Effects of Non-invasive Ventilation With Helium-oxygen Mixture in Premature Infants With Respiratory Distress Syndrome

Study Overview
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Brief Summary
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The use of a mixture of helium with oxygen (heliox) as a breathing gas may be beneficial due to its unique physical properties, such as low density and high carbon dioxide (CO2) diffusion coefficient. In previous studies in neonates with respiratory failure, conventional ventilation with heliox was associated with improved oxygenation and selected respiratory parameters. The use of heliox may increase the effectiveness of intermittent nasal positive pressure ventilation (NIPPV), but knowledge about the effects of such therapy on newborns is limited.The use of non- invasive neurally adjusted ventilatory assist (NIV-NAVA) allows synchronization and assessment of electrical activity of the diaphragm (EaDI) during heliox administration in premature babies with respiratory failure.

Detailed Description
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Aim of the study was to assess of the impact of non-invasive ventilation with heliox on respiratory function, diaphragm bioelectrical activity, cerebral oxygenation and selected vital signs in premature neonates with respiratory failure. 23 neonates ≤32 weeks gestational age (GA) were enrolled in the study. Patients were eligible for inclusion when ventilated due to respiratory failure, and in group 1 (n=12) on NIV as primary modality with oxygen requirement of 0.25-0.4 in the first 72 hours of life, or in group 2 (n=11) ready to extubate according to the given criteria. Newborns were ventilated with NIV NAVA and standard breathing gas (air-oxygen) at baseline. Heliox was introduced for 3 hours, followed by 3 hours of air-oxygen. NAVA level was kept constant and pulse oximeter oxygen saturation (SpO2) kept in range of 90-95%. Recorded parameters included heart rate (HR), SpO2 and cerebral tissue oxygenation (StO2). Selected ventilation parameters: peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), mean airway pressure (MAP), air leakage during NIV, fraction of inspired oxygen (FiO2) as well as electrical activity of the diaphragm (EaDI mean, minimum and maximum) were also acquired. Blood gas analysis was performed in each period of the study. Statistical analysis was completed with ANOVA Friedman's test and single-factor repeated-measures analysis of variance.

Official Title
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Effects of Non-invasive Ventilation With Helium-oxygen Mixture in Premature Infants With Respiratory Distress Syndrome on Pulmonary Function and Electric Activity of the Diaphragm

Conditions
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Respiratory Distress Syndrome, Premature Infants

Intervention / Treatment
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* Drug: heliox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Group 1): GA under 33 weeks GA Need for NIV due to clinical symptoms of respiratory distress in course of RDS FiO2=0.25-0.4 Enrollment within first 72 hours of life Parental consent Inclusion Criteria (Group 2): GA under 33 weeks GA Need for MV due to clinical symptoms of respiratory distress at least one failed attempted extubation Parental consent Exclusion Criteria: Major congenital anomalies Deteriorating pulmonary function despite NIV and the need for intubation and conventional mechanical ventilation (CMV) (Preliminary criteria: pH< 7.22, carbon dioxide partial pressure (pCO2) >65)

Ages Eligible for Study
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Minimum Age: 1 Hour

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>premature infants born < 33 G.A. enrolled in the first 72 hours after birth, with respiratory distress syndrome, requiring non-invasive ventilation with FiO2 <0.4 | Drug: heliox<br>* NIV-NAVA with a conventional gas mixture (air-oxygen) at baseline, 3 hours of NIV-NAVA with heliox and return to NIV-NAVA with air-oxygen.<br>* Other names: helium-oxygen gas mixture;|
| Experimental: Group 2<br>premature infants born < 33 G.A. with respiratory insufficiency requiring mechanical ventilation, after more than 1 failed extubation attempt | Drug: heliox<br>* NIV-NAVA with a conventional gas mixture (air-oxygen) at baseline, 3 hours of NIV-NAVA with heliox and return to NIV-NAVA with air-oxygen.<br>* Other names: helium-oxygen gas mixture;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline minimal electric activity of the diaphragm (EaDI min) | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV, microvolts] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured at baseline | 
| baseline mean electric activity of the diaphragm (EaDI mean) | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured at baseline | 
| baseline maximal electric activity of the diaphragm (EaDI max) | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured at baseline | 
| minimal electric activity of the diaphragm (EaDI min) after 15 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes of heliox ventilation | 
| mean electric activity of the diaphragm (EaDI mean) after 15 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes of heliox ventilation | 
| maximal electric activity of the diaphragm (EaDI max) after 15 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes of heliox ventilation | 
| minimal electric activity of the diaphragm (EaDI min) after 60 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes of heliox ventilation | 
| mean electric activity of the diaphragm (EaDI mean) after 60 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes of heliox ventilation | 
| maximal electric activity of the diaphragm (EaDI max) after 60 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes of heliox ventilation | 
| minimal electric activity of the diaphragm (EaDI min) after 180 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes of heliox ventilation | 
| mean electric activity of the diaphragm (EaDI mean) after 180 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes of heliox ventilation | 
| maximal electric activity of the diaphragm (EaDI max) after 180 minutes of heliox | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes of heliox ventilation | 
| minimal electric activity of the diaphragm (EaDI min) after 15 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes since the return to ventilation with standard mixture | 
| mean electric activity of the diaphragm (EaDI mean) after 15 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes since the return to ventilation with standard mixture | 
| maximal electric activity of the diaphragm (EaDI max) after 15 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 15 minutes since the return to ventilation with standard mixture | 
| minimal electric activity of the diaphragm (EaDI min) after 60 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes since the return to ventilation with standard mixture | 
| mean electric activity of the diaphragm (EaDI mean) after 60 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes since the return to ventilation with standard mixture | 
| maximal electric activity of the diaphragm (EaDI max) after 60 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 60 minutes since the return to ventilation with standard mixture | 
| minimal electric activity of the diaphragm (EaDI min) after 180 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI min [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes since the return to ventilation with standard mixture | 
| mean electric activity of the diaphragm (EaDI mean) after 180 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI mean [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes since the return to ventilation with standard mixture | 
| maximal electric activity of the diaphragm (EaDI max) after 180 minutes of standard mixture | Using the NAVA (neurally adjusted ventilatory assist) module of the Maquet Servo-i ventilator and Servo-tracker software EaDI max [mcV] values will be recorded during the study and their values will be compared between the heliox and air-oxygen NIV (non -invasive ventilation). | measured after 180 minutes since the return to ventilation with standard mixture | 
| baseline PIP (peak inspiratory pressure) | PIP [cm H2O, centimeters of water] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| baseline PEEP (positive end-expiratory pressure) | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| baseline MAP (mean airway pressure) | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| PIP (peak inspiratory pressure) after 15 minutes of heliox | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| PIP (peak inspiratory pressure) after 60 minutes of heliox | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| PIP (peak inspiratory pressure) after 180 minutes of heliox | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| PIP (peak inspiratory pressure) after 15 minutes of standard mixture | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes since the return to ventilation with standard mixture | 
| PIP (peak inspiratory pressure) after 60 minutes of standard mixture | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to ventilation with standard mixture | 
| PIP (peak inspiratory pressure) after 180 minutes of standard mixture | PIP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to ventilation with standard mixture | 
| PEEP (positive end-expiratory pressure) after 15 minutes of heliox | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| PEEP (positive end-expiratory pressure) after 60 minutes of heliox | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| PEEP (positive end-expiratory pressure) after 180 minutes of heliox | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| PEEP (positive end-expiratory pressure) after 15 minutes of standard mixture | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes since the return to ventilation with standard mixture | 
| PEEP (positive end-expiratory pressure) after 60 minutes of standard mixture | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to ventilation with standard mixture | 
| PEEP (positive end-expiratory pressure) after 180 minutes of standard mixture | PEEP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to ventilation with standard mixture | 
| MAP (mean airway pressure) after 15 minutes of heliox | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| MAP (mean airway pressure) after 60 minutes of heliox | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| MAP (mean airway pressure) after 180 minutes of heliox | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| MAP (mean airway pressure) after 15 minutes of standard ventilation | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to ventilation with standard mixture | 
| MAP (mean airway pressure) after 60 minutes of standard ventilation | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to ventilation with standard mixture | 
| MAP (mean airway pressure) after 180 minutes of standard ventilation | MAP [cm of water / cm H2O] will be recorded by Servo-tracker software and the values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to ventilation with standard mixture | 
| baseline NIV leakage | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| NIV leakage after 15 minutes of heliox | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| NIV leakage after 60 minutes of heliox | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| NIV leakage after 180 minutes of heliox | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| NIV leakage after 15 minutes of standard mixture | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes since the return to ventilation with standard mixture | 
| NIV leakage after 60 minutes of standard mixture | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to ventilation with standard mixture | 
| NIV leakage after 180 minutes of standard mixture | gas leakage fraction [%] during NIV (non-invasive ventilation) recorded by Servo-tracker software their values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to ventilation with standard mixture | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline cerebral oxygenation | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| Cerebral oxygenation after 15 minutes of heliox | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| Cerebral oxygenation after 60 minutes of heliox | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| Cerebral oxygenation after 180 minutes of heliox | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| Cerebral oxygenation after 15 minutes of standard mixture | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes since the return to standard mixture ventilation | 
| Cerebral oxygenation after 60 minutes of standard mixture | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to standard mixture ventilation | 
| Cerebral oxygenation after 180 minutes of standard mixture | Cerebral tissue oxygen saturation (StO2; [%]) measured with near infrared spectroscopy (NIRS) - NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA - their values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to standard mixture ventilation | 
| baseline oxygen requirements | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded at baseline | 
| oxygen requirements after 15 minutes of heliox | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 15 minutes of heliox ventilation | 
| oxygen requirements after 60 minutes of heliox | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 60 minutes of heliox ventilation | 
| oxygen requirements after 180 minutes of heliox | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 180 minutes of heliox ventilation | 
| oxygen requirements after 15 minutes of standard ventilation | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 15 minutes since the return to standard mixture ventilation | 
| oxygen requirements after 60 minutes of standard ventilation | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 60 minutes since the return to standard mixture ventilation | 
| oxygen requirements after 180 minutes of standard ventilation | Fraction of inspired oxygen (FiO2) will be recorded during heliox and air-oxygen NIV to maintain the saturation assessed by pulse oximetry (SpO2) in 90-95% range; their values will be compared between the phases of the study | recorded after 180 minutes since the return to standard mixture ventilation | 
| baseline capillary blood gas analysis | Cobas B 221; Roche, Germany; the values will be compared between the heliox and air-oxygen NIV. | blood samples drawn at baseline | 
| capillary blood gas analysis after 3 hours of heliox | Cobas B 221; Roche, Germany; the values will be compared between the heliox and air-oxygen NIV. | blood samples drawn after 3 hours of heliox ventilation | 
| capillary blood gas analysis after 3 hours of standard mixture | Cobas B 221; Roche, Germany; the values will be compared between the heliox and air-oxygen NIV. | blood samples drawn after 3 hours of standard mixture ventilation | 
| baseline heart rate | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| heart rate after 15 minutes of heliox | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes of heliox ventilation | 
| heart rate after 60 minutes of heliox | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes of heliox ventilation | 
| heart rate after 180 minutes of heliox | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes of heliox ventilation | 
| heart rate after 15 minutes of standard mixture | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 15 minutes since the return to standard mixture ventilation | 
| heart rate after 60 minutes of standard mixture | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 60 minutes since the return to standard mixture ventilation | 
| heart rate after 180 minutes of standard mixture | heart rate (HR, [bpm / beats per minute]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA), values will be compared between the heliox and air-oxygen NIV. | measured after 180 minutes since the return to standard mixture ventilation | 
| baseline oxygen saturation | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured at baseline | 
| oxygen saturation after 15 minutes of heliox | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 15 minutes after heliox ventilation | 
| oxygen saturation after 60 minutes of heliox | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 60 minutes after heliox ventilation | 
| oxygen saturation after 180 minutes of heliox | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 180 minutes after heliox ventilation | 
| oxygen saturation after 15 minutes of standard mixture | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 15 minutes since the return to standard mixture ventilation | 
| oxygen saturation after 60 minutes of standard mixture | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 60 minutes since the return to standard mixture ventilation | 
| oxygen saturation after 180 minutes of standard mixture | SpO2 (peripheral capillary oxygen saturation, [%]) measured by NONIN Sen Smart Model X-100, Nonin Medical Inc., Plymouth, USA) and the values will be compared between the heliox and air-oxygen NIV. | measured 180 minutes since the return to standard mixture ventilation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-invasive ventilation, NIRS, EaDI, Edi, NIV, NAVA, helium-oxygen, heliox, respiratory distress syndrome (RDS)