Nasal High-Frequency Oscillation to Improve Respiratory Stability of Preterm Infants: A Randomized Crossover Study

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Intermittent hypoxia (pulse oximetry saturation <80%) and bradycardia (pulse rate <80 beats per minute) frequently occur in preterm infants, often associated with apnoea of prematurity. Such episodes of hypoxia and re-oxygenation have the potential to trigger a pro-inflammatory cascade leading to multisystem morbidity including retinopathy of prematurity, impaired growth, longer-term cardiorespiratory instability, and poor neurodevelopmental outcome. Widely used treatments such as methylxanthines and continuous positive airway pressure (CPAP) are sometimes insufficient and endotracheal intubation and mechanical ventilation are required. Nasal CPAP is the most widely used from of 'non-invasive' ventilation (NIV) in very preterm infants. NIV refers to respiratory support without the need for an endotracheal tube, usually delivered via nasal prongs. Nasal CPAP is an alternative to mechanical ventilation in preterm infants soon after birth. A meta-analysis comparing early CPAP with intubation and mechanical ventilation showed that CPAP reduce the risk of the combined outcome of death or bronchopulmonary dysplasia (BPD). CPAP failure primarily occurs due to AOP, oxygen requirements pre-specified thresholds, and hypercapnia related to hypoventilation. Ventilation failure in infants treated with CPAP may be due to inadequate alveolar ventilation and carbon dioxide elimination. High-frequency oscillatory ventilation (HFOV) delivered via an endotracheal tube leads to excellent carbon dioxide removal using a tidal volume less than the volume of the dead space. HFOV, which has until recently only been delivered via endotracheal tube, uses oscillations of low amplitude and high frequencies quite different from those of normal respiration. It may cause less lung injury than conventional mechanical ventilation. The combination of HFOV and NIV could provide lung-protection, improved oxygenation, better gas exchange, and reduced rates of AOP compared to NIV alone. Therefore, we aim to assess the effect of nHFO versus CPAP therapy in very preterm infants born <30 weeks’ gestation on the cumulative event rate of all bradycardias (< 80 bpm) and desaturations (< 80%) during a 120-minute recording period for each therapy. We hypothesize that in very preterm infants, nHFO is associated with a significant decrease in the number of bradycardias and desaturations compared with CPAP.