Physiologic Effects of High-flow Nasal Cannula Versus Standard Oxygen Therapy Postextubation in Critically Ill Patients

Study Overview
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Brief Summary
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High-flow nasal cannula (HFNC) is a rather novel system to provide oxygen therapy, which provides flows up to 60 liters/minute (LPM) of heated and humidified gas through nasal prongs. HFNC is increasingly being used in patients with acute respiratory failure. In healthy volunteers and in patients with acute respiratory failure it has been shown to induce several effects beyond those expected for a standard oxygen therapy, such as increased carbon dioxide (CO2) clearance and positive airway pressure. One of the potential indications for HFNC is to facilitate weaning from mechanical ventilation and extubation. As weaning failure is one of the most complex challenges in mechanically ventilated patients, the use of HFNC after extubation, in order to prevent reintubation, has been evaluated in some clinical trials, with promising results. However, the role of HFNC postextubation is still controversial, and information regarding its effects on the pathophysiologic mechanisms of weaning failure is lacking. The goal of this proposal is to compare the acute physiologic effects of postextubation HFNC versus standard oxygen therapy, in critically ill patients, on relevant mechanisms related to weaning failure: work of breathing, lung function, systemic hemodynamics. This will be a randomized crossover study which 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 HFNC and one hour of standard oxygen therapy, 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 High-flow Nasal Cannula Versus Standard Oxygen Therapy in Critically Ill Patients: a Physiologic Randomized Crossover Study

Conditions
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Ventilator Weaning

Intervention / Treatment
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* Device: High flow nasal cannula
* Device: Standard oxygen therapy


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 Potential for weaning as determined in routine daily screening (precipitating cause leading to MV in resolution, adequate oxygenation (PaO2/FiO2 ≥150 mmHg with FiO2 ≤0.4 and PEEP ≤8 cm H2O), arterial pH >7.25, hemodynamic stability (no vasopressors or Noradrenaline ≤0.1 mcg/kg/min), temperature <38°C, presence of inspiratory effort and appropriate spontaneous cough, and the patient is not receiving sedatives and is awake and able to follow simple commands) Decision to perform a spontaneous breathing trial by the attending physician Exclusion Criteria: Patients ventilated for decompensated chronic obstructive pulmonary disease Contraindications to HFNC, which include abnormalities or surgery of the face, nose, or airway that preclude an appropriate-fitting nasal cannula. 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) Presence of 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A: High flow nasal cannula - Standard oxygen therapy<br>Once participants are extubated they will receive one hour of high flow nasal cannula followed by one hour of standard oxygen therapy. | 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>Device: Standard oxygen therapy<br>* Standard oxygen therapy will be provided through a Venturi mask and O2 flow will be adjusted to keep the same FiO2 applied during the spontaneous breathing trial.<br>|
| Experimental: Sequence B: Standard oxygen therapy - High flow nasal cannula<br>Once participants are extubated they will receive one hour of standard oxygen therapy followed by one hour of high flow nasal cannula. | 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>Device: Standard oxygen therapy<br>* Standard oxygen therapy will be provided through a Venturi mask and O2 flow will be adjusted to keep 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 (cmH2O x s/min) | PTPmin will be assessed through an esophageal Neurovent catheter. | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 
| Delta end-expiratory lung index (EELI) | Delta EELI will be obtained from electric impedance tomography (EIT) and measured relative to the tidal volume. | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 
| Brain natriuretic peptide (BNP) plasma levels |  | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure time-product per breath (cmH2O x s) | PTP will be assessed through an esophageal Neurovent catheter. | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 
| 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 high flow nasal cannula or standard oxygen therapy | 
| Neuroventilatory efficiency | Vt / EAdi (ml / uV) | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 
| Neuromechanical efficiency | Ratio of the (Paw-PEEP) divided by EAdi during inspiratory occlusion (cmH2O / uV) | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 
| 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 high flow nasal cannula or standard oxygen therapy | 
| PaO2 / FiO2 | Parameter of oxygen exchange calculated as the ratio of PaO2 / FiO2 | 60 minutes after starting high flow nasal cannula or standard oxygen therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High flow nasal cannula