Vasoplegia in the Postoperative Period After Cardiac Transplantation

  • Joshua L. Chan
  • Fardad EsmailianEmail author
Part of the Difficult Decisions in Surgery: An Evidence-Based Approach book series (DDSURGERY)


Vasoplegia syndrome is a distinct pathologic process that occurs following cardiac surgery. The use of cardiopulmonary bypass and the propagation of circulating inflammatory cytokines is believed to be a key mediator in the development of this vasodilatory shock. Heart transplantation is a known risk factor for vasoplegia, and remains a relevant concern in a vulnerable population particularly susceptible to the morbidity related to severe hemodynamic aberrations. The treatment of this complex phenomenon following cardiac transplantation can be challenging, as it is often refractory to conventional critical care. Additional strategies have been evaluated in the management of vasoplegia syndrome. Multiple trials have identified low dose arginine vasopressin infusion (0.03 U/min) as a useful treatment option in mitigating this global vasodilatory state, with a growing number of studies indicating its efficacy as a prophylactic agent as well. Investigation of methylene blue (2 mg/kg) has also demonstrated encouraging results when employed in similar circumstances. Based on the cumulative results of available studies, the use of arginine vasopressin or methylene blue is recommended in heart transplant patients without contraindications to therapy who exhibit vasoplegia syndrome refractory to conventional management techniques. In patients with multiple preoperative risk factors for vasoplegia, arginine vasopressin or methylene blue may additionally be considered as a prophylactic pharmacologic option.


Vasoplegia, low systemic vascular resistance syndrome Arginine vasopressin Methylene blue Cardiac transplantation 


  1. 1.
    Gomes WJ, Carvalho AC, Palma JH, Goncalves I Jr, Buffolo E. Vasoplegic syndrome: a new dilemma. J Thorac Cardiovasc Surg. 1994;107(3):942–3.PubMedGoogle Scholar
  2. 2.
    Shanmugam G. Vasoplegic syndrome – the role of methylene blue. Eur J Cardiothorac Surg. 2005;28(5):705–10.CrossRefGoogle Scholar
  3. 3.
    Fischer GW, Levin MA. Vasoplegia during cardiac surgery: current concepts and management. Semin Thorac Cardiovasc Surg. 2010;22(2):140–4.CrossRefGoogle Scholar
  4. 4.
    Weis F, Kilger E, Beiras-Fernandez A, et al. Association between vasopressor dependence and early outcome in patients after cardiac surgery. Anaesthesia. 2006;61(10):938–42.CrossRefGoogle Scholar
  5. 5.
    Byrne JG, Leacche M, Paul S, et al. Risk factors and outcomes for ‘vasoplegia syndrome’ following cardiac transplantation. Eur J Cardiothorac Surg. 2004;25(3):327–32.CrossRefGoogle Scholar
  6. 6.
    Boyle EM Jr, Pohlman TH, Johnson MC, Verrier ED. Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. Ann Thorac Surg. 1997;63(1):277–84.CrossRefGoogle Scholar
  7. 7.
    Carrel T, Englberger L, Mohacsi P, Neidhart P, Schmidli J. Low systemic vascular resistance after cardiopulmonary bypass: incidence, etiology, and clinical importance. J Card Surg. 2000;15(5):347–53.CrossRefGoogle Scholar
  8. 8.
    Downing SW, Edmunds LH Jr. Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg. 1992;54(6):1236–43.CrossRefGoogle Scholar
  9. 9.
    Kirklin JK. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg. 1991;51(4):529–31.CrossRefGoogle Scholar
  10. 10.
    Miller BE, Levy JH. The inflammatory response to cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11(3):355–66.CrossRefGoogle Scholar
  11. 11.
    Gillinov AM, Redmond JM, Winkelstein JA, et al. Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog. Ann Thorac Surg. 1994;57(2):345–52.CrossRefGoogle Scholar
  12. 12.
    Hosseinian L, Weiner M, Levin MA, Fischer GW. Methylene blue: magic bullet for vasoplegia? Anesth Analg. 2016;122(1):194–201.CrossRefGoogle Scholar
  13. 13.
    Kilbridge PM, Mayer JE, Newburger JW, Hickey PR, Walsh AZ, Neufeld EJ. Induction of intercellular adhesion molecule-1 and E-selectin mRNA in heart and skeletal muscle of pediatric patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1994;107(5):1183–92.PubMedGoogle Scholar
  14. 14.
    Chemmalakuzhy J, Costanzo MR, Meyer P, et al. Hypotension, acidosis, and vasodilatation syndrome post-heart transplant: prognostic variables and outcomes. J Heart Lung Transplant. 2001;20(10):1075–83.CrossRefGoogle Scholar
  15. 15.
    Levin MA, Lin HM, Castillo JG, Adams DH, Reich DL, Fischer GW. Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome. Circulation. 2009;120(17):1664–71.CrossRefGoogle Scholar
  16. 16.
    Omar S, Zedan A, Nugent K. Cardiac vasoplegia syndrome: pathophysiology, risk factors and treatment. Am J Med Sci. 2015;349(1):80–8.CrossRefGoogle Scholar
  17. 17.
    van Vessem ME, Palmen M, Couperus LE, et al. Incidence and predictors of vasoplegia after heart failure surgery. Eur J Cardiothorac Surg. 2017;51(3):532–8.PubMedGoogle Scholar
  18. 18.
    Patarroyo M, Simbaqueba C, Shrestha K, et al. Pre-operative risk factors and clinical outcomes associated with vasoplegia in recipients of orthotopic heart transplantation in the contemporary era. J Heart Lung Transplant. 2012;31(3):282–7.CrossRefGoogle Scholar
  19. 19.
    Kofidis T, Struber M, Wilhelmi M, et al. Reversal of severe vasoplegia with single-dose methylene blue after heart transplantation. J Thorac Cardiovasc Surg. 2001;122(4):823–4.CrossRefGoogle Scholar
  20. 20.
    Chan JL, Kobashigawa JA, Aintablian TL, et al. Vasoplegia after heart transplantation: outcomes at 1 year. Interact Cardiovasc Thorac Surg. 2017;25(2):212–7.CrossRefGoogle Scholar
  21. 21.
    Argenziano M, Chen JM, Choudhri AF, et al. Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg. 1998;116(6):973–80.CrossRefGoogle Scholar
  22. 22.
    Mekontso-Dessap A, Houel R, Soustelle C, Kirsch M, Thebert D, Loisance DY. Risk factors for post-cardiopulmonary bypass vasoplegia in patients with preserved left ventricular function. Ann Thorac Surg. 2001;71(5):1428–32.CrossRefGoogle Scholar
  23. 23.
    Argenziano M, Choudhri AF, Oz MC, Rose EA, Smith CR, Landry DW. A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation. 1997;96(9 Suppl):II-286–90.Google Scholar
  24. 24.
    Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345(8):588–95.CrossRefGoogle Scholar
  25. 25.
    Colson PH, Bernard C, Struck J, Morgenthaler NG, Albat B, Guillon G. Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration. Crit Care. 2011;15(5):R255.CrossRefGoogle Scholar
  26. 26.
    Bartelstone HJ, Nasmyth PA. Vasopressin potentiation of catecholamine actions in dog, rat, cat, and rat aortic strip. Am J Phys. 1965;208:754–62.CrossRefGoogle Scholar
  27. 27.
    Umino T, Kusano E, Muto S, et al. AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells. Am J Phys. 1999;276(3 Pt 2):F433–41.Google Scholar
  28. 28.
    Morales DL, Gregg D, Helman DN, et al. Arginine vasopressin in the treatment of 50 patients with postcardiotomy vasodilatory shock. Ann Thorac Surg. 2000;69(1):102–6.CrossRefGoogle Scholar
  29. 29.
    Dunser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation. 2003;107(18):2313–9.CrossRefGoogle Scholar
  30. 30.
    Hajjar LA, Vincent JL, Barbosa Gomes Galas FR, et al. Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: the VANCS randomized controlled trial. Anesthesiology. 2017;126(1):85–93.CrossRefGoogle Scholar
  31. 31.
    Morales DL, Garrido MJ, Madigan JD, et al. A double-blind randomized trial: prophylactic vasopressin reduces hypotension after cardiopulmonary bypass. Ann Thorac Surg. 2003;75(3):926–30.CrossRefGoogle Scholar
  32. 32.
    Papadopoulos G, Sintou E, Siminelakis S, Koletsis E, Baikoussis NG, Apostolakis E. Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-a double-blind randomized study. J Cardiothorac Surg. 2010;5:17.CrossRefGoogle Scholar
  33. 33.
    Lenglet S, Mach F, Montecucco F. Methylene blue: potential use of an antique molecule in vasoplegic syndrome during cardiac surgery. Expert Rev Cardiovasc Ther. 2011;9(12):1519–25.CrossRefGoogle Scholar
  34. 34.
    Schirmer RH, Adler H, Pickhardt M, Mandelkow E. Lest we forget you – methylene blue…. Neurobiol Aging. 2011;32(12):2325 e2327–16.CrossRefGoogle Scholar
  35. 35.
    Manghelli J, Brown L, Tadros HB, Munfakh NA. A reminder of methylene blue’s effectiveness in treating vasoplegic syndrome after on-pump cardiac surgery. Tex Heart Inst J. 2015;42(5):491–4.CrossRefGoogle Scholar
  36. 36.
    Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH. Methylene blue and vasoplegia: who, when, and how? Mini-Rev Med Chem. 2008;8(5):472–90.CrossRefGoogle Scholar
  37. 37.
    Yiu P, Robin J, Pattison CW. Reversal of refractory hypotension with single-dose methylene blue after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 1999;118(1):195–6.CrossRefGoogle Scholar
  38. 38.
    Pagni S, Austin EH. Use of intravenous methylene blue for the treatment of refractory hypotension after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2000;119(6):1297–8.CrossRefGoogle Scholar
  39. 39.
    Leyh RG, Kofidis T, Struber M, et al. Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass? J Thorac Cardiovasc Surg. 2003;125(6):1426–31.CrossRefGoogle Scholar
  40. 40.
    Levin RL, Degrange MA, Bruno GF, et al. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004;77(2):496–9.CrossRefGoogle Scholar
  41. 41.
    Ozal E, Kuralay E, Yildirim V, et al. Preoperative methylene blue administration in patients at high risk for vasoplegic syndrome during cardiac surgery. Ann Thorac Surg. 2005;79(5):1615–9.CrossRefGoogle Scholar
  42. 42.
    Maslow AD, Stearns G, Butala P, Schwartz CS, Gough J, Singh AK. The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass. Anesth Analg. 2006;103(1):2–8.CrossRefGoogle Scholar
  43. 43.
    Weiner MM, Lin HM, Danforth D, Rao S, Hosseinian L, Fischer GW. Methylene blue is associated with poor outcomes in vasoplegic shock. J Cardiothorac Vasc Anesth. 2013;27(6):1233–8.CrossRefGoogle Scholar
  44. 44.
    Grubb KJ, Kennedy JL, Bergin JD, Groves DS, Kern JA. The role of methylene blue in serotonin syndrome following cardiac transplantation: a case report and review of the literature. J Thorac Cardiovasc Surg. 2012;144(5):e113–6.CrossRefGoogle Scholar
  45. 45.
    Correa TD, Takala J, Jakob SM. Angiotensin II in septic shock. Crit Care. 2015;19:98.CrossRefGoogle Scholar
  46. 46.
    Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419–30.CrossRefGoogle Scholar
  47. 47.
    Derrick JR, Anderson JR, Roland BJ. Adjunctive use of a biologic pressor agent, angiotensin, in management of shock. Circulation. 1962;25:263–7.CrossRefGoogle Scholar
  48. 48.
    Del Greco F, Johnson DC. Clinical experience with angiotensin II in the treatment of shock. JAMA. 1961;178:994–9.CrossRefGoogle Scholar
  49. 49.
    Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726–34.CrossRefGoogle Scholar
  50. 50.
    Chawla LS, Busse L, Brasha-Mitchell E, et al. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014;18(5):534.CrossRefGoogle Scholar
  51. 51.
    Dellinger RP, Trzeciak S. Angiotensin II for the treatment of vasodilatory shock – promise and caution. N Engl J Med. 2017;377(5):486–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Cedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Cedars-Sinai Heart InstituteLos AngelesUSA

Personalised recommendations