systematic review to summarize the efficacy and safety of these novel vasopressors and to offer guidance on their appropriate use., Design: Systematic review of controlled trials., Methods: Numerous databases were searched using terms related to angiotensin II, selepressin, terlipressin, vasopressor , and shock . Twenty-one citations, including 16 prospective comparative trials and 5 post hoc analyses reporting effects of AT 2 , selepressin, and terlipressin, were reviewed for data on outcomes related to hemodynamic measures, mortality, severity and duration of illness, concomitant vasopressor utilization, and adverse effects. Findings from eligible literature are described qualitatively using Cochrane methods., Results: Fourteen controlled trials were assessed after exclusion of 2 dated trials of a distinct AT 2 formulation. Trials are limited for AT 2 (n = 2) and selepressin (n = 1), while terlipressin was investigated in 11 small trials. Overall, the trials have an unclear risk of bias. Most report mean arterial pressure (MAP) as primary end point, and all indicate novel vasopressors increase MAP compared to placebo and to a similar degree as with catecholamine vasopressors. Mortality findings are preliminary, as they have been limited to specific subgroups in trials of terlipressin and post hoc analyses of one trial of AT 2 . Trials reported safety concerns for each agent including thromboembolism with AT 2 and ischemia with terlipressin/selepressin., Conclusion: In this systematic review, controlled trials of novel vasopressors in treatment of vasodilatory shock were limited and of low quality. Angiotensin II, selepressin, and terlipressin appear to significantly increase MAP, but further study is required, particularly for selepressin, to determine their safety, efficacy, and role in treatment of vasodilatory shock.

Background: In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study., Methods: We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes., Results: Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30-676.00 pg/mL] vs 42 pg/mL [IQR 30.46-87.34 pg/mL] in controls; P <  0.0001) and median ANG I/II ratio (1.63 [IQR 0.98-5.25] vs 0.4 [IQR 0.28-0.64] in controls; P <  0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85-299.50 pg/mL] vs 97 pg/mL [IQR 35.27-181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P <  0.0001), lower ANG II levels (P <  0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P <  0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36-0.88; P = 0.01) on unadjusted analyses., Conclusions: Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction., Trial Registration: ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.

The Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) trial demonstrated the vasopressor effects and catecholamine-sparing properties of angiotensin II. As a result, the Food and Drug Administration has approved angiotensin II for the treatment of vasodilatory shock. This review details the goals of treatment of vasodilatory shock in addition to the history, current use, and recent research regarding the use of angiotensin II. An illustrative case of the use of angiotensin II is also incorporated for understanding the clinical utility of the drug., (Copyright © 2018 Elsevier Inc. All rights reserved.)

With more than 2000 ventricular assist devices (VAD) placed annually in the United States, understanding postoperative management is important. One of the most common postoperative morbidities encountered with VAD implantation is vasodilatory shock. The mechanisms for this phenomenon are numerous and include cellular and hormonal aberrancies unique to the VAD recipient. Management of vasodilatory shock in VAD patients needs to be undertaken with an understanding of the side effects associated with each treatment, especially the effects on the right ventricle and pulmonary vasculature. This article focuses on the incidence, the pathogenesis, the consequences, and the management of vasodilatory shock in the postoperative VAD patient., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Vasodilatory shock is a critical manifestation of cardiovascular failure. There is uncontrolled vasodilation and vascular hyporesponsiveness to endogenous vasoconstrictors, causing the failure of physiologic vasoregulatory mechanisms. Unfortunately, only few randomized studies exist to guide clinical management and hemodynamic stabilization in patients who do not respond to the standard approach of managing vasodilatory shock. The present review offers the latest updates in management of this important clinical entity and a guidance framework for future research. [ABSTRACT FROM AUTHOR]

Abstract: Classification of shock according to the situation in which it presents is helpful in developing a diagnostic strategy. Some causes of shock are immediately apparent; others are less so. Diagnosis is part of a process of advanced first aid in which simultaneous assessment, resuscitation, monitoring and risk assessment should take place. Investigations should be targeted towards the clinical situation in which they take place. [ABSTRACT FROM AUTHOR]