Feasibility of Using Bubble Nasal Intermittent Pressure Ventilation Using the Neovent in Low-resource Settings

BACKGROUND INFORMATION AND RATIONALE Infant respiratory distress is a leading cause of under-5 mortality worldwide, resulting in over one million infant deaths every year. Over 99% of these deaths occur in low to middle income countries For these vulnerable infants, noninvasive ventilation is preferred as it is associated with lower rates of chronic lung disease and ventilator-associated-pneumonia than invasive modes of ventilation. Widely used methods of noninvasive respiratory support for infants in respiratory distress include Nasal Continuous Positive Airway Pressure (NCPAP) and Nasal Intermittent Positive Pressure Ventilation (NIPPV). NCPAP consists of delivering a constant pressure, typically from 5 - 8 cm H2O, to recruit and stabilize the alveoli and improve ventilation and perfusion mismatch. NIPPV provides additional respiratory support with intermittent mandatory ventilation over the constant baseline pressure, e.g. 15 cm H2O over 5 cm H2O. The lower pressure is termed "P low" and the higher pressure is termed "P high". This additional respiratory support reduces the work of breathing3. In comparison with NCPAP, NIPPV has been shown to decrease the need for ventilation of preterm infants, decrease post-extubation failure and may further decrease the frequency of apneic episodes.

Bubble NCPAP is a simple, non-electric and easy to use means of delivering CPAP that has been successfully implemented across low and high resource settings 7,8. Unfortunately, until the present, there has not been an analogous simple, non-electric and easy to use means to deliver NIPPV. Conventional NIPPV equipment costs $10,000+, requires continuous electricity and requires many highly trained operators (physician, respiratory therapist, biomedical equipment technician), all of which serve as barriers to implementation in resource- constrained settings.

To address these barriers, a novel bubble NIPPV device, NeoVent, has been developed and shown to be both feasible and safe in a higher resourced nursery. With NeoVent, clinicians can independently set key parameters: upper level of pressure, lower level of pressure and rate (cycles/min). The technology is non-electric and visually intuitive to set up and operate. In the ASL 6000 infant lung simulator, NeoVent delivered comparable volumes and pressure waveforms as conventional ventilators. In sedated rabbits, NeoVent was able to achieve comparable ventilation, as demonstrated by arterial blood gas values, as a conventional ventilator13. In a first-in-human study of safety, NeoVent achieved a similar safety profile to bubble NCPAP 14. In a larger follow on study of safety, NeoVent again achieved a similar safety profile as bubble CPAP. Results have been published/presented in peer-reviewed forums including Pediatric Research, Respiratory Care, American Academy of Pediatrics, Indian Academy of Pediatrics, Canadian Society of Respiratory Therapists, Medicins Sans Frontieres and USAID/Gates Foundation's Grand Challenges in Global Health.

The investigators believe NIPPV using the Neovent is feasible for use by healthcare providers in lower resourced nurseries in Nepal and Nigeria; that NIPPV provided by Neovent will be as safe as breathing support providing by machine CPAP and newborns on Neovent will not have more nasal irritation or nose bleeds, more stomach problems, or air around their lungs than newborns on machine CPAP.

Primary Aim: Among infants (≤ 28 days) with respiratory distress settings, bubble NIPPV using the Neovent is feasible for use by healthcare providers in lower resourced nurseries in Nigeria and Nepal. This will test the hypothesis that at least 80% of healthcare providers' (clinicians/nurses) in lower resourced nurseries in Nigeria and Nepal can 1) set up, 2) operate and 3) troubleshoot bubble NIPPV using the Neovent and will be qualitatively assessed 3 months after introduction of the NIPPV in their NICU-based on survey/questionnaire/and demonstration.