Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity

Abstract

Background: Inhaled nitric oxide (INO) is used to treat hypoxic respiratory failure without clear evidence of benefit. Future trials to evaluate its use will be designed based on an understanding of the populations in which this therapy is provided and with outcomes based on patient characteristics, for example, a history of premature birth.

Methods: This was a multi-center prospective observational study that evaluated subjects in the pediatric ICU who were treated with INO for a respiratory indication, excluding those treated in the neonatal ICU or treated for birth-related disease. We used logistic regression to evaluate characteristics associated with mortality and duration of mechanical ventilation. Specifically, we compared subjects born early preterm (<32 weeks post-conceptual age), late preterm (32-37 weeks post-conceptual age), and full term.

Results: A total of 163 children (median age [interquartile range], 1.8 [0.7-6.0] y) were included, 41 (25.2%) had a history of preterm birth (18 born early preterm and 23 born late preterm). INO was initiated for less-severe lung disease in the early preterm versus late preterm versus full-term subjects (median mean airway pressures, 16 vs 19 vs 19 cm H₂O; P = .03), although the oxygenation index and oxygenation saturation index did not differ. The early preterm subjects had more ventilator-free days (median, 18.0, 7.0, 4.5 d; P = .02) and lower 28-d mortality (0, 26.1, 32.0%; P = .007). Lower respiratory tract disease, but not a history of prematurity, was independently associated with lower mortality.

Conclusions: INO was used differently in early preterm subjects. Clinical trials that evaluate INO use should have standardized oxygenation deficit thresholds for initiation of therapy and should consider stratifying by early preterm status.

Keywords: Acute Respiratory Distress Syndrome; critical care outcomes; infant; nitric oxide; pediatric; premature; pulmonary hypertension; right ventricular failure.

Fig. 1.

Flow chart. *Subjects may have more than one reason for exclusion. INO = inhaled nitric oxide; CDH = congenital diaphragmatic hernia; MAS = meconium aspiration syndrome; PPHN = primary pulmonary hypertension of the newborn.

Fig. 2.

Time to discontinuation of inhaled nitric oxide (INO). Among survivors, there was no difference in the duration of treatment with INO based on prematurity status (log rank test, P = .45).