Abstract 1766

The aim of this analysis was to determine if an acute improvement in oxygenation, defined as an increased PaO2 >20 Torr in response to I-NO (responder), predicted outcome for term infants with PPHN. Patients (N=155) were part of the treatment arm of a previously reported, placebo-controlled, double-masked, multicenter clinical trial from 1994 to 1996. Patients received I-NO (0,5,20, or 80 ppm) at a constant dose until failure or success criteria were met. Pretreatment with surfactant and concomitant high frequency ventilation were not permitted. The primary endpoint for the original trial was the development of at least one PPHN major sequelae (death, ECMO, neurologic sequelae, or bronchopulmonary dysplasia). Secondary endpoints were treatment failure criteria (PaO2 <40 Torr for 1/2 hour) or a sustained improvement in oxygenation (baseline corrected, time weighted oxygenation index up to 24 hours - TWOI). At study entry the PaO2 was 64±39 Torr and the OI was 25±10 at 26±18 hrs after birth (mean, SD). Of the 114 patients receiving I-NO, 53 (47%) were classified as acute responders, while 61(53%) were not. There were no statistically significant differences between patients receiving I-NO (pooled doses) classified as responders versus non-responders with respect to the primary endpoint including death and/or ECMO. Treatment failure occurred less frequently for responders versus non-responders (15% versus 36%, p=0.01). The TWOI was lower for responders versus non-responders (-8.4 versus -2.0, p<0.01). There was no difference in response rate for PPHN patients by underlying disease, however the response rate was greater when the baseline OI was <25 versus ≥25 (64% versus 29%, p<0.01). If a higher threshold of PaO2 is used as the definition of an acute responder (> 70 Torr increase, i.e. above the median PaO2 for responders), there is still no statistical difference in outcome compared to non-responders. We conclude that, although acute responders to I-NO (based on a generally utilized definition) have a more sustained improvement in oxygenation and less deterioration to severe hypoxemia, this response is not predictive of outcome and the need for ECMO when early treatment of PPHN is started with I-NO and conventional ventilation. (funded by Ohmeda, PPD)