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• W3138794816 abstract "Central MessageHypotension after cardiothoracic surgery is commonly due to vasodilatation. Synthetic Angiotensin II is an effective vasopressor for the management of postcardiopulmonary bypass vasoplegia.This Invited Expert Opinion provides a perspective on the following paper: N Engl J Med. 2017 Aug 3;377(5):419-430. https://doi.org/10.1056/NEJMoa1704154. Epub 2017 May 21.See Commentaries on pages 1415 and 1417. Hypotension after cardiothoracic surgery is commonly due to vasodilatation. Synthetic Angiotensin II is an effective vasopressor for the management of postcardiopulmonary bypass vasoplegia. This Invited Expert Opinion provides a perspective on the following paper: N Engl J Med. 2017 Aug 3;377(5):419-430. https://doi.org/10.1056/NEJMoa1704154. Epub 2017 May 21. See Commentaries on pages 1415 and 1417. Feature Editor Note—Vasoplegia, also known as vasodilatory, distributive, or high-output shock, is a dilemma that is frequently encountered in the cardiothoracic surgical patient. Compared with the different types of shock, vasoplegia is the most common, complex, and ubiquitous, as it can be present at a late stage of any of the other shock types, or at any stage, in intrinsically vasodilatory shock, as seen in sepsis, anaphylaxis, adrenal insufficiency, and primary vasoplegia after cardiac surgery. There has been ongoing interest in the pathophysiology of vasoplegia that has helped develop new therapeutic strategies beyond the catecholamine and arginine-vasopressin based approaches. Despite the relative common use of rescue agents such as methylene blue, high-dose hydroxycobalamin, and steroids without much scientific rigor, angiotensin II (Ang-2) has been recently introduced as a treatment for catecholamine resistant vasodilatory shock with a more comprehensive study approach. In this invited expert opinion, a multi-institutional team lead by Dr Khanna describes eloquently the unique aspects of vasoplegia in the cardiothoracic surgery patient and the reasons why Ang-2 may be considered the rescue therapeutic choice for catecholamine-resistant vasoplegia in these patients. The article starts describing the role of the renin–angiotensin cascade in vasoplegia, including the unique aspects affecting the cardiothoracic surgical patient, the multicenter randomized controlled ATHOS-3 trial, which studied the role of Ang-2 in the treatment of high-output shock, and novel concepts such as high renin shock and its potential implications for shock management. The manuscript then glances over current published data on Ang-2 and the cardiothoracic surgery patient population, including a full section on extracorporeal membrane oxygenation. Finally, the authors describe current recommendations and dosing protocols, including a brief comment on value and cost. This article brings light to a new agent that appears promising as a complement to our current management strategies of vasoplegia and opens the door for more research in this important area of perioperative care. Juan N. Pulido MD Shock is frequently encountered during cardiothoracic surgery and in the cardiothoracic surgical intensive care unit and can result from a number of etiologies, including cardiogenic, hypovolemic, hemorrhagic, obstructive, and distributive. Vasoplegia, also clinically referred to as vasodilatory shock, distributive shock, or high-output shock, occurs in 5% to 25% of patients undergoing cardiac surgery and is a form of shock characterized by decreased systemic vascular resistance and normal-to-high cardiac output.1Busse L.W. Barker N. Petersen C. Vasoplegic syndrome following cardiothoracic surgery—review of pathophysiology and update of treatment options.Crit Care. 2020; 24: 36Google Scholar,2Hajjar L.A. Vincent J.L. Barbosa Gomes Galas F.R. Rhodes A. Landoni G. Osawa E.A. et al.Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: the VANCS randomized controlled trial.Anesthesiology. 2017; 126: 85-93Google Scholar The pharmacologic treatment of vasoplegic shock in the postcardiotomy state has classically focused on interventions that modulate the sympathetic nervous and arginine–vasopressin systems. Norepinephrine (NEpi) and epinephrine are medications that target the sympathetic nervous system by binding to α1-receptors, whereas vasopressin targets the arginine–vasopressin system by binding to V1a receptors.3Chow J.H. Abuelkasem E. Sankova S. Henderson R.A. Mazzeffi M.A. Tanaka K.A. Reversal of vasodilatory shock: current perspectives on conventional, rescue, and emerging vasoactive agents for the treatment of shock.Anesth Analg. 2020; 130: 15-30Google Scholar The Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery (VANCS) trial is the only randomized control trial examining the use of NEpi and vasopressin strategies in cardiac surgery. Although there was no difference in mortality between the groups (30-day mortality 15.9% NEpi vs 15.4% vasopressin, P = .98), there was significantly less development of atrial fibrillation in those receiving vasopressin (63.8% vasopressin vs 82.1% NEpi, P = .0014), which is appealing in the postcardiotomy state.2Hajjar L.A. Vincent J.L. Barbosa Gomes Galas F.R. Rhodes A. Landoni G. Osawa E.A. et al.Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: the VANCS randomized controlled trial.Anesthesiology. 2017; 126: 85-93Google Scholar Alternative therapies such as methylene blue and hydroxycobalamin, which inhibit the production of potent vasodilatory nitric oxide, have been applied in severe vasoplegia.4Ortoleva J. Shapeton A. Vanneman M. Dalia A.A. Vasoplegia during cardiopulmonary bypass: current literature and rescue therapy options.J Cardiothorac Vasc Anesth. 2020; 34: 2766-2775Google Scholar These agents are not vasoconstrictors, have sparse supporting evidence, and are limited by increased risk for serotonin syndrome and interference with oximetry readings (methylene blue) and false blood leak alarm and interference with laboratory assays using colorimetry (hydroxycobalamin).4Ortoleva J. Shapeton A. Vanneman M. Dalia A.A. Vasoplegia during cardiopulmonary bypass: current literature and rescue therapy options.J Cardiothorac Vasc Anesth. 2020; 34: 2766-2775Google Scholar The renin–angiotensin–aldosterone system (RAAS) is a third system that has been recently studied and can be modulated with the administration of angiotensin II (Ang-2), which primarily binds to AT1 receptors to achieve vasoconstriction. Evidence for the use of Ang-2 in shock is primarily based on the ATHOS-3 randomized controlled trial, which studied patients in distributive shock who required vasopressors for more than 6 hours. The primary outcome of the study was the achievement of a target mean arterial pressure (MAP) by hour 3 of the study, which was defined an increase by 10 mm Hg from baseline, or an increase to 75 mm Hg. Although much criticism has surrounded this MAP target, this target was set deliberately in conjunction with a special protocol assessment agreement by the US Food and Drug Administration to study Ang-2 efficacy as a vasopressor (and not as a catecholamine-sparing agent) without compromising patient safety and introducing confounding variables from the de-escalation of other vasoconstrictive agents. ATHOS-3 found that, compared with placebo, patients receiving Ang-2 had a decreased NEpi-equivalent dosing requirement for background vasopressors (Table 1) (–0.03 ng/kg/min Ang-2 vs 0.03 standard of care [SOC], P < .001) and achieved the target MAP at a greater rate than those receiving SOC (69.9% Ang-2 vs 23.4% SOC, P < .001).5Khanna A. English S.W. Wang X.S. Ham K. Tumlin J. Szerlip H. et al.Angiotensin II for the treatment of vasodilatory shock.N Engl J Med. 2017; 377: 419-430Google Scholar Post-hoc analyses of ATHOS-3 found that those patients with acute kidney injury requiring renal-replacement therapy (RRT) had significantly improved 28-day mortality (51.8% Ang-2 vs 70.8% SOC, P = .037) and greater rates of liberation from RRT (38% Ang-2 vs 15% SOC, P = .007) than those receiving SOC.6Tumlin J.A. Murugan R. Deane A.M. Ostermann M. Busse L.W. Ham K.R. et al.Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II.Crit Care Med. 2018; 46: 949-957Google Scholar Patients who are Ang-2 deficient, as indicated by a high ratio of angiotensin I (Ang-1) to Ang-2, have a significantly greater risk of mortality (hazard ratio, 0.54; P = .011).7Bellomo R. Wunderink R.G. Szerlip H. English S.W. Busse L.W. Deane A.M. et al.Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock.Crit Care. 2020; 24: 43Google Scholar In addition, high levels of renin may indicate deficiencies in the RAAS, whereby the inability of angiotensin-converting enzyme (ACE) to convert Ang-1 into Ang-2 may lead to the production of vasodilatory substances such as angiotensin-(1-9) and angiotensin-(1-7).8Chawla L.S. Chen S. Bellomo R. Tidmarsh G.F. Angiotensin converting enzyme defects in shock: implications for future therapy.Crit Care. 2018; 22: 274Google Scholar The production of these byproducts leads to further decreases in MAP, which stimulates the juxtaglomerular cells of the kidney to produce additional renin.9Chow J.H. Wallis M. Lankford A.S. Chancer Z. Barth R.N. Scalea J.R. et al.Treatment of renin–angiotensin–aldosterone system dysfunction with angiotensin II in high-renin septic shock.Semin Cardiothorac Vasc Anesth. 2021; 25: 67-73Google Scholar Normal plasma renin concentration ranges from 3 to 33 pg/mL. A prespecified subanalysis of ATHOS-3 reported that high-renin shock (defined as renin levels greater than the study population median of 172.7 pg/mL) was associated with significantly greater 28-day mortality when it was treated with SOC vasopressors versus SOC vasopressors plus Ang-2 (69.9% SOC vs 50.9% Ang-2 + SOC, P = .01).10Bellomo R. Forni L.G. Busse L.W. McCurdy M.T. Ham K.R. Boldt D.W. et al.Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock.Am J Respir Crit Care Med. 2020; 202: 1253-1261Google ScholarTable 1NEpi equivalency of commonly used vasopressorsDrugDoseNEpi-equivalentNEpi0.1 μg/kg/min0.1 μg/kg/minEpinephrine0.1 μg/kg/min0.1 μg/kg/minPhenylephrine1.0 μg/kg/min0.1 μg/kg/minDopamine15 μg/kg/min0.1 μg/kg/minVasopressin0.04 units/min0.1 μg/kg/minThis conversion scale of NEpi equivalent dosing was developed based on the values used in the ATHOS-3 trial.5Khanna A. English S.W. Wang X.S. Ham K. Tumlin J. Szerlip H. et al.Angiotensin II for the treatment of vasodilatory shock.N Engl J Med. 2017; 377: 419-430Google Scholar NEpi, Norepinephrine. Open table in a new tab This conversion scale of NEpi equivalent dosing was developed based on the values used in the ATHOS-3 trial.5Khanna A. English S.W. Wang X.S. Ham K. Tumlin J. Szerlip H. et al.Angiotensin II for the treatment of vasodilatory shock.N Engl J Med. 2017; 377: 419-430Google Scholar NEpi, Norepinephrine. Because of the adverse implications associated with shock in the cardiothoracic population, we aimed to examine and summarize the evidence for the use of Ang-2 in this unique population. Many of the studies on Ang-2 have focused on the general population of patients, and only 16 of the 344 patients in the ATHOS-3 study underwent cardiac surgery (this specific subset was examined in a separate post-hoc analysis). The incidence of shock in the perioperative period for patients undergoing cardiothoracic surgery is not infrequent, and longer cardiopulmonary bypass (CPB) time is consistently associated with vasoplegia.11Dayan V. Cal R. Giangrossi F. Risk factors for vasoplegia after cardiac surgery: a meta-analysis.Interact Cardiovasc Thorac Surg. 2019; 28: 838-844Google Scholar Here, the role of the RAAS deserves special mention. ACE, responsible for the conversion of Ang-1 to Ang-2, is primarily a pulmonary capillary endothelial ectoenzyme that is compromised by lung injury.12Orfanos S.E. Armaganidis A. Glynos C. Psevdi E. Kaltsas P. Sarafidou P. et al.Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury.Circulation. 2000; 102: 2011-2018Google Scholar This clinical corollary matches the bypass of the pulmonary circulation that is a key component of cardiopulmonary bypass in cardiothoracic surgery procedures. Postcardiopulmonary bypass vasoplegia may therefore be caused by a dysfunctional ACE and a consequent low endogenous Ang-2, with an increased renin and Ang-1 and a diversion to the ACE 2 pathway, leading to an increased production of angiotensin-(1-9) and angiotensin-(1-7), which further the vasodilatory effect via the MAS and AT2 receptors and increased nitric oxide production (Figure 1). Poor clinical outcomes of high renin shock have been previously confirmed in a series of investigations, and recently a change in renin has been further strongly correlated with postcardiac surgery acute kidney injury.13Bellomo R. Forni L.G. Busse L.W. McCurdy M.T. Ham K.R. Boldt D.W. et al.Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial.Am J Respir Crit Care Med. 2020; 202: 1253-1261Google Scholar, 14Khanna A.K. Tissue perfusion and prognosis in the critically ill-is renin the new lactate?.Crit Care Med. 2019; 47: 288-290Google Scholar, 15Gleeson P.J. Crippa I.A. Mongkolpun W. Cavicchi F.Z. Van Meerhaeghe T. Brimioulle S. et al.Renin as a marker of tissue-perfusion and prognosis in critically ill patients.Crit Care Med. 2019; 47: 152-158Google Scholar, 16Kullmar M. Saadat-Gilani K. Weiss R. Massoth C. Lagan A. Núñez Cortés M. et al.Kinetic changes of plasma renin levels predict acute kidney injury in cardiac surgery patients.Am J Respir Crit Care Med. December 15, 2020; ([Epub ahead of print])Google Scholar Outside of organized clinical trials, Ang-2 has been used in vasoplegic shock associated with CPB in a number of instances (Table 2).17Bennett S.R. McKeown J. Drew P. Griffin S. Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting enzyme inhibitors.Eur J Heart Fail. 2001; 3: 587-592Google Scholar, 18Cutler N.S. Khanna A.K. Catecholamine-sparing effect of angiotensin II in an anephric patient with mixed shock after cardiac revascularization surgery: a case report.A A Pract. 2020; 14: e01266Google Scholar, 19Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google Scholar, 20Evans A. McCurdy M.T. Weiner M. Zaku B. Chow J.H. Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome.Ann Thorac Surg. 2019; 108: e5-e7Google Scholar, 21Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google Scholar, 22Thaker U. Geary V. Chalmers P. Sheikh F. Low systemic vascular resistance during cardiac surgery: case reports, brief review, and management with angiotensin II.J Cardiothorac Anesth. 1990; 4: 360-363Google Scholar, 23Trethowan B. Michaud C.J. Fifer S. Use of angiotensin II in severe vasoplegia after left pneumonectomy requiring cardiopulmonary bypass: a renin response analysis.Crit Care Med. 2020; 48: e912-e915Google Scholar, 24Wieruszewski P.M. Radosevich M.A. Kashani K.B. Daly R.C. Wittwer E.D. Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019; 33: 3080-3084Google Scholar, 25Wieruszewski P.M. Sims C.R. Daly R.C. Taner T. Wittwer E.D. Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367Google Scholar, 26Chatterjee S. Preventza O. Mousavi M. Orozco-Sevilla V. LeMaire S.A. Coselli J.S. Successful use of angiotensin II for vasoplegia after thoracoabdominal aortic aneurysm repair.J Thorac Cardiovasc Surg Tech. 2020; 4: 72-75Google Scholar, 27Ostermann M. Boldt D.W. Harper M.D. Lim G.W. Gunnerson K. Angiotensin in ECMO patients with refractory shock.Crit Care. 2018; 22: 288Google Scholar, 28Klijian A. Khanna A.K. Reddy V.S. et al.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 J Cardiothorac Vasc Anesth. 2021; 35: 51-58Google Scholar These case reports have included a wide variety of cardiothoracic surgical procedures, including coronary revascularization with and without valve intervention, isolated valve intervention, heart transplantations, combined heart/liver transplantation, lung transplantation, pneumonectomy, left ventricular assist device insertion, and thoracoabdominal aortic aneurysm repair.18Cutler N.S. Khanna A.K. Catecholamine-sparing effect of angiotensin II in an anephric patient with mixed shock after cardiac revascularization surgery: a case report.A A Pract. 2020; 14: e01266Google Scholar, 19Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google Scholar, 20Evans A. McCurdy M.T. Weiner M. Zaku B. Chow J.H. Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome.Ann Thorac Surg. 2019; 108: e5-e7Google Scholar, 21Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google Scholar, 22Thaker U. Geary V. Chalmers P. Sheikh F. Low systemic vascular resistance during cardiac surgery: case reports, brief review, and management with angiotensin II.J Cardiothorac Anesth. 1990; 4: 360-363Google Scholar, 23Trethowan B. Michaud C.J. Fifer S. Use of angiotensin II in severe vasoplegia after left pneumonectomy requiring cardiopulmonary bypass: a renin response analysis.Crit Care Med. 2020; 48: e912-e915Google Scholar, 24Wieruszewski P.M. Radosevich M.A. Kashani K.B. Daly R.C. Wittwer E.D. Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019; 33: 3080-3084Google Scholar, 25Wieruszewski P.M. Sims C.R. Daly R.C. Taner T. Wittwer E.D. Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367Google Scholar, 26Chatterjee S. Preventza O. Mousavi M. Orozco-Sevilla V. LeMaire S.A. Coselli J.S. Successful use of angiotensin II for vasoplegia after thoracoabdominal aortic aneurysm repair.J Thorac Cardiovasc Surg Tech. 2020; 4: 72-75Google Scholar Reported CPB times were variable, ranging from just over an hour to upwards of 7 hours. Similarly, vasopressor requirements, reported in NEpi equivalents, ranged from 0.20 to 3.0 μg/kg/min at the time the decision was made to institute Ang-2. All contemporary cases were already receiving vasopressin at the time of Ang-2 initiation.18Cutler N.S. Khanna A.K. Catecholamine-sparing effect of angiotensin II in an anephric patient with mixed shock after cardiac revascularization surgery: a case report.A A Pract. 2020; 14: e01266Google Scholar, 19Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google Scholar, 20Evans A. McCurdy M.T. Weiner M. Zaku B. Chow J.H. Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome.Ann Thorac Surg. 2019; 108: e5-e7Google Scholar, 21Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google Scholar,23Trethowan B. Michaud C.J. Fifer S. Use of angiotensin II in severe vasoplegia after left pneumonectomy requiring cardiopulmonary bypass: a renin response analysis.Crit Care Med. 2020; 48: e912-e915Google Scholar, 24Wieruszewski P.M. Radosevich M.A. Kashani K.B. Daly R.C. Wittwer E.D. Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019; 33: 3080-3084Google Scholar, 25Wieruszewski P.M. Sims C.R. Daly R.C. Taner T. Wittwer E.D. Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367Google Scholar, 26Chatterjee S. Preventza O. Mousavi M. Orozco-Sevilla V. LeMaire S.A. Coselli J.S. Successful use of angiotensin II for vasoplegia after thoracoabdominal aortic aneurysm repair.J Thorac Cardiovasc Surg Tech. 2020; 4: 72-75Google Scholar In many of the cases, methylene blue or hydroxycobalamin were administered before Ang-2, with resulting persistent vasoplegia leading to the decision to initiate Ang-2.18Cutler N.S. Khanna A.K. Catecholamine-sparing effect of angiotensin II in an anephric patient with mixed shock after cardiac revascularization surgery: a case report.A A Pract. 2020; 14: e01266Google Scholar,19Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google Scholar,21Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google Scholar,24Wieruszewski P.M. Radosevich M.A. Kashani K.B. Daly R.C. Wittwer E.D. Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019; 33: 3080-3084Google Scholar,25Wieruszewski P.M. Sims C.R. Daly R.C. Taner T. Wittwer E.D. Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367Google Scholar In a couple of cases, methylene blue and/or hydroxycobalamin were administered at some point after Ang-2 for reportedly additional MAP stabilization and vasopressor-sparing effects.19Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google Scholar,26Chatterjee S. Preventza O. Mousavi M. Orozco-Sevilla V. LeMaire S.A. Coselli J.S. Successful use of angiotensin II for vasoplegia after thoracoabdominal aortic aneurysm repair.J Thorac Cardiovasc Surg Tech. 2020; 4: 72-75Google Scholar All published case reports reported similar hemodynamic effects, with rapid restoration of the MAP and reduction of catecholamines and other concomitant vasoconstricting interventions. Despite many cases having a high catecholamine requirement—which is known to be associated with worse outcome—only a few deaths were reported, neither of which were deemed to be due to Ang-2 administration. Interestingly, 3 patients required extreme dosages of NEpi (3 μg/kg/min) during CPB and had Ang-2 initiated during CPB.21Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google Scholar,22Thaker U. Geary V. Chalmers P. Sheikh F. Low systemic vascular resistance during cardiac surgery: case reports, brief review, and management with angiotensin II.J Cardiothorac Anesth. 1990; 4: 360-363Google Scholar In all 3 of these cases, Ang-2 was continued into the postoperative setting. No postoperative hypotensive events were reported, and all patients were separated from vasoconstrictors quickly. Although 1 patient died from sepsis, the other 2 were discharged from the intensive care unit by postoperative day 3 despite having high catecholamine requirements and profound hypotension intraoperatively.Table 2Summary of Ang-2 use in cardiothoracic perioperative careCitationStudy typeProceduresCPB time, minPre-AngVP requirement, μg/kg/minEffectOutcomesBennett et al, 200117Bennett S.R. McKeown J. Drew P. Griffin S. Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting enzyme inhibitors.Eur J Heart Fail. 2001; 3: 587-592Google ScholarRCTn = 10∗Started during CPB and continued postoperatively.CABG (6), valve (3), CABG/valve (1)58.9 ± 17.40↑MAP and SVRINo significant change in renal functionChatterjee et al, 202026Chatterjee S. Preventza O. Mousavi M. Orozco-Sevilla V. LeMaire S.A. Coselli J.S. Successful use of angiotensin II for vasoplegia after thoracoabdominal aortic aneurysm repair.J Thorac Cardiovasc Surg Tech. 2020; 4: 72-75Google ScholarCase reportn = 1TAAA repair00.70↑MAP, VP-sparing, avoidance of spinal ischemiaDischarged alive without reported Ang-2 side effectsCutler et al, 202018Cutler N.S. Khanna A.K. Catecholamine-sparing effect of angiotensin II in an anephric patient with mixed shock after cardiac revascularization surgery: a case report.A A Pract. 2020; 14: e01266Google ScholarCase reportn = 1CABG1180.40↑MAP, VP-sparingIschemic bowel, discharged aliveCutler et al, 202019Cutler N.S. Rasmussen B.M. Bredeck J.F. Lata A.L. Khanna A.K. Angiotensin II for critically ill patients with shock after heart transplant.J Cardiothorac Vasc Anesth. August 7, 2020; ([Epub ahead of print])Google ScholarCase seriesn = 4OHT279-448Stabilized VP escalation, VP-sparingOptic neuropathy, subdural hematoma, renal failure, pneumonia, liver injuryAll discharged aliveEvans et al, 201920Evans A. McCurdy M.T. Weiner M. Zaku B. Chow J.H. Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome.Ann Thorac Surg. 2019; 108: e5-e7Google ScholarCase reportn = 1CABG1070.41↑MAP, VP sparingDischarged alive without reported Ang-2 side effectsGeary et al, 199021Geary V.M. Thaker U.N. Chalmers P.C. Sheikh F. The use of angiotensin II to treat profound hypotension in a patient taking amiodarone.J Cardiothorac Anesth. 1990; 4: 364-367Google ScholarCase reportn = 1∗Started during CPB and continued postoperatively.AVR1343.0Restoration of MAPDischarged alive without reported Ang-2 side effectsKlijian et al, 202128Klijian A. Khanna A.K. Reddy V.S. et al.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 J Cardiothorac Vasc Anesth. 2021; 35: 51-58Google ScholarPost-hocn = 9†Patients were enrolled in the ATHOS-3 trial.NRNR0.28 (0.20-0.47)↑MAP, VP-sparingOne death from cardiogenic shockOstermann et al, 201827Ostermann M. Boldt D.W. Harper M.D. Lim G.W. Gunnerson K. Angiotensin in ECMO patients with refractory shock.Crit Care. 2018; 22: 288Google ScholarCase seriesn = 7†Patients were enrolled in the ATHOS-3 trial.ECMO, aortic dissection (1)NR0.26-1.55↑MAP, VP-sparingDigital and bowel ischemia, 1 deathThaker et al, 199022Thaker U. Geary V. Chalmers P. Sheikh F. Low systemic vascular resistance during cardiac surgery: case reports, brief review, and management with angiotensin II.J Cardiothorac Anesth. 1990; 4: 360-363Google ScholarCase seriesn = 2∗Started during CPB and continued postoperatively.CABGNR3.0↑perfusion pressureDischarged alive without reported Ang-2 side effectsDeath from sepsisTrethowan et al, 202023Trethowan B. Michaud C.J. Fifer S. Use of angiotensin II in severe vasoplegia after left pneumonectomy requiring cardiopulmonary bypass: a renin response analysis.Crit Care Med. 2020; 48: e912-e915Google ScholarCase reportn = 1PneumonectomyNR0.75↑MAP, VP-sparingDischarged alive without reported Ang-2 side effectsWieruszewski et al, 201925Wieruszewski P.M. Sims C.R. Daly R.C. Taner T. Wittwer E.D. Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367Google ScholarCase reportn = 1OLT/OHT1660.22↑MAP, VP-sparingDischarged alive without reported Ang-2 side effectsWieruszewski et al, 201924Wieruszewski P.M. Radosevich M.A. Kashani K.B. Daly R.C. Wittwer E.D. Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019; 33: 3080-3084Google ScholarCase seriesn = 4OHT, CABG/AVR, BLT, LVAD/CABG142-3230.28-0.38↑MAP, VP sparingIschemic digitsOne death from withdrawal of careThree discharged aliveCPB, Cardiopulmonary bypass; Ang, angiotensin; VP, vasopressor; RCT, randomized controlled trial; CABG, coronary artery bypass grafting; MAP, mean arterial pressure; SVRI, systemic vascular resistance; TAAA, thoracoabdominal aortic aneurysm; OHT, orthotopic heart transplant; AVR, aortic valve replacement; NR, not reported; ECMO, extracorporeal membrane oxygenation; OLT, orthotopic liver transplant; BLT, bilateral lung transplant; LVAD, left ventricular assist device.∗ Started during CPB and continued postoperatively.† Patients were enrolled in the ATHOS-3 trial. Open table in a new tab CPB, Cardiopulmonary bypass; Ang, angiotensin; VP, vasopressor; RCT, randomized controlled trial; CABG, coronary artery bypass grafting; MAP, mean arterial pressure; SVRI, systemic vascular resistance; TAAA, thoracoabdominal aortic aneurysm; OHT, orthotopic heart transplant; AVR, aortic valve replacement; NR, not reported; ECMO, extracorporeal membrane oxyge" @default.
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