Oxygenation Improves Sooner with iNO Therapy in PH Newborns, Registry Study Finds

Upon treatment with inhaled nitric oxide, oxygenation improved faster in preterm, near-term, and term newborns with hypoxic respiratory failure and pulmonary hypertension (PH), a Japanese study shows.

The registry-based study, “An Analysis of Time to Improvement in Oxygenation in Japanese Preterm and Late Preterm or Term Neonates with Hypoxic Respiratory Failure and Pulmonary Hypertension,” was published in the journal Clinical Therapeutics.

Inhaled nitric oxide (iNO) can be used to dilate (widen) blood vessels, and reduce pulmonary arterial pressure in newborns with PH.

Studies have shown beneficial effects associated with iNO treatment, namely in improving oxygenation in term and near-term (gestational ages more than 34 weeks) newborn infants. As a result, neonates (newborns) with hypoxic respiratory failure (abnormal oxygen/carbon dioxide exchange in the respiratory system) and PH may be given iNO in combination with oxygen support or disease-relevant treatments.

Based on results showing similar oxygenation progress in preterm (fewer than 34 weeks), near-term, and term newborn groups upon iNO treatment, the Japanese researchers evaluated the time to iNO-associated improvements in newborns with hypoxic respiratory failure and PH.

The study collected registry data from neonates (mean gestational age 34.1 weeks) with hypoxic respiratory failure associated with PH (1,106 patients) receiving iNO in Japan.

Newborns in the study received iNO within seven days after birth, with a starting concentration of 20 parts per million (ppm), which was reduced gradually until discontinuation.

Researchers assessed oxygenation index (inhaled oxygen wherein a lower index indicates clinically better outcomes), and partial oxygen pressure just before iNO administration (at baseline), at various intervals between one hour and 96 hours (four days) after first administration, and just before treatment discontinuation.

Oxygenation improvements were defined as a 10% reduction in oxygenation index, or a 10% increase in the partial pressure of oxygen from baseline. In case the infants required longer than a four-day treatment, researchers collected data every 24 hours.

Compared with baseline, 60% of the newborns experienced improvements in oxygenation, with a mean time to improvement of 11.4 hours from the first iNO administration. This time tended to be shorter in the group below 34 weeks of gestation versus the one with 34 or more weeks — 9.2 versus 12.9 hours.

Data based on gestational age showed similar oxygenation improvements between infants younger than 34 weeks (61%) and those of 34 weeks and older (59%).

Thirty-percent of the infants showing improved oxygenation needed iNO treatment for longer than one hour. These results also were independent of gestational age.

Classification of the data into different levels of oxygenation index at baseline showed significantly higher mortality rates (24.8%) among newborns with the highest oxygenation index levels levels (25 or more). These results contrasted with mortality rates of newborn infants with lower oxygenation index levels — 15 or more, 12.1% mortality rate; and less than 15, 8.9% mortality rate.

Importantly, iNO treatment caused the most marked reduction in oxygenation index within the first hour of therapy among newborns with higher baseline indexes. The oxygenation indexes of these infants continued to decrease with time, even after one day of administration.

“On the basis of the data compiled in the present study, it appears that early initiation of iNO […] and adequate duration of iNO exposure (at least 1 hour) may be associated with clinically meaningful improvements in iNO-treated neonates,” the team concluded.

“These data also suggest that initiation of iNO treatment before oxygenation index reaches 25 is important for improving survival,” the researchers added.