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

Respiratory Distress Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04404816
• Other study ID #: 072015
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2017
• Est. completion date: December 2018

Study information

• Verified date: June 2020
• Source: Poznan University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Premature Birth
• Premature Infants
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• heliox
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.

Locations

Country	Name	City	State
Poland	Gynecological and obstetric teaching hospital, Departament of Neonatology, Polna street 33	Poznan	Great Poland

Sponsors (2)

Lead Sponsor	Collaborator
Poznan University of Medical Sciences	European Society for Paediatric Research

Country where clinical trial is conducted

Poland, 

References & Publications (13)

Beck J, Reilly M, Grasselli G, Qui H, Slutsky AS, Dunn MS, Sinderby CA. Characterization of neural breathing pattern in spontaneously breathing preterm infants. Pediatr Res. 2011 Dec;70(6):607-13. doi: 10.1203/PDR.0b013e318232100e. — View Citation

Brooks LJ, DiFiore JM, Martin RJ. Assessment of tidal volume over time in preterm infants using respiratory inductance plethysmography, The CHIME Study Group. Collaborative Home Infant Monitoring Evaluation. Pediatr Pulmonol. 1997 Jun;23(6):429-33. — View Citation

Colnaghi M, Pierro M, Migliori C, Ciralli F, Matassa PG, Vendettuoli V, Mercadante D, Consonni D, Mosca F. Nasal continuous positive airway pressure with heliox in preterm infants with respiratory distress syndrome. Pediatrics. 2012 Feb;129(2):e333-8. doi: 10.1542/peds.2011-0532. Epub 2012 Jan 30. — View Citation

Elleau C, Galperine RI, Guenard H, Demarquez JL. Helium-oxygen mixture in respiratory distress syndrome: a double-blind study. J Pediatr. 1993 Jan;122(1):132-6. Erratum in: J Pediatr 1993 Aug;123(2):336. — View Citation

Jassar RK, Vellanki H, Zhu Y, Hesek A, Wang J, Rodriguez E, Wu J, Shaffer TH, Wolfson MR. High flow nasal cannula (HFNC) with Heliox decreases diaphragmatic injury in a newborn porcine lung injury model. Pediatr Pulmonol. 2014 Dec;49(12):1214-22. doi: 10.1002/ppul.23000. Epub 2014 Feb 5. — View Citation

Kuligowski J, Escobar J, Quintás G, Lliso I, Torres-Cuevas I, Nuñez A, Cubells E, Rook D, van Goudoever JB, Vento M. Analysis of lipid peroxidation biomarkers in extremely low gestational age neonate urines by UPLC-MS/MS. Anal Bioanal Chem. 2014 Jul;406(18):4345-56. doi: 10.1007/s00216-014-7824-6. Epub 2014 May 11. — View Citation

Kuligowski J, Torres-Cuevas I, Quintás G, Rook D, van Goudoever JB, Cubells E, Asensi M, Lliso I, Nuñez A, Vento M, Escobar J. Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach. PLoS One. 2014 Apr 2;9(4):e93703. doi: 10.1371/journal.pone.0093703. eCollection 2014. — View Citation

Nawab US, Touch SM, Irwin-Sherman T, Blackson TJ, Greenspan JS, Zhu G, Shaffer TH, Wolfson MR. Heliox attenuates lung inflammation and structural alterations in acute lung injury. Pediatr Pulmonol. 2005 Dec;40(6):524-32. — View Citation

Oei GT, Weber NC, Hollmann MW, Preckel B. Cellular effects of helium in different organs. Anesthesiology. 2010 Jun;112(6):1503-10. doi: 10.1097/ALN.0b013e3181d9cb5e. Review. — View Citation

Sinderby C, Beck J, Spahija J, Weinberg J, Grassino A. Voluntary activation of the human diaphragm in health and disease. J Appl Physiol (1985). 1998 Dec;85(6):2146-58. — View Citation

Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Halliday HL; European Association of Perinatal Medicine. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants--2013 update. Neonatology. 2013;103(4):353-68. doi: 10.1159/000349928. Epub 2013 May 31. — View Citation

Szczapa T, Gadzinowski J, Moczko J, Merritt TA. Heliox for mechanically ventilated newborns with bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed. 2014 Mar;99(2):F128-33. doi: 10.1136/archdischild-2013-303988. Epub 2013 Nov 15. — View Citation

Szczapa T, Gadzinowski J. Use of heliox in the management of neonates with meconium aspiration syndrome. Neonatology. 2011;100(3):265-70. doi: 10.1159/000327531. Epub 2011 Jun 23. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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