Nitric Oxide and Milrinone: Combined Effect on Pulmonary Circulation After Fontan-Type Procedure: A Prospective, Randomized Study

Abstract

Early morbidity and mortality after Fontan operations are related to the elevation of postoperative pulmonary vascular resistance. Inhalation of nitric oxide (iNO) and intravenous milrinone are two options capable of reducing pulmonary vascular resistance. We hypothesized that their combined use could maximally stabilize the pulmonary circulation after Fontan operation. Forty-six patients with high pulmonary vascular resistance (transpulmonary pressure gradient >10 mm Hg or central venous pressure >15 mm Hg) and impaired oxygenation after Fontan operation were prospectively randomized into three groups: group Mil (n = 15, milrinone at 0.5 microg x kg(-1) x min(-1)), group iNO (n = 15, iNO at <20 ppm), and group iNO + Mil (n = 16, iNO plus Mil). Pulmonary hemodynamic and oxygenation changes were compared among the three groups. Inhalation of nitric oxide with milrinone led to (1) the most significant reduction of pulmonary vascular resistance (transpulmonary pressure gradient from 11.26 +/- 1.40 mm Hg [baseline] to 7.93 +/- 0.90 mm Hg [24-hour use] in group iNO + Mil versus from 11.10 +/- 1.38 to 8.69 +/- 0.86 mm Hg; p = 0.048 in group iNO and from 11.17 +/- 1.41 mm Hg to 9.72 +/- 1.32 mm Hg; p < 0.001 in group Mil); (2) the most significant improvement of arterial blood oxygenation (ratio of arterial oxygen partial pressure to inspired fraction of oxygen from 68.88 +/- 14.09 to 131.25 +/- 15.92 in group iNO + Mil versus from 70.07 +/-14.24 to 120.20 +/- 15.92; p = 0.047 in group iNO and from 72.60 +/- 12.92 to 95.20 +/- 13.49; p < 0.001 in group Mil). Time on mechanical ventilation was shortest in group iNO + Mil (p = 0.043). Combined use of iNO and milrinone optimally stabilized pulmonary hemodynamics after Fontan operation.