COVID-19 Related Respiratory Failure: A Non-Invasive Approach

No Comments

Exploring a controversial procedure in treating pandemic.



Novel coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can precipitate a spectrum of respiratory compromise from mild illness to severe respiratory failure. [1,2]

The use of high flow nasal cannula (HFNC) or non-invasive positive pressure ventilation (NIV) in the care of these patients is controversial for a few reasons: the increased risk of aerosolization and potential exposure of healthcare workers, [3,4] the scarcity of data to support an optimal mode of treatment and the concern for patient self-induced lung injury. [5]

Care of these patients, including the choice of non-invasive support and the decision on when to intubate in the emergency department, depends on several factors: available resources, clinical trajectory and knowledge of both short- and long-term benefits and risks. This review focuses on relevant pre-COVID-19 evidence and current expert guidelines on the use of simple oxygen, HFNC and NIV in COVID-19.


High flow nasal cannula

In COVID-19, conventional oxygen devices (i.e. nasal cannula, face masks, etc.) remain the first line treatment for hypoxemia to target an oxygen saturation 90-96%. [6] If intubation is not immediately indicated and conventional oxygen fails to maintain an oxygen saturation of > 90% or if increased respiratory effort persists, HFNC is the recommended next step. HFNC is recommended over NIV in the Surviving Sepsis Campaign and National Institutes of Health COVID-19 guidelines. [6,7]

HFNC has been used successfully in other forms of pneumonia and acute respiratory distress syndrome (ARDS) 8,9 and may reduce the need for intubation when compared to conventional oxygen. [10–13]

The benefit of HFNC over conventional oxygen devices is from the flow of up to 60 L/min. Respiratory effort is decreased through nasopharyngeal dead space washout, reliably delivers a high fraction of inspired oxygen (FiO2), generates low levels of positive end expiratory pressure (PEEP), and improves comfort with warmth and humidification. [14]


HFNC in the ED was reviewed in a prior issue of EP Monthly. [15] While HFNC might increase the risk of viral transmission through aerosolization, studies have not shown an increased risk over standard oxygen devices. [16]

If HFNC is used in COVID-19 a surgical mask covering the face along with airborne precautions for staff is recommended. [16–18] Awake self-proning has the potential to increase oxygenation and may be trialed with HFNC, but the long term benefits are unclear. [19–22]  As with any patient with respiratory failure, close monitoring for deterioration is necessary as a delay in intubation is associated with worse outcomes. [23]

Figure 1. An initial approach to respiratory failure in COVID-19

NIV in COVID19.figure 1

Non-invasive ventilation

NIV for respiratory failure in chronic obstructive pulmonary disease (COPD) and cardiogenic pulmonary edema decrease both intubation and mortality rates.[24–26] The benefit of NIV in ARDS, pneumonia and other forms of acute hypoxemic respiratory failure remains controversial and COVID-19 specific evidence remains limited.

One retrospective study suggests that NIV use in severe hypoxemic respiratory failure (i.e. PaO2:FiO2 ratio <150) from ARDS is associated with a higher ICU mortality rate (36.2%) than those that were placed on invasive mechanical ventilation (24.7%).[27]  

In a 2019 retrospective study in ARDS, NIV success was associated with a survival benefit, while NIV failure did not show an increased mortality when compared to invasive ventilation, suggesting a trial of NIV is safe.[28] A recent meta-analysis in patients with hypoxemic respiratory failure, prior to COVID-19, found a decreased rate of intubation with HFNC and NIV when compared to standard oxygen therapy.[13]

Helmet and facemask NIV were associated with a lower risk of death, but the association of facemask NIV with lower mortality was no longer statistically significant with more severe hypoxemia (PaO2: FiO2 ratio ≤200). Overall, higher NIV failure rates have been demonstrated in patients with pneumonia, cirrhosis, sepsis, severe hypoxemia and persistent large tidal volumes (e.g. >9.5 mL/kg). [13,28,29]

One patient population that may benefit from NIV are the immunosuppressed with hypoxemic respiratory failure as early NIV use has been shown to improve mortality and decrease intubation rates in these patients.[30]  NIV may also be used, if permitted, in those whose goals of care do not include intubation.

While NIV has the potential to improve alveolar recruitment and oxygenation, it may increase the risk of patient self-inflicted lung injury (PSILI). PSILI is the theory that lung injury can be self-generated from large spontaneous tidal volumes and large changes in transpulmonary pressure from an increased respiratory drive.

The application of NIV with an added inspiratory positive pressure may potentiate this lung injury — with the negative effects seen long after they leave the ED. [5,31] Another important consideration is the aerosolization of viral particles and staff exposure with NIV. [3,4,32,33] Use of NIV in COVID-19 is subject to local infection prevention guidelines and ideally should be conducted in a negative pressure environment with adequate staff protective equipment.

Initial Approach

In patients with hypoxic respiratory failure from COVID-19 who do not improve with conventional oxygen therapy, HFNC is recommended. NIV may be trialed cautiously in those patients with less severe hypoxemia (e.g. PaO2:FiO2 ratios >150-200) or in those who are immunosuppressed. Severe hypoxemic failure, pneumonia and persistent large tidal volumes are associated with NIV failure.

There are no specific criteria for intubation in COVID-19, instead the decision to intubate relies on patient trajectory, response to therapy, and clinical judgement at the bedside. However, if the patient shows ongoing signs of respiratory failure (e.g. high respiratory rate, accessory muscle use, worsening hypoxemia, etc.) or is rapidly deteriorating despite optimized HFNC or NIV, then intubation with a lung protective, low tidal volume ventilation strategy should be initiated.[6]


  1. Guan W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
  2. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
  3. It Y, Zh X, Kk T, et al. Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;44(8):1017-1025. doi:10.1086/512819
  4. Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review. PLOS ONE. 2012;7(4):e35797. doi:10.1371/journal.pone.0035797
  5. Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2016;195(4):438-442. doi:10.1164/rccm.201605-1081CP
  6. Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020;46(5):854-887. doi:10.1007/s00134-020-06022-5
  7. What’s new | Coronavirus Disease COVID-19. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at Accessed 6/9/2020. Accessed June 9, 2020.
  8. Frat J-P, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196. doi:10.1056/NEJMoa1503326
  9. Messika J, Ben Ahmed K, Gaudry S, et al. Use of High-Flow Nasal Cannula Oxygen Therapy in Subjects With ARDS: A 1-Year Observational Study. Respir Care. 2015;60(2):162-169. doi:10.4187/respcare.03423
  10. Ni Y-N, Luo J, Yu H, Liu D, Liang B-M, Liang Z-A. The effect of high-flow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation. A systematic review and meta-analysis. Am J Emerg Med. 2018;36(2):226-233. doi:10.1016/j.ajem.2017.07.083
  11. Ou X, Hua Y, Liu J, Gong C, Zhao W. Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials. CMAJ Can Med Assoc J J Assoc Medicale Can. 2017;189(7):E260-E267. doi:10.1503/cmaj.160570
  12. Rochwerg B, Granton D, Wang DX, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019;45(5):563-572. doi:10.1007/s00134-019-05590-5
  13. Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. Published online June 4, 2020. doi:10.1001/jama.2020.9524
  14. Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard J-D. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. doi:10.4187/respcare.01575
  15. Lentz, Skyler, Roginski, Matthew. A Better Way to Treat Hypoxia. Published 2018. Accessed June 7, 2020.
  16. Li J, Fink JB, Ehrmann S. High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion. Eur Respir J. 2020;55(5). doi:10.1183/13993003.00892-2020
  17. Organization WH. Clinical management of COVID-19: interim guidance, 27 May 2020. Published online 2020. Accessed June 9, 2020.
  18. Leonard S, Atwood CW, Walsh BK, et al. Preliminary Findings on Control of Dispersion of Aerosols and Droplets During High-Velocity Nasal Insufflation Therapy Using a Simple Surgical Mask: Implications for the High-Flow Nasal Cannula. Chest. Published online April 2, 2020. doi:10.1016/j.chest.2020.03.043
  19. Elharrar X, Trigui Y, Dols A-M, et al. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA. Published online May 15, 2020. doi:10.1001/jama.2020.8255
  20. Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020;24. doi:10.1186/s13054-020-2738-5
  21. Xu Q, Wang T, Qin X, Jie Y, Zha L, Lu W. Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: a case series. Crit Care. 2020;24(1):250. doi:10.1186/s13054-020-02991-7
  22. Sartini C, Tresoldi M, Scarpellini P, et al. Respiratory Parameters in Patients With COVID-19 After Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit. JAMA. 2020;323(22):2338-2340. doi:10.1001/jama.2020.7861
  23. Kang BJ, Koh Y, Lim C-M, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015;41(4):623-632. doi:10.1007/s00134-015-3693-5
  24. 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 Syst Rev. 2017;7:CD004104. doi:10.1002/14651858.CD004104.pub4
  25. Berbenetz N, Wang Y, Brown J, et al. Non‐invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev. 2019;(4). doi:10.1002/14651858.CD005351.pub4
  26. Masip J, Betbesé AJ, Páez J, et al. Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial. The Lancet. 2000;356(9248):2126-2132. doi:10.1016/S0140-6736(00)03492-9
  27. Bellani G, Laffey JG, Pham T, et al. Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study. Am J Respir Crit Care Med. 2017;195(1):67-77. doi:10.1164/rccm.201606-1306OC
  28. Taha A, Larumbe-Zabala E, Abugroun A, Mohammedzein A, Naguib MT, Patel M. Outcomes of Noninvasive Positive Pressure Ventilation in Acute Respiratory Distress Syndrome and Their Predictors: A National Cohort. Crit Care Res Pract. 2019;2019:8106145. doi:10.1155/2019/8106145
  29. Carteaux G, Millán-Guilarte T, De Prost N, et al. Failure of Noninvasive Ventilation for De Novo Acute Hypoxemic Respiratory Failure: Role of Tidal Volume*. Crit Care Med. 2016;44(2):282-290. doi:10.1097/CCM.0000000000001379
  30. Hilbert G, Gruson D, Vargas F, et al. Noninvasive Ventilation in Immunosuppressed Patients with Pulmonary Infiltrates, Fever, and Acute Respiratory Failure. N Engl J Med. 2001;344(7):481-487. doi:10.1056/NEJM200102153440703
  31. Grieco DL, Menga LS, Eleuteri D, Antonelli M. Patient self-inflicted lung injury: implications for acute hypoxemic respiratory failure and ARDS patients on non-invasive support. Minerva Anestesiol. 2019;85(9). doi:10.23736/S0375-9393.19.13418-9
  32. Tarabini Fraticelli A, Lellouche F, L’Her E, Taillé S, Mancebo J, Brochard L. Physiological effects of different interfaces during noninvasive ventilation for acute respiratory failure*. Crit Care Med. 2009;37(3):939–945. doi:10.1097/CCM.0b013e31819b575f
  33. Hui DS, Chow BK, Lo T, et al. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. Eur Respir J. 2019;53(4). doi:10.1183/13993003.02339-2018


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.

Skyler Lentz, MD is the Assistant Professor of Surgery and Medicine in the Divisions of Emergency Medicine and Pulmonary Critical Care at the University of Vermont Medical Center.

Patricia Ruth Atchinson, DO, is a Critical Care Fellow at Dartmouth-Hitchcock Medical Center and an Emergency Medicine physician.

Leave A Reply