OBJECTIVE: Hypoxemic respiratory failure in the newborn infant due to severe parenchymal lung disease is caused by large, intrapulmonary, right-to-left shunting. Nitric oxide (NO) has been shown to reduce shunting and improve oxygenation-however inconsistently-in a variety of neonatal lung diseases such as meconium aspiration pneumonitis, bacterial pneumonia, surfactant deficiency, and others. The aim of this study was to determine whether lung expansion, as determined by functional residual capacity (FRC), by means of increasing levels for positive end-expiratory pressure (PEEP) would augment the effect of NO on reducing right-to-left shunting. DESIGN: Prospective, randomized, controlled, animal laboratory investigation. SETTING: University laboratory. SUBJECTS: Newborn piglets (n = 8), anesthetized and mechanically ventilated. INTERVENTIONS: The piglets were made surfactant deficient by repeated airway lavage aiming at a Pao(2) of 45 mm Hg (6 kPa) while using an Fio(2) of.6. Two hours after lavage, different PEEP levels of 4, 6, 8, 10, and 12 cm H(2)O (.4,.6,.8, 1.0, and 1.2 kPa) were used in a random order, keeping tidal volumes strictly at 8 mL/kg. All measurements were made with or without NO at 10 ppm in a random order, thus each animal served as its own control. A nitrogen washout method was used to measure FRC and alveolar volume, in addition to tidal volume, and compliance and resistance of the respiratory system. MEASUREMENTS AND MAIN RESULTS: Improvement in oxygenation and reduction of right-to-left shunting was optimal while achieving FRC values comparable with those values before airway lavage (approximately 25 mL/kg) while using PEEP levels of 6 to 8 cm H(2)O (.6 to.8 kPa). Further lung expansion did not augment the NO effect. In addition, alveolar volume and compliance of the respiratory system were positively influenced by NO, resulting in a small, but significant, decrease in Paco(2). CONCLUSION: We conclude that improvement in oxygenation by the administration of inhaled NO can be optimized by achieving FRC values comparable with those of the undiseased lung before airway lavage.

In a 7-month-old infant with bronchopulmonary dysplasia and respiratory syncytial virus (RSV) pneumonia, we have shown an additive effect of high-frequency ventilation (HFV) and inhaled nitric oxide (iNO) in terms of improved oxygenation and the avoidance of extracorporeal membrane oxygenation. Apparently, the combined therapy of HFV and iNO is superior to either therapeutic modality alone in the treatment of hypoxemic respiratory failure due to RSV pneumonia. The mechanism of increased lung expansion and alveolar recruitment appears to be responsible for a favorable clinical outcome. We conclude that the combined therapy of HFV and iNO should be considered in hypoxemic respiratory failure in pediatric patients.

Synergistic Effect of High-Frequency Ventilation (HFV) and Inhaled Nitric Oxide (iNO) in the Treatment of Neonatal Hypoxemic Pulmonary Failure 1670

ANTIMICROBIAL ACTIVITY OF NITRIC OXIDE (NO) IN CONCENTRATIONS USED DURING INHALATIVE NO THERAPY 1993