Inhaled NO and Sildenafil Combination in Cardiac Surgery Patients With Out-of-Proportion Pulmonary Hypertension

Abstract

Background-The goal of this study was to examine the effects of coadministration of sildenafil and inhaled nitric oxide (iNO) in patients with out-of-proportion pulmonary hypertension who underwent cardiac valve replacement surgery. Methods and Results-Twenty consecutive cardiac surgery patients with out-of-proportion pulmonary hypertension were randomly assigned postoperatively into 2 groups: group A received 10 ppm of iNO followed by sildenafil (100 mg) orally 30 minutes later, and group B initially received sildenafil (100 mg) orally followed by 10 ppm of iNO 60 minutes later. Hemodynamic and gas exchange data were obtained at baseline, after administration of either iNO or sildenafil alone, and at 90 minutes from baseline. In group A, iNO resulted in a significant reduction in mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) (by 9.6% and 20.8%, respectively). In group B, sildenafil administration also resulted in a significant decrease in mean arterial pressure, MPAP, pulmonary artery occlusive pressure, PVRI, and systemic vascular resistance index but also in the PaO 2 /inspired fraction of oxygen ratio (by 18.7%, 22.0%, 15.7%, 31.6%, 21.3%, and 14%, respectively). In both groups, the coadministration of the 2 drugs resulted in a significant further reduction of mean arterial pressure, MPAP, pulmonary artery occlusive pressure, systemic vascular resistance index, and PVRI, whereas cardiac index and mixed venous oxygen saturation remained unchanged. The hypoxemia after sildenafil administration in group B improved after the coadministration of iNO, and thus PaO 2 /inspired fraction of oxygen returned to values near baseline. Conclusion-In this study, the postoperative coadministration of iNO and oral sildenafil in patients with out-of-proportion pulmonary hypertension undergoing cardiac surgery is safe and results in an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch. (Circ Heart Fail. 2012;5:47-53.)

Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

“…In these pulmonary hypertensive animals, we have previously shown that PVR is elevated (7,18) and PDE5 activity is increased (18). Yet, there is animal (27) and clinical (12) evidence that the sildenafil and inhaled NO combination results in greater pulmonary vasodilation compared with the use of either agent individually. Sildenafil has been recently shown to have a positive inotropic effect on cardiomyocytes (24), possibly explaining its additive therapeutic beneficial effect independent from its pulmonary vasodilator activity.…”

Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

“…These continue to demonstrate biological benefits, hemodynamically important physiological benefit and have begun to demonstrate some meaningful clinical outcomes such as reduction in duration of mechanical ventilation and stay in the intensive care unit (74)(75)(76)(77)(78)(79)(80). However, these studies remain to involve only a limited surgical patient population, have not progressed beyond single institutional boundaries and lack any demonstration of survival benefit.…”

Nadciśnienie płucne w przebiegu chorób lewego serca — aktualne leczenie i kierunki rozwoju terapii

“…W przypadku chorych po transplantacji serca leczenie inhalacjami NO indukowało selektywne zmniejszenie PVR bez wpływu na opór systemowy [32]. W nowszych badaniach stwierdzono, że łączne zastosowanie w okresie pooperacyjnym u chorych z PH po operacjach kardiochirurgicznych inhalacji NO i doustnego podawania sildenafilu było bezpieczne i wiązało się z obniżeniem PAP i PVR bez systemowej hipotonii i zaburzeń stosunku wentylacji do perfuzji [33].…”