Efficacy of Inhaled Nitric Oxide in Neonates with Hypoxic Respiratory Failure and Pulmonary Hypertension: An Analysis of Time to Improvement in Oxygenation in Japanese Pediatric Patients

Introduction: Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator that improves oxygenation in neonates with hypoxic respiratory failure (HRF), and pulmonary hypertension (PH). In Japan, there is an ongoing observational registry of preterm and term neonates with HRF/PH who received treatment with iNO to assess the safety and effectiveness of treatment in everyday clinical practice. This study was designed to determine the time to improvement in oxygenation in neonates receiving iNO in this Japanese registry.

Materials and Methods: Japanese neonates with HRF/PH who received iNO initiated at a concentration of 20 ppm within 7 days after birth beginning February 26, 2010, to October 9, 2012, were eligible for inclusion in this analysis. Safety and effectiveness data were collected at 1, 4, 12, 24, 48, 72, and 96 hours after iNO initiation and every 24 hours thereafter, if necessary, and just prior to iNO discontinuation. Improvement in oxygenation was defined as either a 10% decrease from baseline in oxygenation index (OI) or a 10% increase from baseline in partial pressure of arterial oxygen. Subgroup analyses were conducted based on gestational age (GA) ( < 34 vs. ≥34 weeks), baseline OI (OI ≥15– < 25 vs. OI ≥25–≤40), and direction of shunt at baseline. Data were evaluated for a total of 1,106 neonates ( < 34 weeks GA: n = 431; ≥34 weeks GA: n = 675).

Results: Improvement in OI was observed in 60% of patients (665 out of 1,106), and the rate of improvement was similar based on GA ( < 34 weeks GA: 61%; ≥34 weeks GA: 59%). Overall mean time to improvement was 11.4 hours; mean time to improvement was longer in ≥34 weeks GA versus 1 hour to show improvement in oxygenation. Neonates with higher baseline OI showed the most marked decrease in OI during the first hour of iNO treatment. The mortality rate was higher among patients who received iNO treatment when OI was ≥25 compared with OI ≥15 to  < 25 ([Table 1]).

Conclusion: Treatment with iNO provided acute and sustained improvement in oxygenation in both neonates within 1 hour to demonstrate the response.

Keywords: inhaled nitric oxide, hypoxic respiratory failure, pulmonary hypertension, preterm neonate, oxygenation index, observational registry, Japan

Table 1 Proportions of patients who experienced OI > 40 at any time point or died, stratified by baseline OI