1. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure R4 김형오 Jean-Pierre Frat, M.D., Arnaud W. Thille, M.D., Ph.D., Alain Mercat, M.D., Ph.D., Christophe Girault, M.D., Ph.D., Stephanie Ragot, Pharm.D., Ph.D., Sebastien Perbet, M.D., Gwenael Prat, M.D., Thierry Boulain, M.D., Elise Morawiec, M.D., Alice Cottereau, M.D., Jerome Devaquet, M.D., Saad Nseir, M.D., Ph.D., Keyvan Razazi, M.D., Jean-Paul Mira, M.D., Ph.D., Laurent Argaud, M.D., Ph.D., Jean-Charles Chakarian, M.D., Jean-Damien Ricard, M.D., Ph.D., Xavier Wittebole, M.D., Stephanie Chevalier, M.D., Alexandre Herbland, M.D., Muriel Fartoukh, M.D., Ph.D., Jean-Michel Constantin, M.D., Ph.D., Jean-Marie Tonnelier, M.D., Marc Pierrot, M.D., Armelle Mathonnet, M.D., Gaetan Beduneau, M.D., Celine Deletage-Metreau, Ph.D., Jean-Christophe M. Richard, M.D., Ph.D., Laurent Brochard, M.D., and Rene Robert, M.D., Ph.D., for the FLORALI Study Group and the REVA Network* May 17, 2015, at NEJM.org

2. Introduction High-flow oxygen therapy –Nasal cannula –Heated / humidified oxygen delivered to the nose at high flow rates –Lowering physiological dead space by flushing expired CO2 –Lowering work of breathing Shown to result in better comfort and oxygenation than standard oxygen therapy delivered through a face mask in patients with acute respiratory failure of various origins

3. Introduction Noninvasive positive pressure ventilation –Intubation / mortality need reduction COPE AE, cardiogenic pulmonary edema –Decrease in work of breathing –Improvement in gas exchange But data on the overall effects of noninvasive ventilation with respect to the prevention of intubation and improvement in outcome are conflicting in patients with acute hypoxemic respiratory failure

4. Objective To compare High-flow oxygen therapy with noninvasive ventilation or standard oxygen therapy among patients with acute hypoxemic respiratory failure

5. Methods Patients –23 ICUs in France and Belgium –18 years old or older –Respiratory rate of more than 25 breaths/min –PaO2/FiO2 ≤ 300mmHg While patient was breathing oxygen at a flow rate of 10L/min or more for least 15 minutes –PaCO2 ≤ 45mmHg –Absence of clinical history of underlying chronic respiratory failure

6. Methods Exclusion criteria –PaCO2 > 45mmHg –Asthma / COPD acute exacerbation –Cardiogenic pulmonary edema –Severe neutropenia –Hemodynamic instability –Vasopressor usage –Glasgow Coma Scale of 12 points or less –Urgent need for endotracheal intubation –DNR

8. Methods Standard oxygen group –Nonrebreather face mask, 10L/min or more –Rate adjusted, target SpO2 92% or more –Measured by pulse oximetry –Until the patient recoverd or was intubated

9. Methods High flow oxygen group –Oxygen passed through a heated humidifier –Large-bore binasal prongs –50L/min gas flow with FiO2 1.0 at initiation –FiO2 adjusted, target SpO2 92% or more –Applied at least 2 subsequent days

10. Methods Noninvasive-ventilation group –Through a face mask –Pressure support applied in a noninvasive ventilation mode –Tidal volume 7~10mL/Kg targeted of predicted body weight –Initial PEEP 2~10cmH2O –Minimal duration of 8 hrs/d for at least 2 subsequent days

11. Methods Primary outcome –Endotracheal intubation within 28 days Hemodynamic instability Deterioration of neurologic status Signs of worsening respiratory failure –40/min ≤ RR –High respiratory muscle workload –Development of large amount of secretion –Acidosis with pH of less than 7.35 –SpO2 less than 90% for more than 5 minutes without technical dysfunction Secondary outcome –Mortality in the ICU –Mortality at 90 days –Number of ventilation free days : day 1~ day 28 –Duration of ICU stay

13. 38% 47% 50%

18. Discussion Strengths –Multicenter design and sealed randomization to the assigned strategy –Prespecified intubation criteria –Complete follow up at 90 days Limitations –Intubation rate in the overall population Low power to detect a significant between-group difference –PaO2:FiO2 ≤ 200mmHg subgroup difference significance

19. Conclusion Treatment with high flow oxygen improved the survival rate among patients with acute hypoxemic respiratory failure No difference in the primary outcome was observed with high flow oxygen therapy as compared with standard oxygen therapy or noninvasive ventilation