Non-invasive inhaled nitric oxide in the treatment of hypoxemic respiratory failure in term and preterm infants

OBJECTIVES: Inhaled nitric oxide (iNO) is effective in conjunction with tracheal intubation (TI) and mechanical ventilation (MV) for treating arterial pulmonary hypertension and hypoxemic respiratory failure (HRF) in near-term and term newborns. Non-invasive respiratory support with nasal continuous positive airway pressure (CPAP) is increasingly used to avoid morbidity associated with TI and MV, yet the effectiveness of iNO delivery via nasal CPAP remains unknown. To evaluate the effectiveness of iNO delivered via the bubble nasal CPAP system in term and preterm newborns with HRF. STUDY DESIGN: Electronic medical records from all infants admitted to the neonatal intensive care unit (NICU) during 2005 to 2014 (n=10, 895) were screened for treatment with iNO therapy for HRF. Detailed data on population characteristics and cardiorespiratory, iNO and respiratory support indices were abstracted for all infants, who were administered iNO non-invasively using bubble nasal CPAP. Change in relevant indices at baseline (before initiating non-invasive iNO) and at 3, 6, 12 and 24 h after non-invasive iNO therapy were analyzed using repeated measures analysis of variance. RESULTS: Of 795 infants treated with iNO (7.3% of total NICU admissions) over a 10-year period, 107 infants (13.4% of iNO treated) with birth weight 2448 +/- 1112 g and gestational age 35.3 +/- 5.8 weeks received iN0 non-invasively. 25 infants received iNO exclusively non-invasively, whereas in remaining 82 infants non-invasive route followed invasive delivery via TI and MV. Indications for using non-invasive iNO included idiopathic pulmonary hypertension (39%), congenital heart disease (37%), bronchopulrnonary dysplasia (10%), meconium aspiration syndrome (9%) and congenital diaphragmatic hernia (5%). Over the 24 h following initiation of non-invasive iNO, fractional:oxygen requirements decreased (0.38 to 0.32; P<0.0005) and SpO(2) increased (90.7 to 91.6%; P < 0.01) with no significant changes in heart rate, respiratory rate, blood pressure, pH and PaCO2. On average non-invasive iNO was initiated on day of life 9 with a maximal dose was 20 p.p.m. The average duration of iNO therapy and the duration over which it was weaned off were 134 and 51 h, respectively. Analysis of environmental gases during non-invasive iNO therapy revealed median ambient nitrogen dioxide and nitric oxide levels of 0.30 and 0.01 p.p.m., respectively. CONCLUSIONS: Initiation of iNO in infants on bubble nasal CPAP or continuation of iNO in infants transitioning from MV to bubble nasal CPAP is associated with improved oxygenation during HRF in term and preterm infants. Non-invasive iNO may have a synergistic effect with airway recruitment strategies such as nasal CPAP.