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Objective To describe characteristics associated with repeated unplanned extubations, short-term complications and outcomes, and longer-term morbidities including acquired subglottic stenosis. Study design Cohort study including neonates admitted to a tertiary care neonatal intensive care unit who experienced an unplanned extubation in a 5-year period. Results We reviewed 588 events involving 300 patients. Ten percent had airway trauma with reintubation, 42% required ≥2 reintubation attempts, and 39% led to increased baseline oxygen. Increased odds of repeated events were seen in patients with bronchopulmonary dysplasia and were associated with higher rates of tracheostomy and longer length of stay. The 9% of patients diagnosed with acquired subglottic stenosis had more unplanned extubations, higher rates of airway trauma and tracheitis, and were an older gestational age at birth. Conclusion Unplanned extubations lead to short-and long-term morbidities. Certain patient characteristics are associated with increased odds of repeated events and the development of acquired subglottic stenosis.

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To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. STUDY DESIGN: Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. RESULTS: Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. CONCLUSION: Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.

There are several pulmonary hypertensive diseases that affect the neonatal population, including persistent pulmonary hypertension of the newborn (PPHN) and bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH). While the indication for inhaled nitric oxide (iNO) use is for late-preterm and term neonates with PPHN, there is a suboptimal response to this pulmonary vasodilator in ~40% of patients. Additionally, there are no FDA-approved treatments for BPD-associated PH or for preterm infants with PH. Therefore, investigating mechanisms that alter the nitric oxide-signaling pathway has been at the forefront of pulmonary vascular biology research. In this review, we will discuss the various mechanistic pathways that have been targets in neonatal PH, including NO precursors, soluble guanylate cyclase modulators, phosphodiesterase inhibitors and antioxidants. We will review their role in enhancing NO-signaling at the bench, in animal models, as well as highlight their role in the treatment of neonates with PH.