Comparative Effects of Brief Inhaled Milrinone Versus Intravenous Milrinone on Pulmonary Arterial Pressure in Patients Undergoing Mitral Valve Surgery

Perioperative pulmonary hypertension (PHT), an independent risk factor for cardiac surgery, 1,2 is frequently associated with chronic mitral valve regurgitation and tends to produce right ventricular (RV) dysfunction. Worsening PHT, which is sensitive to any increase in the RV afterload, reduces the right coronary perfusion pressure, exacerbates RV dysfunction, and compromise the left ventricular (LV) preload and systemic perfusion pressure. 3,4 Although intravenous (IV) milrinone is preferred for treating PHT due to its beneficial effects in enhancing myocardial contractability without increasing the heart rate-related myocardial oxygen consumption, 5-7 its frequent association with systemic vasodilation requires additional vasoconstrictor therapy for maintaining the optimal perfusion pressure.8-10 Selective pulmonary vasodilation, which reduces the RV afterload without systemic arterial vasodilation, is important for managing PHT and the accompanying RV dysfunction.11 A study reported that nebulized and inhaled (IH) milrinone ( 1 mg/ml) produced dose-dependent selective pulmonary vasodilatation in postoperative PHT in the intensive care unit.12 If IH milrinone during the pre-cardiopulmonary bypass (CPB) period produces selective pulmonary vasodilation in patients with PHT undergoing mitral valve surgery, it would be a beneficial option for managing intraoperative PHT.

Our main hypothesis is that a brief inhaled milrinone could reduce the pulmonary arterial pressure without the systemic side effects better than intravenous milrinone in elevated pulmonary artery pressure patients. The aim of this study is to determine the effects of hemodynamic before and after administering IH and to compare them to those of IV milrinone in patients with elevated pulmonary artery pressure due to severe mitral regurgitation undergoing mitral valve surgery.

Materials and Methods Experimental Groups Adult patients with PHT (systolic PAP > 50 mmHg estimated by the velocity of tricuspid valve regurgitation in preoperative transthoracic echocardiography) undergoing mitral valve surgery for chronic mitral regurgitation are enrolled in this study after obtaining approval from the institutional research board and providing written informed consent.

Preoperative exclusion criteria include preoperative supraventricular tachycardia (SVT), atrial fibrillation, atrial flutter, multiple ventricular ectopic contractions, continuous inotropic support, LV ejection fraction (EF) < 30%, emergent surgery, obstructive cardiomyopathy, bleeding diatheses, bronchial asthma and had biochemical evidence of hepatic disease or renal impairment.

The pharmacist implements the randomization process for grouping the patients by giving the enrolled patients, a patient identification number (PIN). Then, the patients are stratified by their PIN in a 1:1 ratio to receive IH (Primacor, Sanofi-Synthelabo Canada Inc., Markham, ON, Canada) (Group IH) or IV (Group IV) milrinone. The investigators are blinded to the allocation of the study group.