A Better Way to Treat Hypoxia

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High-flow nasal cannula is a good first option.

A 72-year-old man with a history of smoking and hypertension presents to the emergency department (ED) with cough, fever, and shortness of breath. His initial oxygen saturation is 81% on room air and the nurse places a non-rebreather (NRB) facemask to maintain an oxygen saturation of >90%. His exam is notable for fever of 102 F, moderate respiratory distress, and crackles of the bilateral lung bases. A chest x-ray confirms bilateral lower lobe opacities, and a blood gas shows hypoxemia without hypercapnia. You are considering intubating him because you have maximized the amount of oxygen you can deliver.

What is your next step for respiratory support of this patient with community-acquired pneumonia? Should you keep him on a non-rebreather mask, try non-invasive positive pressure ventilation, or initiate high flow nasal cannula?



In patients with oxygen needs greater than what a simple nasal cannula (0.5-6 L/min) can offer, oxygenation with a high-flow nasal cannula (HFNC) has many advantages. The HFNC can deliver a continuous flow of gas between 20 and 60 L/min and offers many physiologic advantages that other oxygen delivery systems do not.[1,2]

HFNC is not cranking up the standard ED delivery system to a max of 12 L/min. As seen in figure 1, HFNC requires specific devices with large bore nasal cannulas, (e.g., OptiFlow ™), which blend compressed medical air and oxygen, and can deliver a continuous flow of 20-60 L/min. HFNC devices typically require respiratory therapists or specially trained nurses for set-up, but once set-up in the ED, emergency physicians will need to manage HFNC titration (see Using HFNC in the ED section below).

A recent randomized control trial suggests HFNC decreases mortality as compared to non-invasive positive pressure ventilation (NIPPV) and simple oxygen delivery devices in hypoxemic patients admitted to ICUs.3 If resources allow, HFNC can be a first line therapy in patients with hypoxemic respiratory failure not from cardiogenic pulmonary edema and without concomitant hypercapnia.[1]



HFNC washes out nasopharyngeal dead space, improves oxygenation, decreases the work of breathing and respiratory rate, generates a low level of positive airway pressure, and provides heated and humidified gas to promote secretion clearance. The HFNC can deliver a continuous flow of gas between 20 and 60 L/min and offers many physiologic advantages that other oxygen delivery systems do not. The high flow rate makes breathing more efficient because it washes out the dead space. Dead space does not participate in gas exchange and contains a high fraction of carbon dioxide and low fraction of oxygen that is normally re-breathed. When a patient is in distress, the wash out of dead space makes breathing more efficient because it significantly decreases the amount of re-breathed carbon dioxide and acts as a continuous reservoir of new gas. This ultimately decreases the respiratory rate and work of breathing.[1,2]

While HFNC can deliver high rates of continuous oxygen flow, it does not provide a titratable pressure like NIPPV. HFNC can deliver low level positive pressure to the upper airways in the range of 2-5 cm H2O. The actual pressure depends on the flow rate, patient’s mouth being open or closed (higher with mouth closed), and phase of the respiratory cycle (higher pressures during exhalation).[4,5] Even low levels of upper airway pressure can increase the functional residual capacity (FRC) and lung recruitment.[6]

HFNC is better at oxygen delivery than the standard non-rebreather oxygen mask, venti-mask, and simple low flow nasal cannula. The distinct advantages are the flow and titratable FiO2 are not as dependent on the patient’s work of breathing to deliver a consistent and higher concentration of oxygen.[4,7] To understand why this is, we need to explore inspiratory flow and minute ventilation.

Inspiratory flow is the rate of gas entering the lungs during inspiration. Distressed and rapid breathing makes gas enter the lungs at a faster rate and thus a higher inspiratory flow. Patients in distress often have a high inspiratory flow rate that can range from 30 L/min to 100 L/min.[8] Minute ventilation is the amount of gas entering the lungs over a minute and is tidal volume multiplied by the respiratory frequency.


For patients in distress, a high inspiratory flow rate is paired with a high minute ventilation because they have large tidal volumes multiple times per minute. The optimal respiratory support device should be able to accommodate a patient in distress who has a high inspiratory flow and minute ventilation. For example, when you are reading this article, you are most likely breathing 500 mL tidal volumes over 1 second and
approximately 16 times per minute. This means you have an inspiratory flow rate of 30 L/ min (500 mL over 1 second) during each breath and a minute ventilation of 8 L/min. Now, imagine a patient in respiratory distress taking 1000 mL tidal volumes over the same 1 second, approximately 30 times per minute. This equates to a much higher inspiratory flow (60 L/min) than at rest and a higher minute ventilation (30 L/min).

As you can see, the inspiratory flow and the minute ventilation of a patient in respiratory distress is greater than the 15 L/min that a non-rebreather mask (NRB) can deliver. This means that ambient room air is being inspired along with the 100% oxygen from the mask. The fraction of oxygen mixed with room air that is reaching your patient’s alveoli is dependent on the NRB flow rate, inspiratory flow, and minute ventilation. The high flow rates of up to 60 L/ min from HFNC can in many instances match the inspiratory flow of patients in distress, leading to better and more titratable oxygen delivery to the patient. In other words, the FiO2 you set on the high-flow device is close to what is actually being delivered to the patient because less ambient air is being mixed into each breath.[4,7]

Patients are able to tolerate the high flow rates from a HFNC because of heating and humidification. Prior to reaching the patient’s nose, the air can be humidified to 100% and warmed to body temperature. This both improves patient comfort and preserves mucociliary function. It improves secretion management and can reduce re-intubation related to upper airway obstruction.[9] It can also decrease the amount of energy the patient expends heating and humidifying inspired air.


HFNC works best for patients with hypoxemic respiratory failure—but not from cardiogenic pulmonary edema and not in the presence of concomitant hypercapnia. The most frequent indication for its use in the ED is pneumonia. HFNC is an exciting and relatively new modality for respiratory support in adults. Consequently, the research is continuously changing and always being updated. The FLORALI trial in 2015 randomized hypoxemic patients with PaO2:FiO2 ratios of < 300, mostly from pneumonia, to receive oxygen through a facemask, HFNC or NIPPV. While the primary outcome of patients requiring endotracheal intubation after randomization was no different among the treatment modalities, the group treated with HFNC had a decrease in 90-day mortality.[3] The results of this trial support the use of HFNC over NIPPV and simple oxygen devices in patients with hypoxic failure, mostly from pneumonia.

Other research focused on HFNC is being studied in PEEP responsive processes such as acute cardiogenic pulmonary edema because of the small increase in PEEP.[10] However, HFNC is not able to achieve the levels of titratable PEEP that can be delivered by NIPPV, so HFNC is not currently indicated for acute cardiogenic pulmonary edema or hypercapnic states.


There are only two variables an emergency physician needs to adjust when using HFNC: flow and FiO2. Starting with flow, commercially available devices can deliver up to 60 L/min. Start the patient on 30-35 L/min and adjust the flow based on the patient’s level of respiratory distress. For example, if your patient has continued tachypnea or distress after 10-15 minutes of therapy at 30L/min, increase the flow to 40-45 L/min to provide more support. The general principle is the more distress your patient is in, the more flow is needed.

Regarding oxygenation, adjust the FiO2 between 21-100% to obtain desired oxygen saturation. Reassess the patient frequently, and don’t delay intubation if required. If the patient has continued tachypnea, hypoxemia, and increased work of breathing after maximizing the flow and FiO2, the patient needs to be intubated. Beware of the patient on 60 L/min of flow and 100% FiO2 who remains in respiratory distress!

This patient is failing despite a tremendous amount of support from the high flow device and will need intubation. Anticipate desaturation during an intubation attempt. HFNC is effective at pre-oxygenation and apneic oxygenation during an intubation attempt. Leave the HFNC cannula in place throughout induction and laryngoscopy, as the continuous high flow promotes apneic gas exchange. One before-and-after study suggests fewer desaturations with pre-oxygenation from HFNC as compared to NRB in mild to moderately hypoxic ICU patients, but another study suggested no difference in desaturations when used in those with more severe hypoxemia.[12,13]

If the patient is already being treated with a HFNC, our practice is to leave it in place with maximal flow and FiO2 during induction and intubation. Similarly, in a patient with a difficult airway who requires an awake fiberoptic intubation, consider initiation of HFNC while preparing to intubate. For an urgent orotracheal intubation with a patient sitting upright, this approach offers pre-oxygenation while the proceduralist readies equipment and applies topical anesthetic to the mouth and glottis. The nasal cannula does not obstruct the proceduralist and offers respiratory support during the awake intubation.


In the patient with a terminal illness who presents emergently with respiratory distress, HFNC can be a helpful adjunct in managing the patient’s symptoms while clarifying further goals of care. It offers the benefit of being able to speak and eat and is better tolerated than NIPPV. If the patient does not wish to be intubated, HFNC can assist with comfort and work of breathing along with other palliative therapies.[14]


The patient in the case was transitioned from NRB to HFNC 50 L/min and 80% FiO2. His oxygenation and work of breathing improved over his ED course, and he was admitted to the ICU. He spent the next 3 days on HFNC in the ICU on flow rates of > 40 L/min and FiO2 ranging from 70-90% but he never required intubation. High-flow nasal cannula should be considered a first line therapy in all patients with hypoxemic respiratory failure not from cardiogenic pulmonary edema and without concomitant hypercapnia.

HFNC offers many advantages over low flow nasal cannula and NRB that include washout of dead space leading to reduction in the work of breathing, better titration of oxygen, heated and humidified gas to promote secretion clearance, and a low level of positive pressure. This therapy may ultimately decrease mortality in patients with pneumonia as compared to NIPPV and low flow oxygen devices. When initiating therapy, start the patient at 30-35 L/min of flow and titrate the flow rate and FiO2 to work of breathing and oxygen saturation. Reach for HFNC on your next shift.


  1. Hugo Lenglet et al. “Humidified High Flow Nasal Oxygen During Respiratory Failure in the Emergency Department: Feasibility and Efficacy.” Respir Care 2012;57(11):1873-1878.
  2. Jens Bräunlich et al. “Effects of Nasal High Flow on Ventilation in Volunteers, COPD and Idiopathic Pulmonary Fibrosis Patients.” Respiration 2013;85:319-325
  3. Jean-Pierre Frat et al. “High Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure.” The New England Journal of Medicine 2015;372:2185-96.
  4. E. Rithchie et al. “Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures.” Anaesth Intensive Care 2011;39:1103-110
  5. Rachel L Park and Shay P McGuiness. “Pressure Delivered by Nasal High Flow Oxygen During all Phases of the Respiratory Cycle.” Respir Care 2013; 58(10):1621:1624
  6. Jordi Riera et al. Effect of High-Flow Nasal Cannula and Body Position on End-Expiratory Lung Volume: A Cohort Study Using Electrical Impedance Tomography. Respiratory Care April 2013, 58 (4) 589-596
  7. A. B. Sim et al. “Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated.” Anaesthesia 2008;63:938-940.
  8. Nishimura, Masaji. High-flow nasal cannula oxygen therapy in adults. Journal of Intensive Care (2015) 3:15
  9. Gonzalo Hernández et al. “High-flow nasal cannula support therapy: new insights and improving performance.” Critical Care 2017;21:62
  10. Onlak Makdee et al. “High-Flow Nasal Cannula Versus Conventional Oxygen Therapy in Emergency Department Patients With Cardiogenic Pulmonary Edema: A Randomized Controlled Trial.” Ann Emerg Med. 2017;70:465-472
  11. Vital FMR, Ladeira MT, Atallah ÁN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD005351. DOI: 10.1002/14651858.CD005351.pub3
  12. Romain Miguel-Montanes et al. “Use of High-Flow Nasal Cannula Oxygen Therapy to Prevent Desaturation during Tracheal Intubation of Intensive Care Patients with Mild-to-Moderate Hypoxemia.” Crit Care Med 2015; 43:574–583
  13. Vourc’h, M., Asfar, P., Volteau, C. et al. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med (2015) 41: 1538. https://doi.org/10.1007/s00134-015-3796-z
  14. Giulia Spoletini et al. Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Applications. Chest 2015; 148(1): 253-261. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2017, Issue 7. Art. No.: CD004104. DOI: 10.1002/14651858.CD004104.pub4.



Skyler Lentz, MD, is a Critical Care Fellow and Instructor in Medicine at Dartmouth-Hitchcock Medical Center.

Matthew Roginski, MD, MPH, is an Assistant Professor of Medicine in the Sections of Emergency and Critical Care Medicine and the DHART Assistant Medical Director at Dartmouth-Hitchcock Medical Center.

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