Breathing Variability and NAVA in Neonates

Study Overview
=================
Brief Summary
-----------------
The current study is a crossover trial, aiming at evaluating the effect of NAVA -NIV compared to Nasal Intermittent Positive Pressure Ventilation (PC-NIV) at the same level of peak inspiratory pressure, in terms of: breath-by-breath variability of tidal breathing amplitude, variability of the other breathing patterns; lung mechanics; gas exchange; rate of episodes of apnea; bradycardia and desaturations; respiratory asynchrony and comfort, in preterm infants < 37+0 weeks+days post-menstrual age.

Detailed Description
-----------------
Preterm infants matching the inclusion criteria (listed elsewhere) will be enrolled in a cross- over trial of two modes of non-invasive respiratory support: nasal intermittent positive pressure ventilation (PC-NIV) and NAVA NIV (Sevo-n Neonatal Ventilator, GETINGE, Solna, Sweden). Parental consent will be collected prior to the study. A 20-minute registration of ventilator parameters during assistance on NAVA-NIV will allow calculating the mean PIP (peak inspiratory pressure), in order to compare the two modes at the same level of PIP. The ventilator settings other than PIP (i.e. FiO2 (fraction of inspired oxygen), PEEP (positive end-expiratory pressure), IT (inspiratory time), RR (respiratory rate), NAVA level) will be based on the setting optimized by the attending physicians prior to the study entry. FiO2 will be adjusted in order to maintain SpO2 88-93% in infants ≤ 32 weeks of postconceptional age, 90-95% in infants > 32 weeks of postconceptional age. Infants will then receive a randomized sequence of 1-hour assistance by NAVA NIV and 1-hour assistance PC-NIV or vice-versa. Infants will receive respiratory support in a standardized supine position during the study period. Two, high-resolution, small cameras will be placed in the infant's incubator to detect chest and abdominal movements, by means of two markers placed on the infant's chest and abdomen. Ventilators parameters (flow, pressure, volume, the electrical activity of the diaphragm), vital signs (SpO2, HR (heart rate), ABP( arterial blood pressure)), transcutaneous gases, changes in end-expiratory lung volume will be collected continuously. Episodes of apnea, bradycardia or desaturations and the number of interventions required by the nurses and the attending physicians during the study (e.g. adjustment of the interface, suctioning, interventions to provide comfort or optimize the respiratory support...) will be also collected during the study. Patients' comfort will be assessed at the end of each sequence by the attending nurse by means of the COMFORT scale. Lung mechanics will be measured at the end of each sequence by means of the Forced Oscillation Technique. Data will be then analysed and compared offline.

Official Title
-----------------
Breathing Pattern Variability in Preterm Infants: Effect of Non-invasive Neurally Adjusted Ventilatory Assist (NAVA-NIV) Versus Nasal Intermittent Positive Pressure Ventilation (PC-NIV), a Crossover Study

Conditions
-----------------
Neonatal Respiratory Distress Syndrome, Prematurity

Intervention / Treatment
-----------------
* Other: Respiratory support: NAVA -NIV and PC-NIV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: preterm birth < 37 weeks of gestational age need of non-invasive respiratory support parental consent Exclusion Criteria: Major congenital abnormalities of the cardio-respiratory systems Severe Respiratory Failure requiring intubation and mechanical ventilation at the time of the study; pH < 7.25 pCO2> 65 mmHg; pulmonary hypertension of the newborn requiring pharmacological treatment (Nitric Oxide, Sildenafil) Hypoxic-Ischaemic Encephalopathy, neurological disorders which may compromise the integrity of the neural transmission from the brain to the diaphragm Contraindication to orogastric tube insertion (e.g. oesophageal atresia, gastric perforation...) Haemodynamic instability requiring inotropic agents Any condition that would expose the patient to undue risk as deemed by the attending physician

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 3 Months

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Population<br>All the infants enrolled in the study will receive 1 h of NAVA-NIV and 1h PC-NIV in a cross-over study design | Other: Respiratory support: NAVA -NIV and PC-NIV<br>* The infants enrolled will receive respiratory assistance by NAVA-NIV and PC-NIV in a randomized order<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in breath-by-breath variability of tidal breathing amplitude | Tidal breathing amplitude will be recorded continuously by mean of two, high-resolution cameras placed inside the infant's incubator and skin (non-invasive) markers. Data will be analysed a posteriori applying the DFA (Detrended Fluctuation Analysis) technique. | over the last 30 minutes of each step (crossover trial, 2 steps, 1 hour-step) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Rate | Respiratory rate (breaths/min) will be recorded from the ventilator | at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step | 
| Inspiratory Time | Inspiratory time (msec) will be recorded from the ventilator tracing | at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step | 
| Duty Cycle | Duty Cycle (Inspiratory Time/ Total Time), will be calculated from the ventilator tracing | at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step | 
| Total Respiratory System Oscillatory Resistance | Total Respiratory System Oscillatory Resistance will be measured by the Forced Oscillation Technique (FOT) at the end of each step, by superimposing to the ventilator waveform an oscillatory pressure of small amplitude at 10 Hz (Fabian, ACUTRONIC Medical Systems AG, Switzerland). | at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step) | 
| Total Respiratory System Oscillatory Reactance | Total Respiratory System Oscillatory Reactance will be measured by the Forced Oscillation Technique (FOT) at the end of each step, by superimposing to the ventilator waveform an oscillatory pressure of small amplitude at 10 Hz (Fabian, ACUTRONIC Medical Systems AG, Switzerland). | at the end of each 1-hour step of the trial (crossover trial, 2 steps, 1 hour-step) | 
| SpO2/FiO2 (Fraction on inspired oxygen) | SpO2 and FiO2 will be monitored continuously and FiO2 will be adjusted to the target SpO2 88-93% in infants ≤ 32 weeks of postconceptional age, SpO2 90-95% in infants > 32 weeks of postconceptional age. | at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step | 
| tpCO2, Transcutaneous Carbon Dioxide Partial Pressure (mmHg) | tpCO2 will be monitrored continuously over the study period and recorded at specific time points | at the beginning of the study, at 10minutes, 20minutes, 30minutes, 35minutes, 40minutes, 45minutes, 50minutes, 55minutes, for each step, in a 2-step crossover trial, 1-hour step | 
| Rate of apneas, desaturations, bradycardias | Episodes of apnoeas, desaturations, bradycardias will be recorded over each study period | over 1 hour, for each step (in a 2-step crossover trial, 1-hour step) | 
| Rate of patient-ventilator asynchronies | Patient-ventilator asynchronies will be calculated by continuous recording of ventilator parameters (flow, pressure, volume and electrical diaphragmatic activity) and by continuous recording of abdominal and chest movements by high resolution cameras placed in the incubators and skin markers on abdomen and chest | over 1 hour, for each step (in a 2-step crossover trial, 1-hour step) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preterm Infant, Respiratory Distress Syndrome, Non-invasive respiratory Support, Neurally Adjust Respiratory Assist (NAVA), Nasal Intermittent Positive Pressure Ventilation