Supplemental oxygen therapy is one of the more commonly prescribed interventions used by physicians when caring for hypoxic patients acutely. This supplementation often takes the form of the low-flow nasal cannula (LFNC). However, there are limitations to this supplemental oxygen intervention. A traditional nasal cannula can only effectively provide only up to 4 to 6 liters per minute of supplemental oxygen. This equates to a FiO2 of approximately 0.37 to 0.45. Above this number, nasal mucosal irritation occurs with the drying of the passages, and there is, therefore, an increased potential for bleeding with prolonged use. In low-flow nasal cannula therapy, FiO2 delivery is directly tied to flow rate. For increased FiO2, the rate must be increased. The low-flow nasal cannula is an open system of supplementation with high levels of leaking air around the oxygen source. As such, the efficacy of treatment for the low-flow nasal cannula is limited. High-flow nasal cannula (HFNC) therapy is an oxygen supply system capable of delivering up to 100% humidified and heated oxygen at a flow rate of up to 60 liters per minute. All settings are controlled independently allowing for greater confidence in the delivery of supplemental oxygen as well as better outcomes when used. In addition to greater control over the delivery of FiO2, there are several benefits to using a high-flow nasal cannula. The physiological mechanism of action and uses for high-flow nasal cannula are explored here.
Basic components include a flow generator providing gas flow rates up to 60 liters per minute, an air-oxygen blender that achieves escalation of FIO2 from 21% to 100% irrespective of flow rates, and a humidifier that saturates the gas mixture at temperature of 31 to 37 C. To minimize condensation, the heated humidified gas is delivered via heated tubings through a wide-bore nasal prong.
Currently, there are 5 physiologic mechanisms that are believed to be responsible for the efficacy of high-flow nasal cannula. These include:
Physiological dead space accounts for approximately one-third of the tidal volume of breathing. This allows for the accumulation of CO2 and a decrease in available oxygen (O2) for diffusion when ventilation is not effective in cycling inspired air with retained air within dead spaces. The high flow rates involved in high-flow nasal cannula delivers volumes of air over what a patient ventilates physiologically, which increases ventilation and allows for displacement of excess CO2 with excess O2. This allows for an increased PAO2 creating a greater oxygen diffusion gradient and potentially improving patient oxygenation.
High-flow nasal cannula accomplishes a reduction of nasopharyngeal airway resistance leading to improved ventilation and oxygenation through the application of a positive pressure environment. The resistance of an airway follows the Hagen–Poiseuille law and is calculated as:
Where l equals the length of the airway, n equals the dynamic viscosity of air, and r equals the radius of the airway. Physiologically, the nasopharynx is a dynamic environment that allows for expansion and constriction of the airway radius. By creating a positive pressure environment, high-flow nasal cannula presses from the interior of the nasopharynx outwards. This dilates the radius of the nasopharyngeal airways and dramatically reduces the resistance to airway flow, thus increasing ventilation and oxygenation potential.
There are several physiologic studies that showed improvement in respiratory mechanics secondary to the above-stated hypothesis by decreasing respiratory rate and increasing tidal volume.
In addition to providing positive pressure support to the nasopharynx, high-flow nasal cannula creates a positive end-expiratory pressure to the lower airways. This effect acts similarly to continuous positive airway pressure support in that it applies a splinting force to keep alveolar airways from collapsing under increased surface tensile stresses during exhalation. Additionally, this allows for improved alveolar recruitment, increasing the effective available surface area within the lungs for gaseous diffusion both to and from the blood. It is important to note, however, that patients must have their mouth closed to gain the maximum benefit of PEEP from high flow nasal cannula therapy. The approximate magnitude of PEEP generated with a closed mouth is about 1 cm of water pressure for 10 liters flow. There is a resultant increase in end-expiratory volume with an increase in PEEP. One of the challenges and potential pitfalls of this hypothesis is that it is difficult for a patient to keep their mouth closed when they are in respiratory distress.
Humidification and warming of inspired air are extremely important in creating an oxygenation system that is effective. Primarily, this is due to the human factor of comfort. Traditional low-flow nasal cannula blows cool, dry air directly into the nasal passages. This leads to drying of the mucosa, irritation, epistaxis, and cracking of the tissue barriers, which is uncomfortable and leads to poor compliance to therapy. Many high-flow nasal cannula systems are designed with inline warming and humidification systems that provide appropriately humidified and body temperature air that is non-irritating to the mucosa increasing patient comfort (31 to 37 C). Increased comfort leads to improved compliance and therefore better outcomes of therapy.
Like many other medical interventions, there are limitations and drawbacks to the high-flow nasal cannula. One of the primary drawbacks is the expense for care relative to low flow nasal cannula, increased complexity and training to initiate care, decreased mobility, a risk for ineffective sealing of the passageways leading to leaking of air and loss of the positive airway pressure effect, a potential to delay intubation, and the potential to inappropriately delay of end-of-life decisions (Spoletini et al. 2015). Furthermore, potential risk factors to noninvasive ventilation apply to a limited extent in the use of high-flow nasal cannula as well. That includes patients with alteration of consciousness, facial injury, excessive secretion with the risk of aspiration, and hemodynamic instability.
High Flow nasal cannula has many clinical applications. Some of the potential areas of clinical application where there is evolving evidence is listed below:
1.Acute Hypoxemic Respiratory Failure
2.Post Surgical Respiratory Failure
3. Acute Heart Failure /Pulmonary edema
4.Hypercapnic Respiratory Failure, COPD
5.Pre & Post extubation Oxygenation
6.Obstructive Sleep Apnea
7. Use in the emergency department
8. Do Not Intubate the patient
Acute hypoxemic respiratory failure (AHRF) occurs due to intrapulmonary shunting of blood because of airspace collapse or filling. It is usually refractory to supplemental oxygen. This occurs when there is an increase in alveolar-capillary hydrostatic pressure, increased alveolar-capillary permeability, blood due to hemorrhage, and/or fluid because of an inflammatory condition such as pneumonia. As previously discussed, high-flow nasal cannula therapy provides PEEP. The FLORALI trial  found that although high-flow nasal cannula did not reduce the rate of intubation among immunocompetent patients with non-hypercapnic hypoxic respiratory failure, patients who received high-flow nasal cannula therapy experienced reduced mortality, both in the intensive care unit (ICU) and at 90-days. The results also depicted an increase in ventilator-free days, degree of comfort, reduced dyspnea severity, and a decreased respiratory rate. No significant adverse effects link to high flow nasal cannula were noticed.
The study was underpowered for the primary outcome of intubation rate and was not replicated by two subsequent randomized controlled trials, although both showed (Stephen et al. and Maggiore et al.) high-flow nasal cannula to be equally efficient as non-invasive ventilation (NIV) in avoiding intubation and reducing mortality.
Physiologically, the ability to independently control FIO2 and oxygen flow in NIV and high-flow nasal cannula renders a clear advantage over regular oxygen therapy in patients with acute hypoxic respiratory failure, prone to hypercapnia. High-flow nasal cannula certainly provides a more comfortable alternative in patients who struggle with tolerating an NIV modality. Finally, the adverse effect on the logistics of patient location on NIV, nursing, and respiratory therapy workload needs to be accounted for.
Pre-oxygenating a patient before intubation is essential. High-flow nasal cannula therapy can provide this in an alert awake patient by achieving a high-flow rate and very high amounts of FiO2, thus increasing the amount of PO2. This gives more time for the process of intubation before desaturation happens. Historically, a non-rebreather mask (NRM) has been used to do this. However, Miguel-Mantanes et al. (2015) found that high-flow nasal cannula therapy significantly improves oxygenation during intubation as compared to a nonrebreather mask (NRM). While one retrospective analysis found that NIV such as BiPAP yields similar results to HFNC in relation to outcomes, patient compliance decreases significantly (Besnier, Emmanuel et al. 2016). This suggests that high-flow nasal cannula oxygen therapy is superior to both NRM and NIV in the pre-intubation period.
Oxygenation is also important post-extubation. Arman et al. (2017) found that while there was no significant difference in post-extubation oxygen saturation between low-flow nasal cannula and high-flow nasal cannula oxygen therapy in the ICU, there was a difference in heart rate, and respiratory rate, suggesting that low-flow nasal cannula required an increased quantity of both of these in order to achieve the same oxygen saturation. Post-extubation after surgery also necessitates oxygen therapy. Youfeng et al. (2018) completed a meta-analysis that concluded that high-flow nasal cannula could reduce the need for respiratory support compared with the low-flow nasal cannula in cardiac surgical patients. Hernandez and colleagues published 2 seminal papers in JAMA regarding the use of high flow nasal cannula in high and low-risk post-extubation patients and found that high flow nasal cannula was superior to standard care in low-risk patient post-extubation and non-inferior to non- invasive mechanical ventilation in high-risk patients post-extubation.  Furthermore in high-risk patient combining noninvasive mechanical ventilation to high flow nasal cannula was superior to all other modalities 
Immunocompromised patients carry increased mortality when undergoing endotracheal intubation. This is largely due to the increased risk of infection in these patients. The HIGH trial , performed in immunocompromised patients, did not show a significant decrease in 28-day mortality or reintubation rates in patients admitted with acute hypoxic respiratory failure when comparing high flow nasal cannula to standard oxygen therapy. No significant adverse effect was attributed to the high flow nasal cannula. A review and meta-analysis by Hui-BinHuang et al. (2018) explored high-flow nasal cannula therapy in immunocompromised patients with acute respiratory failure. The results suggest that compared to both low-flow nasal cannula and NIV, high-flow nasal cannula therapy might significantly reduce both mortality and intubation rate in the immunocompromised.
The emergency department is the first stop for most patients who are admitted to the hospital. Acute dyspnea and hypoxemia are 2 of the most common reasons for emergency department visits. Nuttapol et al. (2015) completed a prospective randomized comparative study to ascertain whether high-flow nasal cannula therapy is superior to conventional oxygen therapy in the emergency department. They found that high-flow nasal cannula therapy improves dyspnea and comfort in subjects presenting to the emergency department for dyspnea and/or hypoxemia.
According to the National Center for Health Statistics, 51,811 people died from pneumonia, and 544,000 visited the emergency room (ER) for pneumonia as the primary discharge diagnosis in 2015. Pneumonia is also a common cause of ARHF which was previously discussed. Omote et al. (2018) found that high-flow nasal cannula therapy improved 30-day survival in patients with acute respiratory failure due to interstitial pneumonia as compared to NIV.
All patients with chronic obstructive pulmonary disease (COPD) will all eventually need supplemental oxygen, provided they do not the first die from another cause. COPD exacerbations are also a common reason for the hospital admission. Many patients with COPD benefit from NIV in the acute setting. However, a large limitation of NIV is the low level of patient compliance and comfort. High-flow nasal cannula therapy provides the benefit of PEEP and increased oxygen saturation that NIV supplies but increases patient comfort and compliance. In addition, Dzira et al. (2017) discovered that in GOLD stage III and IV COPD patients, high-flow nasal cannula at flow rates greater than 30 L per minute decreased the respiratory rate, inspiratory time to total breath time ratio, and diaphragmatic work of breathing compared to NIV.
High-flow nasal cannula therapy is a relatively new treatment, and not everyone is familiar with the equipment. Educational sessions should be held for nurses, respiratory therapist and other physicians before the treatment is introduced in the hospital. A collaborative interprofessional team comprising of a respiratory therapist, the clinical or critical care nurse, and a medical provider can greatly improve patient outcomes when undergoing high-flow nasal cannula therapy. The bedside nurse can assist the medical team by monitor the patient's vital signs and respiratory effort while on high-flow therapy to ensure there is no risk of impending respiratory compromise. The respiratory therapist can titrate the flow and oxygen percentage to meet the patient's needs and decrease the risk of over oxygenation or barotrauma. Communicating the efficacy of high-flow nasal cannula with the medical provider, or the need for a higher level of respiratory support when needed, the nurses and respiratory therapist can enhance healthcare outcomes by notification of the medical team leading to timely adjustments for the patient. [Level 5]
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