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EDITORIAL Table of Contents   
Year : 2010  |  Volume : 13  |  Issue : 2  |  Page : 89-91
Perioperative management of pulmonary hypertension

Department of Anaesthesiology and Intensive Care, G.B. Pant Hospital, New Delhi-110 002, India

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Date of Web Publication3-May-2010

How to cite this article:
Tempe DK. Perioperative management of pulmonary hypertension. Ann Card Anaesth 2010;13:89-91

How to cite this URL:
Tempe DK. Perioperative management of pulmonary hypertension. Ann Card Anaesth [serial online] 2010 [cited 2022 Nov 29];13:89-91. Available from:

The presence of pulmonary arterial hypertension (PAH) is a significant predictor of major perioperative cardiovascular complications in patients undergoing cardiac or noncardiac surgery. The PAH is commonly considered to exist when the mean pulmonary artery pressure (PAP) exceeds 25 mm Hg at rest and 30 mm Hg during exercise. [1] However, systolic PAP of 50% of the systemic arterial pressure and above is not uncommon and occasionally, the PAP can be systemic or even suprasystemic in patients suffering from cardiac disease. The risk of pulmonary hypertensive crisis in such patients is substantial and can increase the morbidity and mortality. One recent report has shown that PAH etiology in children was 56% idiopathic (primary), 21% congenital heart disease, 14% chronic lung disease, 4% chronic airway obstruction, and 4% chronic liver disease. [2] In addition, PAH remains a major problem during the perioperative period for adults with congenital heart disease, long-standing valvular heart disease, [3] and those undergoing cardiac transplantation. [4]

Although the surgical correction of a congenital defect or valvular heart disease often leads to substantial decrease in the PAP, careful and stringent perioperative management of PAH during the entire perioperative period is crucial for improving the outcome in these patients. The cardiac anesthesiologist assumes an important role in the management of such patients. The basic objective is to control the PAP and prevent the episodes of pulmonary hypertensive crisis, so that the risk of right ventricular dysfunction / failure is decreased.

Over the years there have been multiple classes of drugs developed for the treatment of PAH. Nitroglycerin and sodium nitroprusside are the oldest pulmonary vasodilators used in the operating room. Later on phosphodiesterase (PDE) inhibitors were introduced. Milrinone, a PDE-3 inhibitor is one of the most commonly used agents in this class in the operating room, and sildenafil, a specific PDE-5 inhibitor has been shown to be highly effective in the management of pulmonary hypertension.

Prostaglandins are potent endogenous vasodilators that mediate the action via increases in the cyclic AMP in the vascular smooth muscle. They have an additional therapeutic effect in the form of remodeling of the pulmonary vascular bed with subsequent reduction of endothelial cell injury and hypercoagulability. [5] Among epoprostenol and iloprost, the latter is more potent and has a half life greater than 13 minutes.

Among the newer lot, levosimendan, an inotrope which is a calcium 'sensitizer' has been shown to decrease the pulmonary capillary wedge pressure, systemic vascular resistance (SVR), and PAP in patients with moderate-to-severe congestive heart failure. [6] Adenosine infusion at a dose of 50 ΅g/kg/min can produce a substantial decrease in pulmonary vascular resistance (PVR) and an increase in cardiac output without adversely affecting the systemic hemodynamics. [7] Bosentan, an orally active endothelin antagonist has significantly changed the therapeutic approach to PAH. [8] Brain natriuretic peptide secreted by the ventricles of the heart cause an increased intracellular concentration of guanosine 3'5'-cyclic monophosphate (cGMP), and smooth muscle cell relaxation. It is currently the most selective and efficient intravenous pulmonary vasodilator without any significant systemic effects and is being increasingly used during cardiac surgery. [4]

All the intravenous agents suffer from the disadvantage of systemic vasodilatation leading to hypotension, necessitating the concomitant use of vasopressors with their inherent drawbacks. Therefore, an agent having selective vasodilatory action on the pulmonary vasculature is desirable. In this respect, inhaled nitric oxide has long been the 'gold standard' of inhaled pulmonary vasodilators, and is the standard agent with which the other inhaled agents are compared. Nitric oxide activates the enzyme guanylate cyclase. Activated guanylate cyclase produces cGMP, which then leads to vasodilatation. The vasodilatation in the areas of the lung that are better ventilated leads to redistribution of pulmonary blood flow away from lung regions, with low ventilation / perfusion ratios toward regions with normal ratios. [9] The systemic exposure is limited by rapid inactivation in blood cells, the half life of nitric oxide is only a few seconds. Nitric oxide is administered in the dose of 5 - 40 parts per million via the inspiratory limb of the breathing circuit. The efficacy and safety of nitric oxide in the cardiac operating room has been extensively documented. [10],[11] Nevertheless, nitric oxide suffers from the disadvantage of rebound PAH and right ventricular failure on discontinuation, risk of methemoglobinemia, and toxicity of nitrogen dioxide. In addition, cost of nitric oxide as well as the equipment required for accurate monitoring of both nitric oxide and nitrogen dioxide is a consideration.

Consequently, inhalation of all other vasodilators, such as sodium nitroprusside, [12],[13] nitroglycerin, [14] PDE inhibitors, [15] as well as, prostaglandins [16] has been tried. Among these, milrinone and prostaglandins deserve mention. The concept of using inhaled milrinone is not new. Haraldsson, et al., in 2001, have demonstrated that inhaled milrinone causes selective pulmonary vasodilatation in cardiac surgical patients with postoperative pulmonary hypertension. [16] More recently, in a report of 18 heart transplant recipients, inhaled milrinone has been shown to decrease mean PAP, transpulmonary gradient, and PVR. [17] No systemic side effects were seen with a dose of 2 mg inhaled through a nebulizer. It seems that inhaled milrinone presents a novel method of therapy for PAH. It is cheaper and less cumbersome to administer as compared with nitric oxide and it can be administered prior to the institution of cardiopulmonary bypass (CPB) in patients with severe PAH, where it could prevent the post-bypass reperfusion injury associated with severe PAH. [18]

Inhaled prostaglandin I 2 (PGI 2 ) offers similar advantages. The first reported use of inhaled PGI 2 was described in 1978. [19] It has emerged as a ready alternative to inhaled nitric oxide and has been shown to be equivalent to inhaled nitric oxide in the treatment of PAH. [20] In addition, a synergistic effect is seen when nitric oxide and PGI 2 are administered together. [21] Inhaled PGI 2 suffers from the theoretical disadvantage of bleeding (due to platelet inhibition) and rebound PAH with abrupt discontinuation. A possible alternative is iloprost, which is a stable derivative of PGI 2 . It has similar vasodilator properties and a longer half life of 30 minutes. [22] It has been seen to be effective as a rescue therapy for pulmonary hypertensive crisis in children undergoing congenital heart surgery. [23] Prostaglandin E1 is another potential alternative via the inhaled route, but there is lack of published data with this prostaglandin. [24]

In this issue of the Annals of Cardiac Anaesthesia, Mandal and colleagues present the hemodynamic effects of nitroglycerin (inhaled and intravenous) with and without dobutamine infusion. [25] Such an effort seems to be related to the fact that some of the newer pulmonary vasodilators are not readily available in India. They have shown that only inhaled nitroglycerin has selective pulmonary vasodilatory effect (decrease in PAP, PVR and PVR/SVR ratio). Addition of dobutamine to inhaled nitroglycerin did not decrease the SVR, but it did not affect the PVR/SVR ratio. Intravenous nitroglycerin (with and without dobutamine) had significant systemic vasodilatory effect.

It is clear that several newer options are now available for the management of perioperative PAH and right ventricular failure. However, the anesthesiologist must not ignore the basic principles of anesthesia and must avoid hypoxia, hypercarbia, acidosis, and hypothermia, which can lead to pulmonary vasoconstriction. In addition, careful airway manipulations and pain management are of paramount importance. This must be the first step of the overall treatment strategy. The next step should be the use of appropriate inotropes such as dobutamine, epinephrine, and PDE3 inhibitors. The selective pulmonary vasodilators should then be used. Based on the availability, inhaled agents may often be the first line of therapy. More often than not, a multimodal approach is more rewarding than using a single therapeutic agent. Despite the best therapeutic measures, there will be non-responders. The treatment of this subset is challenging and several novel methods have been used in such a scenario. These include nebulized milrinone, [26] oral sildenafil, [27],[28],[29] magnesium, [30] and even oral nifedipine. [31] In addition, adjunctive therapy with natriuretric peptide or bosentan can be utilized. In summary, the current advances in the therapy of PAH provide a wide choice and the morbidity and mortality associated with PAH is bound to decrease in the days to come.

   References Top

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2.Carmosino MJ, Friesen RH, Doran A, Ivy DD. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007;104:521-7.  Back to cited text no. 2      
3.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;132:1420-5.  Back to cited text no. 3      
4.Ramakrishna H. Advances in the perioperative management of pulmonary hypertension. Front Cardiovasc Drug Discov 2010;1:1-17.  Back to cited text no. 4      
5.Friedman R, Mears JG, Barst RJ. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation 1997;96:2782-84.  Back to cited text no. 5      
6.Nieminen MS, Akkila J, Hasenfuss G, Kleber FX, Lehtonen LA, Mitrovic V, et al. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 2000;36:1903-12.  Back to cited text no. 6      
7.Fullerton DA, Jones SD, Grover FL, McIntyre RC Jr. Adenosine effectively controls pulmonary hypertension after cardiac operations. Ann Thorac Surg 1996;61:1118-23.  Back to cited text no. 7      
8.Raja SG, Dreyfus GD. Current status of bosentan for treatment of pulmonary hypertension. Ann Card Anaesth 2008;11:6-14.  Back to cited text no. 8  [PUBMED]  Medknow Journal  
9.Steudel W, Hurford WE, Zapol WM. Inhaled nitric oxide: basic biology and clinical applications. Anesthesiology 1999;91:1090-121.  Back to cited text no. 9      
10.Blaise G, Langleben D, Hubert B. Pulmonary arterial hypertension: pathophysiology and anesthetic approach. Anesthesiology 2003;99:1415-32.  Back to cited text no. 10      
11.Ichinose F, Roberts JD Jr, Zapol WM. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation 2004;109:3106-11.  Back to cited text no. 11      
12.Schόtte H, Grimminger F, Otterbein J, Spriestersbach R, Mayer K, Walmrath D, et al. Efficiency of aerosolized nitric oxide donor drugs to achieve sustained pulmonary vasodilation. J Pharmacol Exp Ther 1997;282:985-94.  Back to cited text no. 12      
13.Meadow W, Rudinsky B, Bell A, Hipps R. Effects of nebulized nitroprusside on pulmonary and systemic hemodynamics during pulmonary hypertension in piglets. Pediatr Res 1998;44:181-6.  Back to cited text no. 13      
14.Gong F, Shiraishi H, Kikuchi Y, Hoshina M, Ichihashi K, Sato Y, et al. Inhalation of nebulized nitroglycerin in dogs with experimental pulmonary hypertension induced by U46619. Pediatr Int 2000;42:255-8.  Back to cited text no. 14      
15.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;93:1439-45.  Back to cited text no. 15      
16.Shimokawa H, Flavahan NA, Lorenz RR, Vanhoutte PM. Prostacyclin releases endothelium-derived relaxing factor and potentiates its action in coronary arteries of the pig. Br J Pharmacol 1988;95:1197-203.  Back to cited text no. 16      
17.Sablotzki A, Starzmann W, Scheubel R, Grond S, Czeslick EG. Selectie pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates. Can J Anaesth 2005;52:1076-82.  Back to cited text no. 17      
18.Denault AY, Lamarche Y, Couture P, Haddad F, Lambert J, Tardif JC, et al. Inhaled milrinone: a new alternative in cardiac surgery? Semin Cardiothorac Vasc Anesth 2006;10:346-60.  Back to cited text no. 18      
19.Szezeklik A, Gryglewski R, Nizankowska E, Nizankowski R, Musial J. Pulmonary and anti-platelet effects of intravenous and inhaled prostacyclin in man. Prostaglandins 1978;16:651-60.  Back to cited text no. 19      
20.Mikhail G, Gibbs J, Richardson M, Wright G, Khaghani A, Banner N, et al. An evaluation of nebulized prostacyclin in patients with primary and secondary pulmonary hypertension. Eur Heart J 1997;18:1499-504.  Back to cited text no. 20      
21.Hill LL, Pearl RG. Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension. J Appl Physiol 1999;86:1160-4.  Back to cited text no. 21      
22.Grant SM, Goa KL. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. Drugs 1992;43:889-924.   Back to cited text no. 22      
23.Limsuwan A, Wanitkul S, Khosithset A, Attanavanich S, Samankatiwat P. Aerosolized iloprost for postoperative pulmonary hypertensive crisis in children with congenital heart disease. Int J Cardiol 2008;129:333-8.  Back to cited text no. 23      
24.van Heerden PV, Barden A, Michalopoulos N, Bulsara MK, Roberts BL. Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS. Chest 2000;117:819-27.  Back to cited text no. 24      
25.Mandal B, Kapoor PM, Chowdhury U, Kiran U, Choudhury M, Acute hemodynamic effects of inhaled nitroglycerine, intravenous nitroglycerine and combinationwith intravenous dobutamine in patients with secondary pulmonary hypertension. Ann Card Anaesth 2010;13:138-44.  Back to cited text no. 25      
26.Buckley MS, Feldman JP. Nebulized milrinone use in a pulmonary hypertensive crisis. Pharmacotherapy 2007;27:1763-6.  Back to cited text no. 26      
27.Peiravian F, Amirghofran AA, Borzouee M, Ajami GH, Sabri MR, Kolaee S. Oral sildenafil to control pulmonary hypertension after congenital heart surgery. Asian Cardiovasc Thorac Ann 2007;15:113-7.  Back to cited text no. 27      
28.Kulkarni A, Singh TP, Sarnaik A, Walters HL, Delius R. Sildenafil for pulmonary hypertension after heart transplantation. J Heart Lung Transplant 2004;23:1441-4.  Back to cited text no. 28      
29.Nemoto S, Umehara E, Ikeda T, Doi T, Hiraumi Y, Yokoyama S, et al. Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery. Kyobu Geka 2004;57:842-5.  Back to cited text no. 29      
30.Lin SC, Teng RJ, Wang JK. Management of severe pulmonary hypertension in an infant with obstructed total anomalous pulmonary venous return using magnesium sulfate. Int J Cardiol 1996;56:131-5.  Back to cited text no. 30      
31.Shyamkrishnan KG, Waikar HD, Titus T. Management of severe pulmonary hypertension during surgery for congenital heart disease. Indian Heart J 1996;48:159-60.  Back to cited text no. 31      

Correspondence Address:
Deepak K Tempe
Department of Anaesthesiology and Intensive Care, G.B. Pant Hospital, New Delhi-110 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9784.62926

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