Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome

Study Overview
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Brief Summary
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Non-invasive ventilation can allow to avoid intubation and improve outcomes in moderate-to-severe COVID-19-associated acute respiratory distress-syndrome (ARDS). Data on NIV parameters adjustment based on expanded respiratory and gas exchange monitoring in COVID-19 associated ARDS is limited. Appropriate adjustment of the inspiratory positive airway pressure (IPAP) set as a point of the balance between minimal work of breathing (minimum point of W.Patrick scale for assessment of the accessory respiratory muscles and minimum diaphragm thickening fraction) and minimum tidal volume, and respiratory rate can decrease NIV failure in moderate-to-severe COVID-ARDS. The objective of the study is to evaluate the ability of non-invasive ventilation guided with expanded respiratory monitoring to decrease the intubation rate in in moderate-to-severe COVID-ARDS.

Detailed Description
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In December 2019, an outbreak of a novel coronavirus emerged in Wuhan, China and rapidly spread worldwide. The World Health Organization (WHO) declared the outbreak a pandemic on March 11th, 2020. The clinical disease (COVID-19) results in critical illness in about 5% of patients with predominant acute respiratory failure. The objective of the study is to evaluate the ability of non-invasive ventilation guided with expanded respiratory monitoring to decrease the intubation rate in in moderate-to-severe COVID-ARDS. Investigators will set IPAP as a point of the balance between minimal work of breathing (minimum point of W.Patrick scale for assessment of the accessory respiratory muscles, and minimum diaphragm thickening fraction) and minimum tidal volume, and respiratory rate. Investigators will set expiratory pressure at 8-10 cm of water and the inspiratory oxygen fraction (FiO2) to reach oxygen saturation by pulse oximetry (SpO2) 95%. All gas exchange measurements will be set at IPAP level. For gas exchange assessment investigators will measure partial oxygen tension in the arterial blood (PaO2), partial carbon dioxide tension in arterial blood (PaCO2), end-tidal carbon dioxide tension (PetCO2), then will calculate PAO2/FiO2, alveolar dead space (Vd alv) and ventilatory ratio (VR). Investigators will measure expiratory tidal volume (VT), respiratory rate (RR), peak inspiratory flow (PIF) and inspiratory time at 3 levels: at the set IPAP, at IPAP+4 cm of water and at IPAP-4 cm of water. Measurements will be repeated on day 1, 3, 5, 7, 14 and 21 of NIV. NIV failure is determined as one of the following at set IPAP 26 cm of water and FiO2 100%: fatigue, Patrick scale 5 points, SpO2<92%, apnoea, hemodynamic instability or Glasgow coma score <14 points. In patients with NIV failure after intubation and every 7 day after intubation investigators will measure plateau pressure and calculate the driving pressure at PEEP 8-10-12-14 cm of water and VT 6 ml/kg predicted body weight (PBW), and VT+100 ml and VT+200 ml at PEEP 8 cm of water, plot static pressure volume-curve at positive end-expiratory pressure (PEEP) 5 and 14 cm of water, and perform electro impedance tomography. This study is an observational trial in the ICU of the University hospital.

Official Title
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Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome to Prevent Tracheal Intubation: the COVID-NIV Study

Conditions
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ARDS, Covid19

Intervention / Treatment
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* Diagnostic Test: Respiratory monitoring
* Diagnostic Test: Respiratory muscles ultrasound
* Diagnostic Test: Electro impedance tomography
* Diagnostic Test: Capnography
* Diagnostic Test: Arterial blood gas
* Diagnostic Test: Quasistatic pressure-volume curve


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least one of the following criteria: fatigue, Patrick scale 5 points, SpO2<92% on standard oxygen therapy (<15 l/min) or continuous positive airway pressure (CPAP)-therapy with oxygen flow<15 l/min Exclusion Criteria: pregnancy age less than 18 or more than 80 years life-threatening heart rhythm abnormalities and/or systolic blood pressure < 80 mmHg despite norepinephrine at a dose > 2 µg/kg/min primary lung diseases (e.g. interstitial lung diseases, lung emphysema) or tumour metastases in lungs chronic decompensated diseases with extrapulmonary organ dysfunction (tumour progression, liver cirrhosis, congestive heart failure) Glasgow cona score < 14 inability to swallow upper airways obstruction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Respiratory monitoring|Measurement of the tidal volume, peak inspiratory flow, inspiratory time, respiratory rate and the pressure gap during triggering on NIV and plateau pressure on mechanical ventilation|
|Diagnostic Test: Respiratory muscles ultrasound|Measurement of the diaphragm thickening fraction, assessment of the contraction of scalene and sternocleidomastoid muscles|
|Diagnostic Test: Electro impedance tomography|Measurement of the lung impedance changes in 4 quadrants, measurement of regional ventilation delay in 4 quadrants|
|Diagnostic Test: Capnography|Measurement of end-tidal carbon dioxide tension|
|Diagnostic Test: Arterial blood gas|Measurement of the oxygen partial pressure and the carbon dioxide partial pressure|
|Diagnostic Test: Quasistatic pressure-volume curve|Quasistatic pressure-volume curve|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intubation rate | Frequency of NIV failure | On day 28 | 
| Mortality | Mortality on day 28 | On day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio | Calculation of the arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio using arterial oxygen tension measurement | Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation | 
| Change in ventilatory ratio | Measurement of arterial carbon dioxide tension, minute ventilation and calculation of ventilatory ratio | Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation | 
| Change in alveolar dead space | Calculation of the alveolar dead space using end-tidal carbon dioxide measurement and arterial carbon dioxide tension measurement | Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation | 
| Change in tidal volume | Measurement of exhaled tidal volume | Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation | 
| Change in accessory respiratory muscles workload | Calculation of the Patrick's scale (minimum 0 points, maximum 5 points, more points means worse outcome) | Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation |