Physiological Effects of Non-invasive Mechanical Ventilation Versus High-flow Nasal Cannula in Critically Ill Patients at High Risk of Extubation Failure

Study Overview
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Brief Summary
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Weaning is one of the most complex challenges in mechanically ventilated patients. Increased work of breathing after extubation would play a central role in weaning failure. Currently, non-invasive ventilation (NIV) is recommended to prevent weaning failure in high-risk patients. On the other hand, high-flow nasal cannula (HFNC), which is a novel system capable of administering gas mixtures (air and oxygen) with a flow of up to 60 liters/min, has been used to prevent weaning failure in this kind of patients. The use of NIV and HFNC after extubation has been evaluated in some clinical studies. However, the evidence is controversial, and the information regarding the physiological effects that each therapy induces in recently extubated patients at high risk of weaning failure is lacking. The goal of this proposal is to compare the acute physiological effects of postextubation NIV versus HFNC in critically ill patients at high risk of weaning failure on relevant mechanisms related to weaning failure: Work of breathing, lung function, ventilation distribution, systemic hemodynamics. This will be a randomized crossover study that will include critically ill mechanically ventilated patients, who fulfill criteria indicating they may be ready for weaning from mechanical ventilation, and in whom a spontaneous breathing trial (SBT) is planned to determine if they should be extubated. After checking eligibility and obtaining informed consent, patients will be monitored with an esophageal catheter (esophageal/gastric pressures to determine work of breathing, and electric activity of diaphragm to determine neuromechanical coupling), and a noninvasive ventilation monitor (electric impedance tomography to assess global and regional ventilation). Work of breathing, lung function, and systemic hemodynamics will be assessed during the SBT. Inclusion in the study will be confirmed only if they pass the SBT and are extubated. During the first 2 hours after extubation, patients will undergo one hour of NIV and one hour of HFNC, with the crossover sequence being randomized previously at the time of inclusion and with assessments repeated at the end of each treatment period.

Official Title
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Postextubation Non-invasive Ventilation Versus High-flow Nasal Cannula in Critically Ill Patients at High Risk of Weaning Failure: a Physiologic Randomized Crossover Study

Conditions
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Weaning From Mechanical Ventilation

Intervention / Treatment
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* Device: Non-invasive ventilation (NIV)
* Device: High-flow nasal cannula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mechanical ventilation (MV) through an orotracheal tube for at least 48 hours PaO2 /FiO2 ratio ≤ 300 mmHg (during the MV period) Potential for weaning Precipitating cause leading to MV in resolution PaO2 /FiO2 ratio ≥ 150 mmHg PEEP ≤ 8 cmH2O pH > 7,25 SpO2 ≥ 90% with FiO2 ≤ 0.4; BPM ≤35 Hemodynamic stability (noradrenaline ≤ 0.1mcg / kg / min and SBP 90-160; HR <140) Temperature <38 ° C Presence of inspiratory effort and appropriate spontaneous cough Decision to perform a spontaneous breathing trial by the attending physician High risk of weaning failure defined by a history of: (i) Previous failed extubation, (ii) Chronic heart or respiratory failure, or (iii) MV ≥ 7 days. Exclusion Criteria: Contraindications to NIV or HFNC, which include abnormalities, trauma or surgery of the face or nose. Contraindications for esophageal balloon catheter insertion (eg. severe coagulopathy, esophageal varices, and history of esophageal or gastric surgery) Contraindication for use of electric impedance tomography (eg. Pacemaker) Tracheostomy Refusal to participate by the attending physician Do not resuscitate order

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A: Non-invasive ventilation - High flow nasal cannula<br>Once participants are extubated they will receive one hour of Non-invasive ventilation followed by one hour of high-flow nasal cannula. | Device: Non-invasive ventilation (NIV)<br>* Non-invasive ventilation will be provided through a mechanical ventilator (Carina, Dräger) through a facial interface (Fitlife Respironics, Philips). A PEEP level between 5 and 10 cmH2O, minimal pressure-support level of 5 cm H2O targeting a tidal volume around 6 to 8 ml/kg and at the same FiO2 applied during the spontaneous breathing trial.<br>Device: High-flow nasal cannula<br>* High flow nasal cannula will be provided through a commercial device (AIRVO2 + Optiflow nasal cannula, Fisher & Paykel), at 50 LPM and at the same FiO2 applied during the spontaneous breathing trial.<br>|
| Experimental: Sequence B: High flow nasal cannula - Non-invasive ventilation<br>Once participants are extubated they will receive one hour of high flow nasal cannula followed by one hour of Non-invasive ventilation | Device: Non-invasive ventilation (NIV)<br>* Non-invasive ventilation will be provided through a mechanical ventilator (Carina, Dräger) through a facial interface (Fitlife Respironics, Philips). A PEEP level between 5 and 10 cmH2O, minimal pressure-support level of 5 cm H2O targeting a tidal volume around 6 to 8 ml/kg and at the same FiO2 applied during the spontaneous breathing trial.<br>Device: High-flow nasal cannula<br>* High flow nasal cannula will be provided through a commercial device (AIRVO2 + Optiflow nasal cannula, Fisher & Paykel), at 50 LPM and at the same FiO2 applied during the spontaneous breathing trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure time-product (PTP) per minute | Pressure time-product (PTP) per minute (cmH2O x s/min) | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| Esophageal pressure swings (ΔPes) | Esophageal pressure swings (ΔPes) defined as the absolute differences between end-expiratory and end-inspiratory Pes | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| End-expiratory lung impedance (EELI) | End-expiratory lung impedance (EELI)assessed with Electric impedance tomography | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure time-product per breath | Pressure time-product per breath (cmH2O x s). PTP will be assessed through an esophageal Neurovent catheter. | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| Peak electric activity of the diaphragm (EAdi) | Peak electric activity of the diaphragm (EAdi) EAdi will be measured in uV through a Neurovent catheter connected to a Servo-i ventilator | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| Neuroventilatory efficiency | Neuroventilatory efficiency is a parameter derived from the EAdi signal and the ventilation | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| Diaphragmatic neuromuscular coupling | Diaphragmatic neuromuscular coupling Pdi/EAdi | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| Global inhomogeneity index | Index derived from EIT and calculated from the sum of the impedance changes of each pixel with respect to its median (in absolute values), divided by the sum of the impedance values of each pixel | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula ] | 
| PaO2 / FiO2 ratio | Parameter of oxygen exchange calculated as the ratio of PaO2 / FiO2 | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 
| PaCO2 | Arterial partial pressure of CO2 (PaCO2) Parameter of alveolar ventilation | 60 minutes after starting Non-invasive ventilation or high flow nasal cannula | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-flow nasal cannula, Noninvasive ventilation