Inhaled
nitric oxide (iNO) has been shown to improve oxygenation in severe persistent
pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various
lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute
respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO
therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or
acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and
sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory
shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with
meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with
congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required
extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO
therapy, a gestational age > or =34 weeks, and associated diagnosis other than
congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic
respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited
barotrauma using exogenous
surfactant and HFOV may obviate the need for
extracorporeal membrane oxygenation in many term infants.