Purpose Vasoplegia is a common complication after cardiac surgery and is related to the use of cardiopulmonary bypass (CPB). Despite its association with increased morbidity and mortality, no consensus exists in terms of its treatment. In December 2017, angiotensin II (AII) was approved by the Food and Drug Administration (FDA) for use in vasodilatory shock; however, except for the ATHOS-3 trial, its use in vasoplegic patients that underwent cardiac surgery on CPB has mainly been reported in case reports. Thus, the aim of this review is to collect all the clinically relevant data and describe the pharmacologic mechanism, efficacy, and safety of this novel pharmacologic agent for the treatment of refractory vasoplegia in this population. Methods Two independent reviewers performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library using relevant MeSH terms (Angiotensin II, Vasoplegia, Cardiopulmonary Bypass, Cardiac Surgical Procedures). Results The literature search yielded 820 unique articles. In total, 9 studies were included. Of those, 2 were randomized clinical trials (RCTs) and 6 were case reports and 1 was a retrospective cohort study. Conclusions AII appears to be a promising means of treatment for patients with post-operative vasoplegia. It is demonstrated to be effective in raising blood pressure, while no major adverse events have been reported. It remains uncertain whether this agent will be broadly available and whether it will be more advantageous in the clinical management of vasoplegia compared to other available vasopressors. For that reason, we should contain our eagerness and enthusiasm regarding its use until supplementary knowledge becomes available.

As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are expressed in human and animal hearts and blood vessels in a tissue-dependent manner. We summarize the changes observed in HF regarding the density, signaling and responses of α1-ARs. Conflicting findings arise from different studies concerning the influence that HF has on α1-AR expression and function; in contrast to β-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular α1-ARs. Whether α1-ARs are a therapeutic target in HF remains a matter of debate.

Introduction: Vasoplegia is a severe complication after cardiac surgery and is associated with impaired clinical outcome. Pre-operative heart failure (HF) is considered an independent predictor of post-operative vasoplegia. We hypothesize that HF patients are more susceptible to vasoplegia due to altered vascular responsiveness. In this study, vasoresponsiveness in patients undergoing cardiac surgery for HF is investigated. Methods: A prospective, observational study was conducted at Leiden University Medical Center. We included patients with HF (N=18) and without HF (N=18) who underwent cardiac surgery on cardiopulmonary bypass. Vasoresponsiveness was assessed at 4 different timepoints: 1) before induction, 2) after induction, 3) after cessation of cardiopulmonary bypass and 4) on the first postoperative day. The vascular response was recorded as change in systemic vascular resistance (SVR) after the administration of phenylephrine (bolus 2 μg/kg). Results: Thirty-six patients were included [67 (61-71) years, 78% male]. Vascular responsiveness was significantly attenuated in patients with HF compared to controls. The response to phenylephrine was already diminished at baseline in HF patients and was almost abolished after cessation of cardiopulmonary bypass (Figure). Roughly the same pattern of vasoresponsiveness was found when excluding patients that received norepinephrine. Moreover, HF patients required a significantly higher amount of noradrenaline [169.80 (IQR 14.77-318.97) ug/kg] compared to controls [3.61 (IQR 0-41.60) ug/kg] to maintain similar SVR during the first 24h postoperatively. Conclusions: The vascular responsiveness is altered in patients with HF and this might explain the higher prevalence of vasoplegia in this patient population.

IntroductionVasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB.Methods and analysisThis is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30.Ethics and disseminationThe trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences.Trial registration numberNCT04812717.

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