Short-term effects of synchronized vs. non-synchronized NIPPV in preterm infants: study protocol for an unmasked randomized crossover trial.

Background: Non-invasive ventilation (NIV) has been recommended as the best respiratory support for preterm infants with respiratory distress syndrome (RDS). However, the best NIV technique to be used as first intention in RDS management has not yet been established. Nasal intermittent positive pressure ventilation (NIPPV) may be synchronized (SNIPPV) or non-synchronized to the infant's breathing efforts. The aim of the study is to evaluate the short-term effects of SNIPPV vs. NIPPV on the cardiorespiratory events, trying to identify the best ventilation modality for preterm infants at their first approach to NIV ventilation support.

Methods: An unmasked randomized crossover study with three treatment phases was designed. All newborn infants < 32 weeks of gestational age with RDS needing NIV ventilation as first intention or after extubation will be consecutively enrolled in the study and randomized to the NIPPV or SNIPPV arm. After stabilization, enrolled patients will be alternatively ventilated with two different techniques for two time frames of 4 h each. NIPPV and SNIPPV will be administered with the same ventilator and the same interface, maintaining continuous assisted ventilation without patient discomfort. During the whole duration of the study, the patient's cardiorespiratory data and data from the ventilator will be simultaneously recorded using a polygraph connected to a computer. The primary outcome is the frequency of episodes of oxygen desaturation. Secondary outcomes are the number of the cardiorespiratory events, FiO necessity, newborn pain score evaluation, synchronization index, and thoracoabdominal asynchrony. The calculated sample size was of 30 patients.

Discussion: It is known that NIPPV produces a percentage of ineffective acts due to asynchronies between the ventilator and the infant's breaths. On the other hand, an ineffective synchronization could increase work of breathing. Our hypothesis is that an efficient synchronization could reduce the respiratory work and increase the volume per minute exchanged without interfering with the natural respiratory rhythm of the patient with RDS. The results of this study will allow us to evaluate the effectiveness of the synchronization, demonstrating whether SNIPPV is the most effective non-invasive ventilation mode in preterm infants with RDS at their first approach to NIV ventilation.

Trial Registration: ClinicalTrials.gov NCT03289936 . Registered on September 21, 2017.