Inhaled NO in PPHN: Dose Responses and Acute Withdrawal in Newborns with Pulmonary Artery Pressure Monitoring

Abstract 1908 Clinical Trials in Perinatal Neonatal Medicine Platform, Tuesday, 5/4

Introduction: Inhaled nitric oxide (iNO) improves oxygenation in newborns with persistent pulmonary hypertension (PPHN). Conversely, acute withdrawal of iNO may result in an acute decrease in oxygenation. Although animal and human studies demonstrate that iNO produces selective, dose-dependent pulmonary vasodilation, and that acute withdrawal of iNO produces pulmonary vasoconstriction, the pulmonary vasoactive effects of iNO in newborns with PPHN have not been studied. In addition, the mechanism of the changes in oxygenation and the optimal dosing regimen of iNO in these patients are unknown. The objectives of this study were (1) to determine if iNO produces dose-dependent pulmonary vasodilation in newborns with PPHN; (2) to characterize the pulmonary vasoactive response to acute withdrawal of iNO; and (3) to correlate these vasoactive effects with changes in oxygenation.

Methods: Seven newborns with hypoxemia (post-ductal PaO₂<75 torr) and echocardiographic evidence of pulmonary hypertension despite mechanical hyperventilation with an FiO₂ of 1.0 were studied. 5 Fr. balloon-tipped end-hole catheters were placed into the pulmonary artery, via the femoral vein, under echo guidance. During continuous pulmonary and systemic arterial pressure monitoring, 3 doses of iNO (5, 20, and 40 ppm) were administered in random order for 20 minutes each. The hemodynamic variables (systemic and pulmonary arterial pressures) and systemic arterial blood gases and pH were measured at each new steady-state. In 2 of these newborns, iNO (10 ppm) was acutely withdrawn after 24 hours of therapy, and the hemodynamic variables were again determined.

Results: iNO produced dose-dependent (0-20 ppm) decreases in mean pulmonary artery pressure (PAP); 40 ppm did not further decrease PAP. Changes in diastolic pulmonary artery pressure paralleled these changes in mean pressure. Systemic arterial pressure was unchanged. iNO also produced dose-independent increases in post-ductal PaO₂ (See Table). The increase in post-ductal PaO₂ correlated with the decrease in the pulmonary-to-systemic arterial pressure ratio (PAP/SAP)(P<0.05). Acute withdrawal of iNO induced a rapid, reversible increase in the PAP/SAP (from 0.57±0.08 to 1.1±0.04) and decrease in PaO₂ (from 56.0±7.0 to 30.0±9.8 torr)(n=2). Values are mean±S.D. N=7, *P<0.05 vs. previous column (ANOVA).

Table 1 No caption available

Conclusion: This is the first demonstration that iNO produces selective pulmonary vasodilation in newborns with PPHN, and that acute withdrawal of iNO produces pulmonary vasoconstriction. In addition, these data suggest that the changes in oxygenation are secondary to iNO's pulmonary vasoactive effects. Although the improvement in oxygenation is dose-independent, these data suggest that 20 ppm iNO provides maximal pulmonary vasodialation, and should be considered as an initial therapeutic dose.