Use of Combination of Nitric Oxide and Sildenafil in the Management of Severe Pulmonary Hypertension in Mitral Valve Replacement: A Case Report

Dear Editor, We would like to share a case illustrating the perioperative management of severe pulmonary hypertension (PH) in cardiac surgery, emphasizing the critical role of advanced hemodynamic monitoring, selective pulmonary vasodilators, and a multimodal inotropic strategy. PH is a complex hemodynamic condition characterized by elevated mean pulmonary arterial pressure (mPAP) above 20 mmHg, which can result from various etiologies, including pulmonary arterial hypertension and left heart disease-related PH.[1,2] Its pathophysiology involves vasoconstriction, endothelial dysfunction, vascular remodeling, and increased pulmonary vascular resistance (PVR), ultimately leading to right ventricular failure.[3,4] We report the case of a 35-year-old woman with rheumatic mitral stenosis and mixed PH who presented with progressive dyspnea and worsening hemodynamics. Echocardiography revealed a dilated right ventricle with an end-diastolic volume of 50 mm3 and hypocontractility with a fractional area change (FAC) of 30%, as well as an enlarged left atrium with a volume of 47 mm3. The mitral valve had a valve area of 0.4 cm² and a mean gradient of 26 mmHg. There was significant commissural asymmetry with extensive thickening of the posteromedial commissure, resulting in an eccentric orifice. The transpulmonary pressure was calculated by right heart catheterization performed before the surgical procedure. The systolic pulmonary artery pressure was 108 mmHg. A manometric examination during a previous cardiac catheterization revealed an aortic pressure of 89/58 (69) mmHg, while the transpulmonary pressure gradient was 77/42 (57) mmHg. The right atrium pressure was 8 mmHg, and the mean value transmitral gradient was 21 mmHg. The cardiac index was 0.85l/min/m2, and PVR was 13.42 mmHg L-1 min, while systemic vascular resistance (SVR) was 38.98 Woods. The patient underwent mitral valve replacement with a perioperative strategy aimed at optimizing right ventricular function and minimizing PH-associated complications. The anesthetic induction included etomidate, ketamine, and nitric oxide (NO) at 20 ppm, combined with a bilateral parasternal block for opioid-sparing analgesia. Inhaled nitric oxide (iNO) was continuously administered prebypass, with an eventual increase to 40 ppm, yielding partial reductions in pulmonary pressures. Cardiopulmonary bypass (CPB) lasted 76 minutes, with an aortic cross-clamp time of 64 minutes. Before weaning from CPB, 50 mg of sildenafil was administered. Postoperatively, a multimodal inotropic regimen of dobutamine, milrinone, and vasopressin was initiated, ensuring hemodynamic stability. The patient was extubated on the same day and discharged from the ICU 3 days later. The patient was transferred to the ICU on 40 ppm of inhaled nitric oxide (iNO) and underwent weaning following the department’s protocol. The weaning process involved gradual reductions of 10 ppm at a minimum interval of 2 hours, with continuous monitoring of hemodynamic parameters to assess tolerance. The patient tolerated all dose reductions well, and there was no need to delay extubation. PH management in cardiac surgery remains challenging, particularly in patients with mixed etiology. Pulmonary artery catheterization was essential in guiding hemodynamic interventions.[5] During the preoperative management, right heart catheterization was performed to assess the pressures which the results showed PVR of 38 mmHg L-1 min and a pulmonary arterial wedge pressure of 36 mmHg L-1 min, indicating hypertension with both precapillary and postcapillary characteristics. Furthermore, when analyzing the transpulmonary gradient (TPG of 21 mmHg) and the diastolic transpulmonary gradient (DPG of 6 mmHg), the data reinforce the conclusion of “out of proportion” pulmonary hypertension. iNO, although primarily studied in pediatric populations, has demonstrated efficacy in reducing PVR and facilitating CPB weaning in adult cardiac surgery patients.[6] Its role in improving ventilation-perfusion matching, reducing intrapulmonary shunting, and exerting protective endothelial effects makes it a valuable perioperative adjunct.[7] Despite its established clinical role, iNO’s optimal dosing and timing remain subjects of debate. Studies suggest no added benefits with higher doses, and its prophylactic versus reactive use is yet to be clarified.[8,9] The combination of iNO with sildenafil, a phosphodiesterase type 5 inhibitor, provided synergistic effects, allowing successful weaning from intravenous pulmonary vasodilators. Although sildenafil is widely used in chronic PH, its intraoperative administration in cardiac surgery remains less explored. Shim et al. demonstrated that preoperative sildenafil induces significant pulmonary vasodilation without systemic hypotension.[10,11] In our case, sildenafil was administered 40 minutes before CPB weaning based on its pharmacokinetics, contributing to smooth postoperative recovery. The duration of CPB and the hemodynamic monitoring at the time were assessed, and it was determined that the risk of right ventricular failure would be more significant than the risk of vasoplegia. In addition, it was believed that the vasodilatory effects of sildenafil would not be significant enough to compromise hemodynamic management. A multimodal inotropic strategy was used, with milrinone and dobutamine enhancing myocardial contractility through complementary mechanisms. Meissner et al. showed that their combined use resulted in improved stroke volume index and reduced pulmonary capillary wedge pressure without significant systemic effects.[12,13] It was necessary to start a vasopressor to correct the drop in SVR, and vasopressin was chosen due to its lack of effect on the pulmonary vasculature. In conclusion, the successful perioperative management of this complex case highlights the importance of individualized therapeutic strategies, including advanced hemodynamic monitoring, selective pulmonary vasodilators, and a multimodal approach to inotropic support. The synergistic use of iNO and sildenafil, with careful timing and dosing, proved effective in optimizing pulmonary vascular resistance and facilitating recovery. This case underscores the necessity of a multidisciplinary approach in addressing the challenges of PH in cardiac surgery. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.