Supplementary Material for: Outcome of Preterm Neonates with a Birth Weight <1,500 g with Severe Hypoxemic Respiratory Failure Rescued by Inhaled Nitric Oxide Therapy and High-Frequency Oscillatory Ventilation

Background: Despite being an experimental therapy in preterm neonates, inhaled nitric oxide (iNO) is used as a rescue therapy when high-frequency oscillatory ventilation (HFOV) and other conventional therapies fail. Objective: We aimed to determine the outcomes of very-low-birth-weight (VLBW) neonates with hypoxemic respiratory failure (HRF) who had received iNO after maximal conventional therapies. Methods: We retrospectively reviewed preterm neonates (<33 weeks of gestation with a birth weight <1,500 g) who had all received HFOV and then iNO from March 1, 2009 to April 1, 2014 at the Royal Alexandra Hospital. We collected demographic and clinical parameters, doses, duration and response to iNO, survival to neonatal intensive care unit (NICU) discharge, major complications, and neurodevelopmental outcome at 18-24 months of corrected age. Results: During the study period, 1,168 eligible preterm neonates were admitted; 155 (13%) had HRF treated with HFOV, of whom 47 (30%) received iNO. The baseline characteristics between the 24 survivors and 23 nonsurvivors were not different. Survivors had a greater decrease in oxygenation index than nonsurvivors (61 vs. 33%) after 6 h of iNO (p = 0.003). The causes of death were refractory hypoxemia (8), multi-organ failure (7), treatment withdrawal (6), and others (2). During the NICU stay, 23 survivors (96%) developed complications. At 18-24 months, 7 (29%) had significant disabilities. Conclusions: Of the VLBW neonates with severe HRF rescued by HFOV and iNO, many survived without neurodevelopmental disability at early childhood, despite multiple short-term complications. Further research is necessary to understand the clinical course and risk factors of adverse outcomes and to improve the management care of these critically ill neonates.