Therapy With High-flow Oxygen by Nasal Cannula vs Noninvasive Ventilation in Patients With Acute Hypoxemic Respiratory Failure: a Crossover Physiologic Study
Therapy With High-flow Oxygen by Nasal Cannula vs Noninvasive Ventilation in Patients With Acute Hypoxemic Respiratory Failure: a Crossover Physiologic Study
Background and rationale: A large multicenter randomized controlled trial demonstrated that
 in patients with hypoxemic non-hypercapnic respiratory failure treatment with nasal high flow
 oxygen (NHF) resulted in a reduction of the endotracheal intubation rate (38%) compared with
 noninvasive ventilation (NIV) delivered by facemask (50%) or with conventional oxygen therapy
 (47%), although the difference was not statistically significant. These results could be
 potentially explained by the physiological benefits provided by the NHF. However, one of the
 surprising findings of this study was that patients randomized to the facemask NIV group had
 a similar or even poorer outcome than oxygen alone. Interestingly, an observational study
 showed that in patients receiving facemask NIV for acute hypoxemia delivered tidal volumes
 were higher than expected (8.1-11.1 ml/kg predicted body weight), suggesting that NIV could
 potentially cause ventilator-induced lung injury resulting in worsening respiratory failure.

 We, therefore, plan a crossover physiologic study investigating the hypothesis that compared
 with NIV the treatment with NHF of patients with acute hypoxemic non-hypercapnic respiratory
 failure results in a more homogeneous distribution of tidal volume, and hence less
 ventilator-induced lung injury, as measured by electrical impedance tomography (EIT).

 Methods: This physiologic study will enroll 20 patients from the ICU at Toronto General
 Hospital in one year. Adult patients with acute hypoxemic non cardiogenic respiratory failure
 and PaO2:FiO2 ≤ 300 mmHg, respiratory rate > 25 breaths/minute, PaCO2 ≤ 45 mmHg and absence
 of clinical history of underlying chronic respiratory failure will be eligible. Patients that
 received invasive mechanical ventilation for > 48 hours in the same hospital admission,
 requiring immediate intubation, with hemodynamic instability (systolic arterial pressure < 90
 mmHg after optimal fluid therapy), with Glasgow Coma Scale < 12, or contraindications to
 noninvasive ventilation and tracheostomy, will be excluded. After baseline assessment while
 receiving oxygen through facemask or nasal prongs, patients will receive in randomly assigned
 order NHF for 20 minutes and NIV for 20 minutes, in a crossover manner. EIT recordings,
 diaphragm ultrasound, and collection of blood samples for arterial blood gases will be
 performed at the end of each phase.

 Data analysis: The primary endpoint is the comparison of the EIT intra-tidal ventilation
 index between treatment with NHF and NIV. As secondary endpoints, we will determine whether
 NHF, in comparison to NIV, provides respiratory support with lower global inhomogeneity index
 (EIT), lower tidal volumes, reduces respiratory muscle effort (respiratory rate and
 diaphragmatic ultrasound), and improves gas exchange (oxygen saturation, PaO2:FiO2, PaCO2,
 RR).
Inclusion Criteria:

 1. Hypoxemia defined by a ratio of the partial pressure of arterial oxygen to the
 fraction of inspired oxygen (PaO2:FiO2) ≤ 300 while the patient is breathing oxygen
 through NHF for at least 15 minutes;

 2. Respiratory rate > 25 breaths/minute;

 3. Partial pressure of arterial carbon dioxide (PaCO2) ≤ 45 mmHg;

 4. Absence of clinical history of underlying chronic respiratory failure.

 Exclusion Criteria:

 1. Lack of consent;

 2. Age < 18 years;

 3. Invasive mechanical ventilation for > 48 hours in the same hospital admission

 4. Immediate need for intubation;

 5. Previous inclusion in the present study;

 6. Systolic arterial pressure < 90 mmHg after optimal fluid therapy;

 7. Cardiogenic pulmonary edema;

 8. Glasgow Coma Scale < 12;

 9. Imminent death;

 10. Contraindications to noninvasive ventilation;

 11. Tracheostomy.