Prospective Crossover Comparison of Work of Breathing During Non-invasive Ventilation: Neurally Adjusted Ventilatory Assist (NAVA) Versus Nasal Intermittent Positive Pressure Ventilation (NIPPV) in Premature Neonates

Background/Rationale:

Historically, respiratory insufficiency and respiratory failure have been frequent sources of morbidity and mortality in premature neonates. Intubation for invasive mechanical ventilation has been a life-saving therapy for many of these patients, but is not without risks. These risks include pulmonary complications such as volutrauma, extrapulmonary air leak syndromes, and traumatic injury to the large airways; non-pulmonary complications such as retinopathy of prematurity; and long-term complications such as bronchopulmonary dysplasia [Miller, Badiee]. Concern over these effects of prolonged mechanical ventilation has led to the development of non-invasive forms of respiratory support.

Non-invasive ventilation (NIV) is a frequently used modality of respiratory support for premature neonates in the setting of respiratory insufficiency or recent weaning from invasive ventilation. Synchronized NIV is effective at decreasing respiratory effort as compared to unsynchronized NIV and nasal continuous positive airway pressure (NCPAP) [Chang]. Synchronizing NIV in premature neonates to the patient's own respiratory efforts is difficult because of the large air leaks, weak inspiratory efforts, and high respiratory rates inherent to this population [Vignaux].

A novel method of synchronization, neurally adjusted ventilatory assist (NAVA) uses electrodes on a functional naso/orogastric tube (Edi catheter) to detect diaphragm contractions and time the onset, duration, and peak inspiratory pressure of supporting breaths with the electrical activity of the diaphragm (Edi) [Sinderby]. NAVA can be used with both invasive and non-invasive ventilation modalities, and there have been several small studies examining invasive NAVA in children and adults [Stein, de la Olivia]. Fewer studies have examined NIV NAVA in these populations, and only two clinical trials have examined NIV NAVA in premature neonates [Beck, Lee]. Beck and colleagues in Canada showed feasibility and preservation of synchrony during NIV NAVA in premature neonates [Beck]. Lee and colleagues in Korea showed fewer asynchrony events, lower trigger delay, and lower peak inspiratory pressures with NIV NAVA compared to non-invasive pressure support ventilation in premature neonates [Lee]. Neither study examined work of breathing (WOB) in preterm neonates ventilated with NIV NAVA.

Work of breathing during assisted ventilation is the portion of the driving pressure for ventilation contributed by the patient's respiratory muscles. A research team at Arkansas Children's Hospital was able to demonstrate that NAVA achieves reduced response time, work of breathing, and asynchrony with neurally triggered breaths as compared to pneumatically triggered breaths in an animal model [Heulitt]. This team was also able to show similar results in a clinical study of intubated pediatric patients with bronchiolitis [Clement]. A recently completed study at this institution looked at work of breathing in neonatal pigs comparing NIV NAVA with the unsynchronized nasal intermittent positive pressure (NIPPV) mode currently used at this hospital. Using the pressure-time product (PTP) as a measure of WOB this study was able to show that WOB was lower with NAVA. The PTP cannot be reliably used in infants on NIV because the nasal prong interface allows large air leaks at the nose and mouth, which interfere with accurate measurements.