INHALED NITRIC OXIDE GAS IMPROVES OXYGENATION IN PPHN. • 1430

Pilot studies suggest that inhaled NO (iNO) is a selective, pulmonary vasodilator that increases systemic oxygenation in newborns with persistent pulmonary hypertension (PPHN). We undertook a masked, prospective, randomized, multicenter study to examine whether iNO increases or stabilizes systemic oxygenation in patients with severe PPHN in comparison with conventional ventilation therapy. Full term infants with PPHN mechanically ventilated at FiO₂ 1.0 with a postductal PaO₂ ≤ 55 mmHg were randomized to breathe either 0 or 80 parts per million (ppm) NO at FiO₂ 0.90 via a pressure-limited, time-cycled ventilator. Infants with systemic hypotension, structural cardiac disease, lung hypoplasia/diaphragmatic hernia, lethal congenital abnormalities, or previous treatment with high frequency oscillatory/jet ventilation or exogenous surfactant were excluded from the study. Treatment was deemed `successful' if it decreased the oxygen index to< 40, and did not decrease PaO₂ < 15% or cause systemic hypotension. For patients whose study gas was not successful, alternate treatments, including ECMO, could be utilized; in those whose therapy was successful, the therapeutic gas concentration was progressively decreased.

Fifty patients were studied over three years. No difference was observed in the initial PaO₂, ventilator support, gestational age, birth weight, or gender between the treatment groups. During the reduction of FiO₂ from 1.0 to 0.9 prior to initiation of the treatment gas, no significant decrease in postductal PaO₂ or systemic blood pressure was measured. Treatment with iNO was successful in 14 / 25 (56%) babies, but conventional ventilator therapy was successful in only 3 / 25 (6%). iNO increased the probability of success nearly 20-fold (balanced odds ratio, p<0.05). In control patients, postductal PaO₂ was 45±6 mmHg (M±SE), Whereas iNOtreatment caused a PaO₂ of 88±15 mmHg, the 14 infants successfully treated with iNO had a PaO₂ of 124±22 mmHg. No patient exhibited systemic hypotension during treatment with iNO. Our study demonstrates that inhaled NO markedly improves the systemic oxygenation of infants with PPHN. Additional studies examining the optimal iNO-treatment concentration and its effect on outcome should be performed.