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Pharmacology of the Pulmonary Circulation

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Principles and Practice of Anesthesia for Thoracic Surgery

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Abstract

The pulmonary vasculature is a complex system, and studies of the effects of anesthetic drugs on this system are often contradictory. A balanced anesthetic technique with adherence to the hemodynamic goals of maintenance of right ventricular preload and right coronary artery perfusion is the safest choice for patients with PHTN. There are no absolute contraindications to most anesthetic drugs in patients with pulmonary hypertension. Inhaled pulmonary vasodilators can be used to optimize hemodynamic variables perioperatively, although effects on gas exchange are variable.

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Abbreviations

(m)PAP:

(mean) Pulmonary artery pressure

CI:

Confidence interval

CO:

Cardiac output

LAP:

Left atrial pressure

PHTN:

Pulmonary hypertension

PVB:

Paravertebral block

PVR(I):

Pulmonary vascular resistance (index)

SVR(I):

Systemic vascular resistance (index)

TEA:

Thoracic epidural analgesia

References

  1. Galiè N, Simonneau G. The fifth world symposium on pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D1–3.

    Article  PubMed  Google Scholar 

  2. Galiè N, Humbert M, Vachiéry 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(1):67–119.

    Article  PubMed  Google Scholar 

  3. Hemnes AR, Kawut SM. The right ventricle in pulmonary hypertension: from dogma to data. Am J Respir Crit Care Med. 2010;182(5):586–8.

    Article  PubMed  Google Scholar 

  4. Bootsma IT, de Lange F, Koopmans M, et al. Right ventricular function after cardiac surgery is a strong independent predictor for long-term mortality. J Cardiothorac Vasc Anesth. 2017;31(5):1656–62.

    Article  PubMed  Google Scholar 

  5. Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: predictors of perioperative morbidity and mortality. J Am Coll Cardiol. 2005;45(10):1691–9.

    Article  PubMed  Google Scholar 

  6. Lai HC, Wang KY, Lee WL, Ting CT, Liu TJ. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth. 2007;99(2):184–90.

    Article  PubMed  Google Scholar 

  7. Yang B, DeBenedictus C, Watt T, et al. The impact of concomitant pulmonary hypertension on early and late outcomes following surgery for mitral stenosis. J Thorac Cardiovasc Surg. 2016;152(2):394–400.e391.

    Article  PubMed  Google Scholar 

  8. Patel HJ, Likosky DS, Pruitt AL, Murphy ET, Theurer PF, Prager RL. Aortic valve replacement in the moderately elevated risk patient: a population-based analysis of outcomes. Ann Thorac Surg. 2016;102(5):1466–72.

    Article  PubMed  Google Scholar 

  9. Mentias A, Patel K, Patel H, et al. Effect of pulmonary vascular pressures on long-term outcome in patients with primary mitral regurgitation. J Am Coll Cardiol. 2016;67(25):2952–61.

    Article  PubMed  Google Scholar 

  10. Hoeper MM, Granton J. Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. Am J Respir Crit Care Med. 2011;184(10):1114–24.

    Article  CAS  PubMed  Google Scholar 

  11. Maxwell BG, Jackson E. Role of ketamine in the management of pulmonary hypertension and right ventricular failure. J Cardiothorac Vasc Anesth. 2012;26(3):e24–5; author reply e25–26.

    Article  CAS  PubMed  Google Scholar 

  12. Hirota K, Lambert DG. Ketamine: its mechanism(s) of action and unusual clinical uses. Br J Anaesth. 1996;77(4):441–4.

    Article  CAS  PubMed  Google Scholar 

  13. Baraka A, Harrison T, Kachachi T. Catecholamine levels after ketamine anesthesia in man. Anesth Analg. 1973;52(2):198–200.

    Article  CAS  PubMed  Google Scholar 

  14. Lundy PM, Lockwood PA, Thompson G, Frew R. Differential effects of ketamine isomers on neuronal and extraneuronal catecholamine uptake mechanisms. Anesthesiology. 1986;64(3):359–63.

    Article  CAS  PubMed  Google Scholar 

  15. Maruyama K, Maruyama J, Yokochi A, Muneyuki M, Miyasaka K. Vasodilatory effects of ketamine on pulmonary arteries in rats with chronic hypoxic pulmonary hypertension. Anesth Analg. 1995;80(4):786–92.

    CAS  PubMed  Google Scholar 

  16. Lee TS, Hou X. Vasoactive effects of ketamine on isolated rabbit pulmonary arteries. Chest. 1995;107(4):1152–5.

    Article  CAS  PubMed  Google Scholar 

  17. Dumas SJPF, Bru-Mercier G, Ranchoux B, Rücker-Martin C, Gouadon E, Vocelle M, Dorfmüller P, Fadel E, Humbert M, Cohen-Kaminsky S. Role of NMDA receptors in vascular remodelling associated to pulmonary hypertension. Eur Respir J. 2014;44(Supp 58):314.

    Google Scholar 

  18. Balfors E, Haggmark S, Nyhman H, Rydvall A, Reiz S. Droperidol inhibits the effects of intravenous ketamine on central hemodynamics and myocardial oxygen consumption in patients with generalized atherosclerotic disease. Anesth Analg. 1983;62(2):193–7.

    CAS  PubMed  Google Scholar 

  19. Levanen J, Makela ML, Scheinin H. Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium. Anesthesiology. 1995;82(5):1117–25.

    Article  CAS  PubMed  Google Scholar 

  20. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth. 1989;36(2):186–97.

    Article  CAS  PubMed  Google Scholar 

  21. Tweed WA, Minuck M, Mymin D. Circulatory responses to ketamine anesthesia. Anesthesiology. 1972;37(6):613–9.

    Article  CAS  PubMed  Google Scholar 

  22. Gooding JM, Dimick AR, Tavakoli M, Corssen G. A physiologic analysis of cardiopulmonary responses to ketamine anesthesia in noncardiac patients. Anesth Analg. 1977;56(6):813–6.

    CAS  PubMed  Google Scholar 

  23. Williams GD, Philip BM, Chu LF, et al. Ketamine does not increase pulmonary vascular resistance in children with pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation. Anesth Analg. 2007;105(6):1578–84, table of contents.

    Article  CAS  PubMed  Google Scholar 

  24. Oklu E, Bulutcu FS, Yalcin Y, Ozbek U, Cakali E, Bayindir O. Which anesthetic agent alters the hemodynamic status during pediatric catheterization? Comparison of propofol versus ketamine. J Cardiothorac Vasc Anesth. 2003;17(6):686–90.

    Article  CAS  PubMed  Google Scholar 

  25. Friesen RH, Twite MD, Nichols CS, et al. Hemodynamic response to ketamine in children with pulmonary hypertension. Paediatr Anaesth. 2016;26(1):102–8.

    Article  PubMed  Google Scholar 

  26. Heller AR, Litz RJ, Koch T. A fine balance – one-lung ventilation in a patient with Eisenmenger syndrome. Br J Anaesth. 2004;92(4):587–90.

    Article  CAS  PubMed  Google Scholar 

  27. Rees DI, Gaines GY 3rd. One-lung anesthesia – a comparison of pulmonary gas exchange during anesthesia with ketamine or enflurane. Anesth Analg. 1984;63(5):521–5.

    Article  CAS  PubMed  Google Scholar 

  28. Aye T, Milne B. Ketamine anesthesia for pericardial window in a patient with pericardial tamponade and severe COPD. Can J Anaesth. 2002;49(3):283–6.

    Article  PubMed  Google Scholar 

  29. Kopka A, McMenemin IM, Serpell MG, Quasim I. Anaesthesia for cholecystectomy in two non-parturients with Eisenmenger's syndrome. Acta Anaesthesiol Scand. 2004;48(6):782–6.

    Article  CAS  PubMed  Google Scholar 

  30. Burbridge MA, Brodt J, Jaffe RA. Ventriculoperitoneal shunt insertion under monitored anesthesia care in a patient with severe pulmonary hypertension. A A Case Rep. 2016;7(2):27–9.

    Article  PubMed  Google Scholar 

  31. Trapani G, Altomare C, Liso G, Sanna E, Biggio G. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem. 2000;7(2):249–71.

    Article  CAS  PubMed  Google Scholar 

  32. Suzuki R, Maehara R, Kobuchi S, Tanaka R, Ohkita M, Matsumura Y. Beneficial effects of gamma-aminobutyric acid on right ventricular pressure and pulmonary vascular remodeling in experimental pulmonary hypertension. Life Sci. 2012;91(13–14):693–8.

    Article  CAS  PubMed  Google Scholar 

  33. Kondo U, Kim SO, Nakayama M, Murray PA. Pulmonary vascular effects of propofol at baseline, during elevated vasomotor tone, and in response to sympathetic alpha- and beta-adrenoreceptor activation. Anesthesiology. 2001;94(5):815–23.

    Article  CAS  PubMed  Google Scholar 

  34. Edanaga M, Nakayama M, Kanaya N, Tohse N, Namiki A. Propofol increases pulmonary vascular resistance during alpha-adrenoreceptor activation in normal and monocrotaline-induced pulmonary hypertensive rats. Anesth Analg. 2007;104(1):112–8.

    Article  CAS  PubMed  Google Scholar 

  35. Kondo U, Kim SO, Murray PA. Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs. Anesthesiology. 2000;93(2):437–46.

    Article  CAS  PubMed  Google Scholar 

  36. Ouedraogo N, Mounkaila B, Crevel H, Marthan R, Roux E. Effect of propofol and etomidate on normoxic and chronically hypoxic pulmonary artery. BMC Anesthesiol. 2006;6:2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bennett JM, Ehrenfeld JM, Markham L, Eagle SS. Anesthetic management and outcomes for patients with pulmonary hypertension and intracardiac shunts and Eisenmenger syndrome: a review of institutional experience. J Clin Anesth. 2014;26(4):286–93.

    Article  PubMed  Google Scholar 

  38. Colvin MP, Savege TM, Newland PE, et al. Cardiorespiratory changes following induction of anaesthesia with etomidate in patients with cardiac disease. Br J Anaesth. 1979;51(6):551–6.

    Article  CAS  PubMed  Google Scholar 

  39. Sarkar M, Laussen PC, Zurakowski D, Shukla A, Kussman B, Odegard KC. Hemodynamic responses to etomidate on induction of anesthesia in pediatric patients. Anesth Analg. 2005;101(3):645–50, table of contents.

    Article  CAS  PubMed  Google Scholar 

  40. Coskun D, Mahli A, Korkmaz S, et al. Anaesthesia for caesarean section in the presence of multivalvular heart disease and severe pulmonary hypertension: a case report. Cases J. 2009;2:9383.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lazol JP, Lichtenstein SE, Jooste EH, et al. Effect of dexmedetomidine on pulmonary artery pressure after congenital cardiac surgery: a pilot study. Pediatr Crit Care Med. 2010;11(5):589–92.

    Article  PubMed  Google Scholar 

  42. Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res. 2011;5(2):128–33.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hentrich F, Gothert M, Greschuchna D. Noradrenaline release in the human pulmonary artery is modulated by presynaptic alpha 2-adrenoceptors. J Cardiovasc Pharmacol. 1986;8(3):539–44.

    Article  CAS  PubMed  Google Scholar 

  44. De Mey J, Vanhoutte PM. Uneven distribution of postjunctional alpha 1-and alpha 2-like adrenoceptors in canine arterial and venous smooth muscle. Circ Res. 1981;48(6 Pt 1):875–84.

    Article  PubMed  Google Scholar 

  45. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology. 1992;77(6):1134–42.

    Article  CAS  PubMed  Google Scholar 

  46. Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology. 1992;77(6):1125–33.

    Article  CAS  PubMed  Google Scholar 

  47. Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.

    Article  CAS  PubMed  Google Scholar 

  48. Friesen RH, Nichols CS, Twite MD, et al. The hemodynamic response to dexmedetomidine loading dose in children with and without pulmonary hypertension. Anesth Analg. 2013;117(4):953–9.

    Article  CAS  PubMed  Google Scholar 

  49. Sharp DB, Wang X, Mendelowitz D. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Brain Res. 2014;1574:1–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kernan S, Rehman S, Meyer T, Bourbeau J, Caron N, Tobias JD. Effects of dexmedetomidine on oxygenation during one-lung ventilation for thoracic surgery in adults. J Minim Access Surg. 2011;7(4):227–31.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Bhargava HN, Villar VM, Cortijo J, Morcillo EJ. Binding of [3H][D-Ala2, MePhe4, Gly-ol5] enkephalin, [3H][D-Pen2, D-Pen5]enkephalin, and [3H]U-69,593 to airway and pulmonary tissues of normal and sensitized rats. Peptides. 1997;18(10):1603–8.

    Article  CAS  PubMed  Google Scholar 

  52. Peng P, Huang LY, Li J, et al. Distribution of kappa-opioid receptor in the pulmonary artery and its changes during hypoxia. Anat Rec (Hoboken). 2009;292(7):1062–7.

    Article  Google Scholar 

  53. Zhang L, Li J, Shi Q, et al. Role of kappa-opioid receptor in hypoxic pulmonary artery hypertension and its underlying mechanism. Am J Ther. 2013;20(4):329–36.

    Article  CAS  PubMed  Google Scholar 

  54. Kaye AD, Hoover JM, Kaye AJ, et al. Morphine, opioids, and the feline pulmonary vascular bed. Acta Anaesthesiol Scand. 2008;52(7):931–7.

    Article  CAS  PubMed  Google Scholar 

  55. Greenberg S, McGowan C, Xie J, Summer WR. Selective pulmonary and venous smooth muscle relaxation by furosemide: a comparison with morphine. J Pharmacol Exp Ther. 1994;270(3):1077–85.

    CAS  PubMed  Google Scholar 

  56. Du H, Orii R, Yamada Y, et al. Pancuronium increases pulmonary arterial pressure in lung injury. Br J Anaesth. 1996;77(4):526–9.

    Article  CAS  PubMed  Google Scholar 

  57. Hou VY, Hirshman CA, Emala CW. Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. Anesthesiology. 1998;88(3):744–50.

    Article  CAS  PubMed  Google Scholar 

  58. Norel X, Walch L, Costantino M, et al. M1 and M3 muscarinic receptors in human pulmonary arteries. Br J Pharmacol. 1996;119(1):149–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. McCoy EP, Maddineni VR, Elliott P, Mirakhur RK, Carson IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium. Can J Anaesth. 1993;40(8):703–8.

    Article  CAS  PubMed  Google Scholar 

  60. Searle NR, Thomson I, Dupont C, et al. A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 1999;13(1):20–5.

    Article  CAS  PubMed  Google Scholar 

  61. Kobayashi Y, Amenta F. Neurotransmitter receptors in the pulmonary circulation with particular emphasis on pulmonary endothelium. J Auton Pharmacol. 1994;14(2):137–64.

    Article  CAS  PubMed  Google Scholar 

  62. Barnes PJ, Liu SF. Regulation of pulmonary vascular tone. Pharmacol Rev. 1995;47(1):87–131.

    CAS  PubMed  Google Scholar 

  63. Greenberg B, Rhoden K, Barnes PJ. Endothelium-dependent relaxation of human pulmonary arteries. Am J Phys. 1987;252(2 Pt 2):H434–8.

    CAS  Google Scholar 

  64. Pearl RG, Maze M, Rosenthal MH. Pulmonary and systemic hemodynamic effects of central venous and left atrial sympathomimetic drug administration in the dog. J Cardiothorac Anesth. 1987;1(1):29–35.

    Article  CAS  PubMed  Google Scholar 

  65. Roscher R, Ingemansson R, Algotsson L, Sjoberg T, Steen S. Effects of dopamine in lung-transplanted pigs at 32 degrees C. Acta Anaesthesiol Scand. 1999;43(7):715–21.

    Article  CAS  PubMed  Google Scholar 

  66. Kwak YL, Lee CS, Park YH, Hong YW. The effect of phenylephrine and norepinephrine in patients with chronic pulmonary hypertension*. Anaesthesia. 2002;57(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  67. Vlahakes GJ, Turley K, Hoffman JI. The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations. Circulation. 1981;63(1):87–95.

    Article  CAS  PubMed  Google Scholar 

  68. Jin HK, Yang RH, Chen YF, Thornton RM, Jackson RM, Oparil S. Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia. J Appl Physiol. 1989;66(1):151–60.

    Article  CAS  PubMed  Google Scholar 

  69. Leather HA, Segers P, Berends N, Vandermeersch E, Wouters PF. Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med. 2002;30(11):2548–52.

    Article  CAS  PubMed  Google Scholar 

  70. Tayama E, Ueda T, Shojima T, et al. Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interact Cardiovasc Thorac Surg. 2007;6(6):715–9.

    Article  PubMed  Google Scholar 

  71. Price LC, Forrest P, Sodhi V, et al. Use of vasopressin after Caesarean section in idiopathic pulmonary arterial hypertension. Br J Anaesth. 2007;99(4):552–5.

    Article  CAS  PubMed  Google Scholar 

  72. Currigan DA, Hughes RJ, Wright CE, Angus JA, Soeding PF. Vasoconstrictor responses to vasopressor agents in human pulmonary and radial arteries: an in vitro study. Anesthesiology. 2014;121(5):930–6.

    Article  CAS  PubMed  Google Scholar 

  73. Jiang C, Qian H, Luo S, et al. Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation. Basic Res Cardiol. 2017;112(3):21.

    Article  PubMed  CAS  Google Scholar 

  74. Dube L, Granry JC. The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth. 2003;50(7):732–46.

    Article  PubMed  Google Scholar 

  75. Fullerton DA, Hahn AR, Agrafojo J, Sheridan BC, McIntyre RC Jr. Magnesium is essential in mechanisms of pulmonary vasomotor control. J Surg Res. 1996;63(1):93–7.

    Article  CAS  PubMed  Google Scholar 

  76. al-Halees Z, Afrane B, el-Barbary M. Magnesium sulfate to facilitate weaning of nitric oxide in pulmonary hypertension. Ann Thorac Surg. 1997;63(1):298–9.

    Article  CAS  PubMed  Google Scholar 

  77. Haas NA, Kemke J, Schulze-Neick I, Lange PE. Effect of increasing doses of magnesium in experimental pulmonary hypertension after acute pulmonary embolism. Intensive Care Med. 2004;30(11):2102–9.

    Article  PubMed  Google Scholar 

  78. Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2007;3:CD005588.

    Google Scholar 

  79. Nakayama M, Kondo U, Murray PA. Pulmonary vasodilator response to adenosine triphosphate-sensitive potassium channel activation is attenuated during desflurane but preserved during sevoflurane anesthesia compared with the conscious state. Anesthesiology. 1998;88(4):1023–35.

    Article  CAS  PubMed  Google Scholar 

  80. Priebe HJ. Differential effects of isoflurane on regional right and left ventricular performances, and on coronary, systemic, and pulmonary hemodynamics in the dog. Anesthesiology. 1987;66(3):262–72.

    Article  CAS  PubMed  Google Scholar 

  81. Kerbaul F, Bellezza M, Mekkaoui C, et al. Sevoflurane alters right ventricular performance but not pulmonary vascular resistance in acutely instrumented anesthetized pigs. J Cardiothorac Vasc Anesth. 2006;20(2):209–16.

    Article  PubMed  Google Scholar 

  82. Cheng DC, Edelist G. Isoflurane and primary pulmonary hypertension. Anaesthesia. 1988;43(1):22–4.

    Article  CAS  PubMed  Google Scholar 

  83. Rorie DK, Tyce GM, Sill JC. Increased norepinephrine release from dog pulmonary artery caused by nitrous oxide. Anesth Analg. 1986;65(6):560–4.

    Article  CAS  PubMed  Google Scholar 

  84. Schulte-Sasse U, Hess W, Tarnow J. Pulmonary vascular responses to nitrous oxide in patients with normal and high pulmonary vascular resistance. Anesthesiology. 1982;57(1):9–13.

    Article  CAS  PubMed  Google Scholar 

  85. Konstadt SN, Reich DL, Thys DM. Nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction in patients with mitral valvular disease. Can J Anaesth. 1990;37(6):613–7.

    Article  CAS  PubMed  Google Scholar 

  86. Myles PS, Leslie K, Chan MT, et al. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial. Lancet. 2014;384(9952):1446–54.

    Article  CAS  PubMed  Google Scholar 

  87. Leslie K, Myles PS, Kasza J, et al. Nitrous oxide and serious long-term morbidity and mortality in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial. Anesthesiology. 2015;123(6):1267–80.

    Article  CAS  PubMed  Google Scholar 

  88. Houfflin Debarge V, Sicot B, Jaillard S, et al. The mechanisms of pain-induced pulmonary vasoconstriction: an experimental study in fetal lambs. Anesth Analg. 2007;104(4):799–806.

    Article  PubMed  Google Scholar 

  89. Veering BT, Cousins MJ. Cardiovascular and pulmonary effects of epidural anaesthesia. Anaesth Intensive Care. 2000;28(6):620–35.

    CAS  PubMed  Google Scholar 

  90. Wink J, de Wilde RB, Wouters PF, et al. Thoracic epidural anesthesia reduces right ventricular systolic function with maintained ventricular-pulmonary coupling. Circulation. 2016;134(16):1163–75.

    Article  CAS  PubMed  Google Scholar 

  91. Garutti I, Olmedilla L, Cruz P, Pineiro P, De la Gala F, Cirujano A. Comparison of the hemodynamic effects of a single 5 mg/kg dose of lidocaine with or without epinephrine for thoracic paravertebral block. Reg Anesth Pain Med. 2008;33(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  92. Armstrong P. Thoracic epidural anaesthesia and primary pulmonary hypertension. Anaesthesia. 1992;47(6):496–9.

    Article  CAS  PubMed  Google Scholar 

  93. Mallampati SR. Low thoracic epidural anaesthesia for elective cholecystectomy in a patient with congenital heart disease and pulmonary hypertension. Can Anaesth Soc J. 1983;30(1):72–6.

    Article  CAS  PubMed  Google Scholar 

  94. Swamy MC, Mukherjee A, Rao LL, Pandith S. Anaesthetic management of a patient with severe pulmonary arterial hypertension for renal transplantation. Indian J Anaesth. 2017;61(2):167–9.

    Article  PubMed  PubMed Central  Google Scholar 

  95. 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(6):1286–93.

    Article  CAS  PubMed  Google Scholar 

  96. Fox DL, Stream AR, Bull T. Perioperative management of the patient with pulmonary hypertension. Semin Cardiothorac Vasc Anesth. 2014;18(4):310–8.

    Article  PubMed  Google Scholar 

  97. Vonk-Noordegraaf A, Haddad F, Chin KM, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62(S):D22–33.

    Article  PubMed  Google Scholar 

  98. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008;117(11):1436–48.

    Article  PubMed  Google Scholar 

  99. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993;329(27):2002–12.

    Article  CAS  PubMed  Google Scholar 

  100. Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature. 1994;368(6474):850–3.

    Article  CAS  PubMed  Google Scholar 

  101. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–67.

    Article  CAS  PubMed  Google Scholar 

  102. Troncy E, Collet JP, Shapiro S, et al. Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1483–8.

    Article  CAS  PubMed  Google Scholar 

  103. Michael JR, Barton RG, Saffle JR, et al. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1372–80.

    Article  CAS  PubMed  Google Scholar 

  104. Solina AR, Ginsberg SH, Papp D, et al. Response to nitric oxide during adult cardiac surgery. J Investig Surg. 2002;15(1):5–14.

    Article  Google Scholar 

  105. Solina AR, Ginsberg SH, Papp D, et al. Dose response to nitric oxide in adult cardiac surgery patients. J Clin Anesth. 2001;13(4):281–6.

    Article  CAS  PubMed  Google Scholar 

  106. Bigatello LM, Hess D, Dennehy KC, Medoff BD, Hurford WE. Sildenafil can increase the response to inhaled nitric oxide. Anesthesiology. 2000;92(6):1827–9.

    Article  CAS  PubMed  Google Scholar 

  107. Dias-Junior CA, Montenegro MF, Florencio BC, Tanus-Santos JE. Sildenafil improves the beneficial haemodynamic effects of intravenous nitrite infusion during acute pulmonary embolism. Basic Clin Pharmacol Toxicol. 2008;103(4):374–9.

    Article  PubMed  CAS  Google Scholar 

  108. Suntharalingam J, Hughes RJ, Goldsmith K, et al. Acute haemodynamic responses to inhaled nitric oxide and intravenous sildenafil in distal chronic thromboembolic pulmonary hypertension (CTEPH). Vasc Pharmacol. 2007;46(6):449–55.

    Article  CAS  Google Scholar 

  109. Roberts JD Jr, Fineman JR, Morin FC 3rd, et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group. N Engl J Med. 1997;336(9):605–10.

    Article  CAS  PubMed  Google Scholar 

  110. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS). Pediatrics. 1997;99(6):838–45.

    Google Scholar 

  111. Ardehali A, Hughes K, Sadeghi A, et al. Inhaled nitric oxide for pulmonary hypertension after heart transplantation. Transplantation. 2001;72(4):638–41.

    Article  CAS  PubMed  Google Scholar 

  112. Adhikari N, Granton JT. Inhaled nitric oxide for acute lung injury: no place for NO? JAMA. 2004;291(13):1629–31.

    Article  CAS  PubMed  Google Scholar 

  113. Paniagua MJ, Crespo-Leiro MG, Rodriguez JA, et al. Usefulness of nitric oxide inhalation for management of right ventricular failure after heart transplantation in patients with pretransplant pulmonary hypertension. Transplant Proc. 1999;31(6):2505–6.

    Article  CAS  PubMed  Google Scholar 

  114. Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA. Inhaled nitric oxide reduces human lung allograft dysfunction. J Thorac Cardiovasc Surg. 1996;111(5):913–9.

    Article  CAS  PubMed  Google Scholar 

  115. Yamashita H, Akamine S, Sumida Y, et al. Inhaled nitric oxide attenuates apoptosis in ischemia-reperfusion injury of the rabbit lung. Ann Thorac Surg. 2004;78(1):292–7.

    Article  PubMed  Google Scholar 

  116. Meade MO, Granton JT, Matte-Martyn A, et al. A randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation. Am J Respir Crit Care Med. 2003;167(11):1483–9.

    Article  PubMed  Google Scholar 

  117. Wilson WC, Kapelanski DP, Benumof JL, Newhart JW 2nd, Johnson FW, Channick RN. Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does not decrease pulmonary vascular resistance or improve oxygenation in normal patients. J Cardiothorac Vasc Anesth. 1997;11(2):172–6.

    Article  CAS  PubMed  Google Scholar 

  118. Ismail-Zade IA, Vuylsteke A, Ghosh S, Latimer RD. Inhaled nitric oxide and one-lung ventilation in the lateral decubitus position. J Cardiothorac Vasc Anesth. 1997;11(7):926–7.

    Article  CAS  PubMed  Google Scholar 

  119. Rocca GD, Coccia C, Pompei L, et al. Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide and inhaled aerosolized prostacyclin. J Cardiothorac Vasc Anesth. 2001;15(2):224–7.

    Article  CAS  PubMed  Google Scholar 

  120. Rocca GD, Passariello M, Coccia C, et al. Inhaled nitric oxide administration during one-lung ventilation in patients undergoing thoracic surgery. J Cardiothorac Vasc Anesth. 2001;15(2):218–23.

    Article  CAS  PubMed  Google Scholar 

  121. Ghofrani HA, Voswinckel R, Reichenberger F, et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J Am Coll Cardiol. 2004;44(7):1488–96.

    CAS  PubMed  Google Scholar 

  122. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation. 2002;105(20):2398–403.

    Article  CAS  PubMed  Google Scholar 

  123. Archer SL, Michelakis ED. Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension. N Engl J Med. 2009;361(19):1864–71.

    Article  CAS  PubMed  Google Scholar 

  124. Wharton J, Strange JW, Moller GM, et al. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med. 2005;172(1):105–13.

    Article  PubMed  Google Scholar 

  125. Galie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–903.

    Article  CAS  PubMed  Google Scholar 

  126. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–57.

    Article  CAS  PubMed  Google Scholar 

  127. Nagendran J, Archer SL, Soliman D, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116(3):238–48.

    Article  CAS  PubMed  Google Scholar 

  128. Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology. 1999;91(1):307–10.

    Article  CAS  PubMed  Google Scholar 

  129. Boffini M, Sansone F, Ceresa F, et al. Role of oral sildenafil in the treatment of right ventricular dysfunction after heart transplantation. Transplant Proc. 2009;41(4):1353–6.

    Article  CAS  PubMed  Google Scholar 

  130. De Santo LS, Mastroianni C, Romano G, et al. Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients. Transplant Proc. 2008;40(6):2015–8.

    Article  PubMed  CAS  Google Scholar 

  131. Ghofrani HA, Schermuly RT, Rose F, et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2003;167(8):1139–41.

    Article  PubMed  Google Scholar 

  132. Nagaya N, Sasaki N, Ando M, et al. Prostacyclin therapy before pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension. Chest. 2003;123(2):338–43.

    Article  CAS  PubMed  Google Scholar 

  133. Jensen KW, Kerr KM, Fedullo PF, et al. Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Circulation. 2009;120(13):1248–54.

    Article  PubMed  Google Scholar 

  134. Delcroix M, Lang I, Pepke-Zaba J, et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation. 2016;133(9):859–71.

    Article  CAS  PubMed  Google Scholar 

  135. Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116(14):1555–62.

    Article  CAS  PubMed  Google Scholar 

  136. Andersen MJ, Ersbøll M, Axelsson A, et al. Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction: the Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction (SIDAMI) trial. Circulation. 2013;127(11):1200–8.

    Article  CAS  PubMed  Google Scholar 

  137. Borgdorff MAJ, Bartelds B, Dickinson MG, et al. Sildenafil treatment in established right ventricular dysfunction improves diastolic function and attenuates interstitial fibrosis independent from afterload. Am J Physiol Heart Circ Physiol. 2014;307(3):H361–9.

    Article  CAS  PubMed  Google Scholar 

  138. Guazzi M, Bandera F, Forfia P. Sildenafil and exercise capacity in heart failure. JAMA. 2013;310(4):432.

    Article  CAS  PubMed  Google Scholar 

  139. Shim JK, Choi YS, Oh YJ, Kim DH, Hong YW, Kwak YL. Effect of oral sildenafil citrate on intraoperative hemodynamics in patients with pulmonary hypertension undergoing valvular heart surgery. J Thorac Cardiovasc Surg. 2006;132(6):1420–5.

    Article  CAS  PubMed  Google Scholar 

  140. Califf RM, Adams KF, McKenna WJ, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134(1):44–54.

    Article  CAS  PubMed  Google Scholar 

  141. Vachiéry J-L, Adir Y, Barberà JA, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D100–8.

    Article  PubMed  Google Scholar 

  142. Hambly N, Granton J. Riociguat for the treatment of pulmonary hypertension. Expert Rev Respir Med. 2015;9(6):679–95.

    Article  CAS  PubMed  Google Scholar 

  143. Ghofrani H-A, Humbert M, Langleben D, et al. Riociguat: mode of action and clinical development in pulmonary hypertension. Chest. 2017;151(2):468–80.

    Article  PubMed  Google Scholar 

  144. Ghofrani H-A, D’Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369(4):319–29.

    Article  CAS  PubMed  Google Scholar 

  145. Ghofrani H-A, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–40.

    Article  CAS  PubMed  Google Scholar 

  146. Galiè N, Müller K, Scalise A-V, Grünig E. PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension. Eur Respir J. 2015;45(5):1314–22.

    Article  PubMed  CAS  Google Scholar 

  147. Dupuis J, Jasmin JF, Prie S, Cernacek P. Importance of local production of endothelin-1 and of the ET(B)Receptor in the regulation of pulmonary vascular tone. Pulm Pharmacol Ther. 2000;13(3):135–40.

    Article  CAS  PubMed  Google Scholar 

  148. Merkus D, Houweling B, Mirza A, Boomsma F, van den Meiracker AH, Duncker DJ. Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation. Cardiovasc Res. 2003;59(3):745–54.

    Article  CAS  PubMed  Google Scholar 

  149. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126:14S–34S.

    Article  PubMed  Google Scholar 

  150. Galiè N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60–72.

    Article  PubMed  Google Scholar 

  151. Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–18.

    Article  CAS  PubMed  Google Scholar 

  152. Aversa M, Porter S, Granton J. Comparative safety and tolerability of endothelin receptor antagonists in pulmonary arterial hypertension. Drug Saf. 2015;38(5):419–35.

    Article  CAS  PubMed  Google Scholar 

  153. Galiè N, Barberà JA, Frost AE, et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015;373(9):834–44.

    Article  PubMed  CAS  Google Scholar 

  154. Buckley MS, Feldman JP. Nebulized milrinone use in a pulmonary hypertensive crisis. Pharmacotherapy. 2007;27(12):1763–6.

    Article  CAS  PubMed  Google Scholar 

  155. Lamarche Y, Perrault LP, Maltais S, Tetreault K, Lambert J, Denault AY. Preliminary experience with inhaled milrinone in cardiac surgery. Eur J Cardiothorac Surg. 2007;31(6):1081–7.

    Article  PubMed  Google Scholar 

  156. Urdaneta F, Lobato EB, Beaver T, et al. Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog. Perfusion. 2008;23(2):117–25.

    Article  CAS  PubMed  Google Scholar 

  157. 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, table of contents

    Article  PubMed  Google Scholar 

  158. Lakshminrusimha S, Porta NF, Farrow KN, et al. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med. 2009;10(1):106–12.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Moncada S, Higgs EA. Prostaglandins in the pathogenesis and prevention of vascular disease. Blood Rev. 1987;1(2):141–5.

    Article  CAS  PubMed  Google Scholar 

  160. Granton J, Moric J. Pulmonary vasodilators – treating the right ventricle. Anesthesiol Clin. 2008;26(2):337–53. vii

    Article  PubMed  Google Scholar 

  161. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med. 2000;342(25):1866–70.

    Article  CAS  PubMed  Google Scholar 

  162. Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Ann Intern Med. 2000;132(6):435–43.

    Article  CAS  PubMed  Google Scholar 

  163. Fiser SM, Cope JT, Kron IL, et al. Aerosolized prostacyclin (epoprostenol) as an alternative to inhaled nitric oxide for patients with reperfusion injury after lung transplantation. J Thorac Cardiovasc Surg. 2001;121(5):981–2.

    Article  CAS  PubMed  Google Scholar 

  164. Langer F, Wendler O, Wilhelm W, Tscholl D, Schafers HJ. Treatment of a case of acute right heart failure by inhalation of iloprost, a long-acting prostacyclin analogue. Eur J Anaesthesiol. 2001;18(11):770–3.

    Article  CAS  PubMed  Google Scholar 

  165. Langer F, Wilhelm W, Lausberg H, Schafers HJ. [Iloprost and selective pulmonary vasodilation. Clinical results of intraoperative and postoperative inhalation of iloprost]. Anaesthesist. 2004;53(8):753–8.

    Google Scholar 

  166. Sablotzki A, Hentschel T, Gruenig E, et al. Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance. Eur J Cardiothorac Surg. 2002;22(5):746–52.

    Article  PubMed  Google Scholar 

  167. Wensel R, Opitz CF, Ewert R, Bruch L, Kleber FX. Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation. 2000;101(20):2388–92.

    Article  CAS  PubMed  Google Scholar 

  168. Khan TA, Schnickel G, Ross D, et al. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg. 2009;138(6):1417–24.

    Article  CAS  PubMed  Google Scholar 

  169. McGinn K, Reichert MA. Comparison of inhaled nitric oxide versus inhaled epoprostenol for acute pulmonary hypertension following cardiac surgery. Ann Pharmacother. 2016;50(1):22–6.

    Article  CAS  PubMed  Google Scholar 

  170. Torbic H, Szumita PM, Anger KE, Nuccio P, LaGambina S, Weinhouse G. Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients. J Crit Care. 2013;28(5):844–8.

    Article  CAS  PubMed  Google Scholar 

  171. Voswinckel R, Reichenberger F, Enke B, et al. Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Pulm Pharmacol Ther. 2008;21(5):824–32.

    Article  CAS  PubMed  Google Scholar 

  172. Bund M, Henzler D, Walz R, Rossaint R, Piepenbrock S. Cardiopulmonary effects of intravenous prostaglandin E1 during experimental one-lung ventilation. Thorac Cardiovasc Surg. 2006;54(5):341–7.

    Article  CAS  PubMed  Google Scholar 

  173. Bund M, Henzler D, Walz R, Rossaint R, Piepenbrock S, Kuhlen R. [Aerosolized and intravenous prostacyclin during one-lung ventilation. Hemodynamic and pulmonary effects]. Anaesthesist. 2004;53(7):612–20.

    Google Scholar 

  174. Chen TL, Ueng TH, Huang CH, Chen CL, Huang FY, Lin CJ. Improvement of arterial oxygenation by selective infusion of prostaglandin E1 to ventilated lung during one-lung ventilation. Acta Anaesthesiol Scand. 1996;40(1):7–13.

    Article  CAS  PubMed  Google Scholar 

  175. Haraldsson A, Kieler-Jensen N, Wadenvik H, Ricksten SE. Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass. Intensive Care Med. 2000;26(2):188–94.

    Article  CAS  PubMed  Google Scholar 

  176. Nielsen VG. Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography. Anesth Analg. 2001;92(2):320–3.

    Article  CAS  PubMed  Google Scholar 

  177. Hill LL, De Wet CJ, Jacobsohn E, Leighton BL, Tymkew H. Peripartum substitution of inhaled for intravenous prostacyclin in a patient with primary pulmonary hypertension. Anesthesiology. 2004;100(6):1603–5.

    Article  PubMed  Google Scholar 

  178. 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(4):1058–67.

    Article  PubMed  CAS  Google Scholar 

  179. Cornfield DN, Milla CE, Haddad IY, Barbato JE, Park SJ. Safety of inhaled nitric oxide after lung transplantation. J Heart Lung Transplant. 2003;22(8):903–7.

    Article  PubMed  Google Scholar 

  180. Elmi-Sarabi M, Deschamps A, Delisle S, et al. Aerosolized vasodilators for the treatment of pulmonary hypertension in cardiac surgical patients: a systematic review and meta-analysis. Anesth Analg. 2017;125(2):393–402; Publish Ahead of Print:1.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology and Perioperative Medicine, Kingston Health Sciences Centre, Kingston, ON, Canada

    Cara Reimer

  2. Division of Respirology, Department of Medicine, University of Toronto and University Health Network, Mount Sinai Hospital, Women’s College Hospital, Toronto, ON, Canada

    John Granton

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  1. Cara Reimer
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Editors and Affiliations

  1. Department of Anesthesiology, University of Toronto, Toronto, ON, Canada

    Peter Slinger

Clinical Case Study

Clinical Case Study

A 46-year-old woman with interstitial lung disease (ILD) presents to the pre-anesthetic clinic before an open lung biopsy.

What are the Anesthetic Considerations for This Case?

Considerations include those of ILD and the proposed case itself. In regard to the ILD, its etiology and severity (including associated connective tissue disorders and multisystem involvement), and associated right heart dysfunction should be delineated. In regard to the biopsy, the usual considerations of lung separation, analgesic options, invasive monitoring and, in this patient, the potential requirement for perioperative inhaled vasodilator therapy are present.

Besides the Usual Anesthetic History and Physical, What Would You Want to Elicit on History and Look for on Physical Exam in This Case?

On history, a careful assessment of functional status and current symptoms, personal and family history of connective tissue diseases should be undertaken.

On physical exam, vital signs including respiratory rate, potential clubbing, crackles on lung auscultation, and signs of right heart dysfunction (including increased JVP, hepatomegaly, lower extremity edema, increased P2 on heart auscultation and right ventricular heave on palpation) should be assessed.

The patient has been experiencing progressive worsening of shortness of breath for approximately 2 years. Her ability to exercise has declined markedly, to the point where she cannot climb a flight of stairs. She had a recent admission to hospital where she was started on home oxygen therapy and referred to a respirologist. An echocardiogram done at that time revealed an RVSP of 89 with mild right ventricular dilation and hypokinesis. ECG shows sinus tachycardia at 105. The respirologist suggests a biopsy to shed light on the etiology.

Physical exam reveals a thin woman with a respiratory rate of 18 wearing oxygen via nasal prongs at 4 L/min. Her oxygen saturation is 95%, her heart rate is 95, and her blood pressure is 100/60. Airway exam is reassuring. She has coarse crackles bilaterally. JVP is normal, but P2 is increased on cardiac auscultation. There is no hepatomegaly or pedal edema.

What Can be Done to Optimize These Patients’ Perioperative Course?

After communicating with the patient’s respirologist, a decision is made to bring the patient to the hospital the day before the planned operation to perform a right heart catheterization and assess the patient’s response to inhaled prostacyclin. A pulmonary artery catheter is inserted under local anesthesia in the intensive care unit. PAP is 75/40. Systemic blood pressure is 90/60. After institution of inhaled prostacyclin, the PAP decreases to 60/30 with no change in systemic pressure.

What is the Anesthetic Plan?

TEE is arranged to be available for the case. After an appropriate fasting interval, the patient is transferred to the operating room with inhaled prostacyclin (10 ng/kg/min) and oxygen. A baseline ABG is drawn and shows pH of 7.38, PaCO2 44, PaO2 65, and HCO3 28. Baseline vital signs are sinus tachycardia 103, PAP 65/37, BP 98/62, and 96% on FiO2 40%. An epidural is placed and tested at T5/6. An epidural infusion of bupivacaine and hydromorphone is started. Preoxygenation continues without interruption of the inhaled prostacyclin, and norepinephrine is started at 0.05 mcg/kg/min. After ensuring the surgeons are in the room, induction medications are titrated to effect and include midazolam 2 mg, fentanyl 250 mcg, and ketamine 50 mg. Rocuronium 50 mg is given to facilitate endotracheal intubation. A 37F left-sided double-lumen tube is placed without difficulty, and anesthesia is maintained with sevoflurane and 100% oxygen. Inhaled prostacyclin is continued via the anesthetic circuit. Vital signs are stable with assumption of positive pressure ventilation. The patient is turned to the lateral position and surgery is started. After commencement of OLV, the patient’s PAP climbs to 80/45, BP decreases to 78/40, and ST depression occurs in lead II on ECG. Oxygen saturation drops to 87% on 100%. Pre-existing right ventricular hypokinesis and dilation are seen to worsen on TEE. A temporizing bolus of phenylephrine 200 mcg is given, while the norepinephrine is titrated up to 0.1 mcg/kg/min. A bolus of 250 cc of normal saline is administered, keeping in mind the delicate balance between overloading a failing right ventricle and maintenance of adequate preload to ensure systemic cardiac output. Inhaled prostacyclin is titrated up to 30 ng/kg/min. Vital signs move back toward baseline. The surgery is completed, the patient is extubated, awake, and comfortable. Norepinephrine is titrated off in recovery, and the prostacyclin is titrated down to baseline. The patient returns back to intensive care for close observation.

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Reimer, C., Granton, J. (2019). Pharmacology of the Pulmonary Circulation. In: Slinger, P. (eds) Principles and Practice of Anesthesia for Thoracic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-00859-8_9

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