Pulmonary Hypertension in an Oncologic Intensive Care Unit

  • Lilit A. Sargsyan
  • Saadia A. FaizEmail author
Reference work entry


Pulmonary hypertension (PH) is the condition of elevated pressures in the pulmonary circulation. PH can develop acutely in patients with critical illness such as acute respiratory distress syndrome, sepsis, massive pulmonary embolism, left ventricular dysfunction, or after surgery. In a cancer patient, unique etiologies such as myeloproliferative disorders, tyrosine kinase inhibitors, or tumor emboli may result in PH. Early recognition and treatment of the causative condition may reverse acute PH or return chronic PH to its baseline status. Progression of the disease or its decompensation due to infection, a thromboembolic event, or other triggers can lead to admission to an intensive care unit. Regardless of etiology, the development or worsening of PH may precipitate hypoxemia, hemodynamic instability, or right ventricular failure, which can be challenging to manage or even fatal. In select cases, rapid institution of advanced treatment modalities may be warranted. This chapter reviews the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and prognosis of PH and presents a comprehensive analysis of PH and right heart failure management strategies in the critical care setting. In particular, a unique perspective on oncologically relevant PH is provided.


Pulmonary hypertension Intensive care Critical care Cancer Myeloproliferative disorders Pulmonary embolism Cor pulmonale PAH TKI RV failure 


  1. 1.
    Andreassen AK, Ragnarsson A, Gude E, et al. Balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension. Heart. 2013;99:1415–20.CrossRefGoogle Scholar
  2. 2.
    Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry. Chest. 2010;137:376–87.CrossRefGoogle Scholar
  3. 3.
    Barber NA, Ganti AK. Pulmonary toxicities from targeted therapies: a review. Target Oncol. 2011;6:235–43.CrossRefGoogle Scholar
  4. 4.
    Bartolome SD, Torres F. Severe pulmonary arterial hypertension: stratification of medical therapies, mechanical support, and lung transplantation. Heart Fail Rev. 2016;21:347–56.CrossRefGoogle Scholar
  5. 5.
    Bashoura L, Eapen GA, Faiz SA. Pulmonary manifestations of lymphoma and Leukemia. Clin Chest Med. 2017;38:187–200.CrossRefGoogle Scholar
  6. 6.
    Bednarczyk J, Strumpher J, Jacobsohn E. Inhaled milrinone for pulmonary hypertension in high-risk cardiac surgery: silver bullet or just part of a broader management strategy? Can J Anaesth. 2016;63:1122–7.CrossRefGoogle Scholar
  7. 7.
    Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Carlson DL, Willis MS, White DJ, et al. Tumor necrosis factor-α-induced caspase activation mediates endotoxin-related cardiac dysfunction. Crit Care Med. 2005;33:1021–8.CrossRefGoogle Scholar
  9. 9.
    Chan CM, Klilnger JR. The right ventricle in sepsis. Clin Chest Med. 2008;29(4):661–76. Scholar
  10. 10.
    Channick RN, Voswinckel R, Rubin LJ. Inhaled treprostinil: a therapeutic review. Drug Des Devel Ther. 2012;6:19–28. Scholar
  11. 11.
    Cherpanath TGV, Lagrand WK, Schultz MJ, Groeneveld ABJ. Cardiopulmonary interactions during mechanical ventilation in critically ill patients. Neth Heart J. 2013;21:166–72.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Christenson J, Lavoie A, O’connor M, et al. The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide. Am J Respir Crit Care Med. 2000;161:1443–9.CrossRefGoogle Scholar
  13. 13.
    Coz Yataco A, Aguinaga MM, Buck KP, et al. Hospital and intensive care unit management of decompensated pulmonary hypertension and right ventricular failure. Heart Fail Rev. 2016;21(3):323–46.CrossRefGoogle Scholar
  14. 14.
    D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115:343–9.CrossRefGoogle Scholar
  15. 15.
    Dandoy CE, Hirsch R, Chima R, et al. Pulmonary hypertension after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:1546–56.CrossRefGoogle Scholar
  16. 16.
    Denault AY, Bussières JS, Arellano R, et al. A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients. Can J Anaesth. 2016;63(10):1140–53. Scholar
  17. 17.
    Denault AY, Haddad F, Jacobsohn E, et al. Perioperative right ventricular dysfunction. Curr Opin Anaesthesiol. 2013;26:71–81.CrossRefGoogle Scholar
  18. 18.
    De Wet CJ, Affleck DG, Jacobsohn E, et al. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg. 2004;127:1058–67.CrossRefGoogle Scholar
  19. 19.
    Dudzinski DM, Mak GS, Hung JW. Pericardial diseases. Curr Probl Cardiol. 2012;37(3):75–118.CrossRefGoogle Scholar
  20. 20.
    Elkayam U, Ng TMH, Hatamizadeh P, et al. Renal vasodilatory action of dopamine in patients with heart failure: magnitude of effect and site of action. Circulation. 2008;117:200–5.CrossRefGoogle Scholar
  21. 21.
    Faiz SA, Iliescu C, Lopez-Mattei J, et al. Resolution of myelofibrosis-associated pulmonary arterial hypertension following allogeneic hematopoietic stem cell transplantation. Pulm Circ. 2016;6:611–3.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Freitas AF Jr, Bacal F, Oliveira Jde L Jr, et al. Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure. Arq Bras Cardiol. 2009;92:116–26.CrossRefGoogle Scholar
  23. 23.
    Galiè N, Humbert M, Vachiery J-L, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37:67–119.CrossRefGoogle Scholar
  24. 24.
    Gildea JJ. Dopamine and angiotensin as renal counterregulatory systems controlling sodium balance. Curr Opin Nephrol Hypertens. 2009;18:28–32.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Greer JR. Pathophysiology of cardiovascular dysfunction in sepsis. BJA Edu. 2015;15:316–21.CrossRefGoogle Scholar
  26. 26.
    Greyson CR. Evaluation of right ventricular function. Curr Cardiol Rep. 2011;13:194–202.CrossRefGoogle Scholar
  27. 27.
    Greyson CR. Pathophysiology of right ventricular failure. Crit Care Med. 2008;36:S57–65.CrossRefGoogle Scholar
  28. 28.
    Grignola JC, Domingo E. Acute right ventricular dysfunction in intensive care unit. Biomed Res Int. 2017;
  29. 29.
    Grinstein J, Gomberg-Maitland M. Management of pulmonary hypertension and right heart failure in the intensive care unit. Curr Hypertens Rep. 2015;17(5):32. Scholar
  30. 30.
    Guilpain P, Montani D, Damaj G, et al. Pulmonary hypertension associated with myeloproliferative disorders: a retrospective study of ten cases. Respiration. 2008;76:295–302.CrossRefGoogle Scholar
  31. 31.
    Gurghean AL, Savulescu-Fiedler I, Mihailescu A. Multiple cardiac complications after adjuvant therapy for breast cancer: the importance of echocardiography. A case report and review of the literature. Med Ultrason. 2017;19:117–20.CrossRefGoogle Scholar
  32. 32.
    Haddad F, Doyle R, Murphy DJ, et al. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and Management of Right Ventricular Failure. Circulation. 2008a;117:1717–31.CrossRefGoogle Scholar
  33. 33.
    Haddad F, Hunt SA, Rosenthal DN, et al. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008b;117:1436–48.CrossRefGoogle Scholar
  34. 34.
    Haraldsson s A, Kieler-Jensen N, Ricksten SE. The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Anesth Analg. 2001;93(6):1439–45.CrossRefGoogle Scholar
  35. 35.
    Harjola V-P, Mebazaa A, Čelutkienė J, et al. Contemporary management of acute right ventricular failure: a statement from the heart failure association and the working group on pulmonary circulation and right ventricular function of the European Society of Cardiology. Eur J Heart Fail. 2016;18:226–41.CrossRefGoogle Scholar
  36. 36.
    Hickey PM, Thompson AAR, Charalampopoulos A, et al. Bosutinib therapy resulting in severe deterioration of pre-existing pulmonary arterial hypertension. Eur Respir J. 2016;48:1514–6.CrossRefGoogle Scholar
  37. 37.
    Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D42–50.CrossRefGoogle Scholar
  38. 38.
    Hoeper MM, Galiè N, Murali S, et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2002;165:341–4.CrossRefGoogle Scholar
  39. 39.
    Hossri CAC, Almeida RL, da C, Teixeira FR, et al. Cardiopulmonary exercise testing in pulmonary hypertension. Int J Cardiovas Sci. 2016;
  40. 40.
    Hotchkiss RS, Karl IE. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA. 1992;267:1503–10.CrossRefGoogle Scholar
  41. 41.
    Hrymak C, Strumpher J, Jacobsohn E. Acute right ventricle failure in the intensive care unit: assessment and management. Can J Cardiol. 2017;33:61–71.CrossRefGoogle Scholar
  42. 42.
    Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:13S–24S.CrossRefGoogle Scholar
  43. 43.
    Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France. Am J Respir Crit Care Med. 2006;173:1023–30.CrossRefGoogle Scholar
  44. 44.
    Iyer AS, Wells JM, Vishin S, et al. CT scan-measured pulmonary artery to aorta ratio and echocardiography for detecting pulmonary hypertension in severe COPD. Chest. 2014;145:824–32.CrossRefGoogle Scholar
  45. 45.
    Jentzer JC, Mathier MA. Pulmonary hypertension in the intensive care unit. J Intensive Care Med. 2016;31:369–85.CrossRefGoogle Scholar
  46. 46.
    Kerbaul F, Rondelet B, Motte S, et al. Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure*. Crit Care Med. 2004;32:1035–40.CrossRefGoogle Scholar
  47. 47.
    Kiely DG, Elliot CA, Sabroe I, et al. Pulmonary hypertension: diagnosis and management. BMJ. 2013;
  48. 48.
    Kolkailah AA, Hirji S, Piazza G, et al. Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment of submassive pulmonary embolism. J Card Surg. 2018;33:252–9.CrossRefGoogle Scholar
  49. 49.
    Konstam MA, Kiernan MS, Bernstein D, et al. Evaluation and Management of Right-Sided Heart Failure: a scientific statement from the American Heart Association. Circulation. 2018;137:e578–622.CrossRefGoogle Scholar
  50. 50.
    Krishnan U, Mark TM, Niesvizky R, et al. Pulmonary hypertension complicating multiple myeloma. Pulm Circ. 2015;5:590–7.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Lang IM. Management of acute and chronic RV dysfunction. Eur Heart J Suppl. 2007;9:H61–7.CrossRefGoogle Scholar
  52. 52.
    Ling Y, Johnson MK, Kiely DG, et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med. 2012;186:790–6.CrossRefGoogle Scholar
  53. 53.
    Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-second official adult heart transplantation report--2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34:1244–54.CrossRefGoogle Scholar
  54. 54.
    Machado RF, Farber HW. Pulmonary hypertension associated with chronic Hemolytic Anemia and other blood disorders. Clin Chest Med. 2013;34:739–52.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Machuca TN, de Perrot M. Mechanical support for the failing right ventricle in patients with precapillary pulmonary hypertension. Circulation. 2015;132:526–36.CrossRefGoogle Scholar
  56. 56.
    Mangi MA, Rehman H, Bansal V, et al. Ultrasound assisted catheter-directed thrombolysis of acute pulmonary embolism: a review of current literature. Cureus. 2017;
  57. 57.
    McConnell MV, Solomon SD, Rayan ME, et al. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol. 1996;78:469–73.CrossRefGoogle Scholar
  58. 58.
    McGoon MD, Benza RL, Escribano-Subias P, et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol. 2013;62:D51–9.CrossRefGoogle Scholar
  59. 59.
    McGoon MD, Krichman A, Farber HW, et al. Design of the REVEAL registry for US patients with pulmonary arterial hypertension. Mayo Clin Proc. 2008;83:923–31.CrossRefGoogle Scholar
  60. 60.
    McLaughlin VV, Shah SJ, Souza R, et al. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015;65:1976–97.CrossRefGoogle Scholar
  61. 61.
    Mekontso Dessap A, Boissier F, Charron C, et al. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive Care Med. 2016;42:862–70.CrossRefGoogle Scholar
  62. 62.
    Montani D, Bergot E, Günther S, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125:2128–37.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Montani D, Lau EM, Dorfmüller P, et al. Pulmonary veno-occlusive disease. Eur Respir J. 2016;47:1518–34.CrossRefGoogle Scholar
  64. 64.
    Naeije R, Manes A. The right ventricle in pulmonary arterial hypertension. Eur Respir Rev. 2014;23:476–87.CrossRefGoogle Scholar
  65. 65.
    Oudiz RJ. Pulmonary hypertension associated with left-sided heart disease. Clin Chest Med. 2007;28:233–41.CrossRefGoogle Scholar
  66. 66.
    Peacock AJ, Murphy NF, McMurray JJV, et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J. 2007;30:104–9.CrossRefGoogle Scholar
  67. 67.
    Pengo V, Lensing AWA, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350:2257–64.CrossRefGoogle Scholar
  68. 68.
    Price LC, Dimopoulos K, Marino P, et al. The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension. Thorax. 2017;72:1035–45.CrossRefGoogle Scholar
  69. 69.
    Qiu J, Jia L, Hao Y, et al. Efficacy and safety of levosimendan in patients with acute right heart failure: a meta-analysis. Life Sci. 2017;184:30–6.CrossRefGoogle Scholar
  70. 70.
    Ranchoux B, Günther S, Quarck R, et al. Chemotherapy-induced pulmonary hypertension: role of alkylating agents. Am J Pathol. 2015;185:356–71.CrossRefGoogle Scholar
  71. 71.
    Rashdan S, Minna JD, Gerber DE. Diagnosis and management of pulmonary toxicity associated with cancer immunotherapy. Lancet Respir Med. 2018;6:472–8.CrossRefGoogle Scholar
  72. 72.
    Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017;45:486–552.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Riou M, Seferian A, Savale L, et al. Deterioration of pulmonary hypertension and pleural effusion with bosutinib following dasatinib lung toxicity. Eur Respir J. 2016;48:1517–9.CrossRefGoogle Scholar
  74. 74.
    Roberts KE, Hamele-Bena D, Saqi A, et al. Pulmonary tumor embolism: a review of the literature. Am J Med. 2003;115:228–32.CrossRefGoogle Scholar
  75. 75.
    Sahay S, Tonelli AR. Pericardial effusion in pulmonary arterial hypertension. Pulm Circ. 2013;3:467–77.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Salsano A, Sportelli E, Olivieri GM, et al. RVAD support in the setting of submassive pulmonary embolism. J Extra Corpor Technol. 2017;49:304–6.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Sandoval J, Gaspar J, Pulido T, et al. Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension. J Am Coll Cardiol. 1998;32:297–304.CrossRefGoogle Scholar
  78. 78.
    Seegobin K, Babbar A, Ferreira J, et al. A case of worsening pulmonary arterial hypertension and pleural effusions by bosutinib after prior treatment with dasatinib. Pulm Circ. 2017;7:808–12.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Shaikh AY, Shih JA. Chemotherapy-induced cardiotoxicity. Curr Heart Fail Rep. 2012;9:117–27.CrossRefGoogle Scholar
  80. 80.
    Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D34–41.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Steppan J, Diaz-Rodriguez N, Barodka VM, et al. Focused review of perioperative Care of Patients with pulmonary hypertension and proposal of a perioperative pathway. Cureus. 2018;
  82. 82.
    Strumpher J, Jacobsohn E. Pulmonary hypertension and right ventricular dysfunction: physiology and perioperative management. J Cardiothorac Vasc Anesth. 2011;25:687–704.CrossRefGoogle Scholar
  83. 83.
    Sztrymf B, Souza R, Bertoletti L, et al. Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J. 2010;35:1286–93.CrossRefGoogle Scholar
  84. 84.
    Tamura Y, Kimura M, Takei M, et al. Oral vasopressin receptor antagonist tolvaptan in right heart failure due to pulmonary hypertension. Eur Respir J. 2015;46:283–6.CrossRefGoogle Scholar
  85. 85.
    Trow TK, Christina Argento A, Rubinowitz AN, et al. A 71-year-old woman with myelofibrosis, hypoxemia, and pulmonary hypertension. Chest. 2010;138:1506–10.CrossRefGoogle Scholar
  86. 86.
    Ventetuolo CE, Klinger JR. Management of acute right ventricular failure in the intensive care unit. Ann Am Thorac Soc. 2014;11:811–22.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Vonk Noordegraaf A, Galie N. The role of the right ventricle in pulmonary arterial hypertension. Eur Respir Rev. 2011;20:243–53.CrossRefGoogle Scholar
  88. 88.
    Weinberg A, Tapson VF, Ramzy D. Massive pulmonary embolism: extracorporeal membrane oxygenation and surgical pulmonary embolectomy. Semin Respir Crit Care Med. 2017;38:66–72.CrossRefGoogle Scholar
  89. 89.
    Weinberger B, Laskin DL, Heck DE, et al. The toxicology of inhaled nitric oxide. Toxicol Sci. 2001;59:5–16.CrossRefGoogle Scholar
  90. 90.
    Weitsman T, Weisz G, Farkash R, et al. Pulmonary hypertension with left heart disease: prevalence, temporal shifts in Etiologies and outcome. Am J Med. 2017;130:1272–9.CrossRefGoogle Scholar
  91. 91.
    Westerhof BE, Saouti N, van der Laarse WJ, et al. Treatment strategies for the right heart in pulmonary hypertension. Cardiovasc Res. 2017;113:1465–73.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Yusuf SW, Venkatesulu BP, Mahadevan LS, et al. Radiation-induced cardiovascular disease: a clinical perspective. Front Cardiovasc Med. 2017;4:66. Scholar
  93. 93.
    Zamanian RT, Haddad F, Doyle RL, et al. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med. 2007;35:2037–50.CrossRefGoogle Scholar
  94. 94.
    Żyłkowska J, Kurzyna M, Florczyk M, et al. Pulmonary artery dilatation correlates with the risk of unexpected death in chronic arterial or thromboembolic pulmonary hypertension. Chest. 2012;142:1406–16.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Divisions of Critical Care, Pulmonary, and Sleep Medicine, Department of Internal MedicineMcGovern Medical School at The University of Texas Health Science Center at HoustonHoustonUSA
  2. 2.Department of Pulmonary Medicine, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA

Section editors and affiliations

  • Yenny Cardenas
    • 1
  1. 1.Critical Care DepartmentUniversidad del Rosario Hospital Universitario Fundacion Santa Fe deBogotaColombia

Personalised recommendations