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 Table of Contents  
Year : 2020  |  Volume : 4  |  Issue : 5  |  Page : 6-9

High-Flow Nasal Cannula for Patients with COVID-19 Acute Hypoxemic Respiratory Failure

1 College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
2 Department of Emergency Medicine and Critical Care, College of Medicine, King Saud University, Riyadh; Adult Critical Care Services, Ministry of Health, Dammam, Saudi Arabia
3 Department of Emergency and Critical Care Medicine, King Fahd Hospital of the University, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia

Date of Submission02-Sep-2020
Date of Acceptance28-Sep-2020
Date of Web Publication7-Dec-2020

Correspondence Address:
Mohammed Saeed Alshahrani
Department of Emergency and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, PO Box 40236, Dammam 31952
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sccj.sccj_42_20

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High-flow nasal cannula (HFNC) is a noninvasive oxygenation modality that delivers heated and humidified oxygen. It possesses several advantages due to the unique physiological effects on the lung and ventilation mechanics compared to other modes of oxygen therapy. The use of HFNC is tolerable, comfortable, and easy to set up. Current evidence indicates that the use of HFNC in critically ill patients with coronavirus disease 2019 (COVID-19)-acute hypoxemic respiratory failure (AHRF) is noninferior to noninvasive ventilation in the reduction of endotracheal intubation rate. Early identification of HFNC failure is vital to avoid delaying intubation. However, multiple knowledge gaps exist, and unpowered observational studies limit HFNC incorporation into strong recommendations. The low dispersion of particles demonstrates the feasibility of HFNC; yet, an appropriate setting and precautions should be maximized. Here, we review the recent evidence of HFNC implications in the management of patients with COVID-19-AHRF.

Keywords: Acute hypoxemic respiratory failure, ARDS, COVID-19, high-flow nasal cannula, noninvasive, oxygen therapy, review article

How to cite this article:
Alshaqaq HM, Al Aseri ZA, Alshahrani MS. High-Flow Nasal Cannula for Patients with COVID-19 Acute Hypoxemic Respiratory Failure. Saudi Crit Care J 2020;4, Suppl S1:6-9

How to cite this URL:
Alshaqaq HM, Al Aseri ZA, Alshahrani MS. High-Flow Nasal Cannula for Patients with COVID-19 Acute Hypoxemic Respiratory Failure. Saudi Crit Care J [serial online] 2020 [cited 2023 Feb 8];4, Suppl S1:6-9. Available from: https://www.sccj-sa.org/text.asp?2020/4/5/6/302580

  Introduction Top

On early March 2020, the World Health Organization has assessed that coronavirus disease 2019 (COVID-19) can be characterized as a pandemic and declared a public health emergency of international concerns.[1] The causative agent of this disease was attributed to a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, China. Subsequently, the outbreak has rapidly spread throughout the world.

During the early phase of the pandemic, concerns of rapid deterioration in respiratory function have led to early endotracheal intubation (ETI) and mechanical ventilation (MV) practices in patients with COVID-19-related acute hypoxemic respiratory failure (AHRF). However, a higher fatality rate was observed among invasively ventilated patients with COVID-19-AHRF.[2] This practice was also driven by the aerosolization fear that might be encountered in noninvasive oxygen therapies. Lately, reports have indicated minimal aerosol dispersion with the high-flow nasal cannula (HFNC) utilization.[3] In this article, we aim to summarize the current evidence of HFNC implications in the management of patients with COVID-19-AHRF.

  High-Flow Nasal Cannula Top

HFNC is a noninvasive oxygenation technique through which heated and humidified oxygen-rich gas is delivered at a high-flow rate through nasal prongs. This innovative modality is designed to provide oxygenated gas up to 60 L/min of supplemental oxygen with 0.21–1.0 of fraction of inspired oxygen (FiO2). In the last decade, the use of HFNC gained considerable attention as a potential alternative of respiratory support for multiple indications in critically ill patients.[4] Several mechanisms of action have led to improved clinical outcomes, which include humidification and heating, flush out of CO2 from the upper airways, and decreased work of breathing [Table 1].[5],[6],[7]
Table 1: Physiological and clinical effects of high-flow nasal cannula

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  High-Flow Nasal Cannula Utilization in Coronavirus Disease 2019-Related Acute Hypoxemia Respiratory Failure Top

An observational study by Vianello et al. reported a rate of HFNC success to be as high as 67.8% of the included patients (19/28), which was defined as no need for escalation of intervention to noninvasive ventilation (NIV) or ETI.[8] After multivariate logistic regression analysis, PaO2/FiO2 ≤100 mmHg at the intensive care unit (ICU) admission demonstrated a significant association with HFNC failure, which might be used as a possible predictive value.[8] Despite the great importance of this report, the small sample size and retrospective design possess noticeable limitations.

Another study by Wang et al. showed a 41% (seven patients) rate of HFNC failure in 17 retrospectively collected patients.[9] Subsequently, these patients required escalation of oxygen therapy, in which they were managed by NIV.[9] Only two patients underwent ETI after the failure of NIV, representing a rate of 11.8% out of the entire cohort (2/17).[9] None of the patients with PaO2/FiO2 >200 mmHg had HFNC failure compared to 63% in patients with lower PaO2/FiO2 (≤200 mmHg).[9] In addition, respiratory rate (RR) was observed to decrease significantly following 1–2 h of HFNC in patients who were in the HFNC success group.[9] Once again, the retrospective nature and small sample size constitute significant limitations. Furthermore, the management and escalation of oxygen therapy were based on treating physician discretion which indicates the lack of prespecified criteria for when and what escalation of therapy is needed.

Another retrospective study involved 109 patients who were treated by HFNC for COVID-19-AHRF.[10] HFNC success was observed in 28.4% of their cohort, in which 71.6% of patients experienced HFNC failure and needed escalation of respiratory support to ETI.[10] However, the mortality rate of the HFNC failure group was numerically lower compared to patients who were managed with immediate MV (30.8% vs. 40.2%, respectively), but it did not meet the statistical significance.[10] In this cohort, HFNC failure was significantly associated with chronic obstructive pulmonary disease, higher sequential organ failure assessment score at ICU admission, and higher white blood cell count.[10]

The authors concluded that HFNC utilization before ETI was not correlated with increased mortality compared to the group of patients with MV only (n = 97).[10] Interestingly, after adjusting for possible confounding variables, a longer time from ICU admission to ETI was not associated with increased mortality.[10] Although this finding might provide assurance to encourage the use of HFNC, prospective randomized controlled trials are needed to confirm these findings. Despite the considerable value added to the literature by this great investigation, the retrospective design and possible confounders in decision-making limit the conclusions drawn from this study.

A recent multicenter retrospective study by Xia et al. that included 43 patients has reported success with HFNC in 53.5% of patients, whereas 46.5% of patients failed HFNC.[11] Of the HFNC failure group, 30.2% of patients needed to undergo ETI and MV, and 13.9% received NIV.[11] Moreover, this investigation has identified factors that could possibly predict HFNC success including higher SpO2 at the time of admission, young patients, and female patients.[11] Male gender and low SpO2 at admission were independent predictors for HFNC failure in the multivariate regression model.[11]

In contrast, high RR and a significant reduction of rate of oxygenation (ROX) index within 3 days of HFNC treatment were associated with HFNC failure. The ROX index was proposed by Roca et al. to predict HFNC failure.[12] The ROX index is measured by the ratio of SpO2/FiO2 to RR. Roca et al. reported that ROX of ≥4.88 measured after the initiation of HFNC at 2, 6, and 12 h is consistently associated with a lower risk of HFNC failure.[12] In COVID-19, a retrospective study involved 62 patients with COVID-19-AHRF demonstrated that a ROX index measured after 4 h of HFNC initiation to be significantly associated with HFNC success and low risk of ETI.[13] This study provided a great advantage to the existing literature in identifying the cutoff of ROX index in COVID-19-AHRF; nevertheless, retrospective design implies an inherent limitation. In contrast, another study was conducted to assess the accuracy of multiple monitoring parameters in the prediction of HFNC failure in COVID-19-AHRF.[14] It showed that the diagnostic value of the ROX index was not better than RR at half an hour alone.[14] They found that RR ≥26/min was associated with a high risk of HFNC failure.[14] However, this study is limited by the small sample size and the high SpO2 (100%) seen in a third of their cohort, which has decreased the potential accuracy of the ROX index. Future large-scale validation should confirm these results.

Xia et al. reported the overall in-hospital mortality in HFNC to be approximately one-third, and it doubled in the HFNC failure group.[11] Nevertheless, lower mortality rate was observed in HFNC when compared to a group of patients (n = 13) who were immediately intubated without the trail of HFNC.[11] This study demonstrated promising evidence of HFNC success in a group of patients with COVID-AHRF; however, poor prognosis was associated with HFNC failure.[11] This indicates that, with the application of appropriate selection criteria, a significant number of patients could avoid ETI, with caution not to use HFNC in patients who have high chance of HFNC failure. Although this study added substantial value to the existing literature, several limitations exist that might affect the conclusions drawn from the results. These include the retrospective nature of the study, small sample size, possible selection bias in the recruitment processes, and lack of controlled arm with conventional oxygen therapy or NIV. [Figure 1] and [Table 2] summarize the main outcomes of HFNC use in COVID-19-AHRF.
Figure 1: Reported rates of high-flow nasal cannula success and failure in coronavirus disease 2019 acute hypoxemic respiratory failure

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Table 2: Reported outcomes associated with high-flow nasal cannula success and failure

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  High-Flow Nasal Cannula Aerosolization Safety Top

During the early surge of SARS-Cov-2, concerns of aerosol generation related to HFNC were prominent. Although it was shown that if HFNC is delivered through a tightly fitted and strapped interface to the face, the risk of exhaled air dispersion is minimal.[15] Besides, a new study demonstrated no increase in aerosol particle concentration following the use of HFNC in comparison to room air or nonhumidified modalities.[3] Furthermore, the study by Vianello et al. reported weekly negative PCR testing for COVID-19 for all health-care staff during their HFNC study period and following it for 14 days.[8] We believe that, in the good setting with the use of negative pressure rooms, high-efficiency particulate air filter, appropriate personal protective equipment, and surgical mask, HFNC is feasible with minimal risk of aerosolization.

  Conclusion Top

HFNC is an innovative technique of providing oxygenation and ventilation with several physiological and clinical benefits. Growing evidence supports the use of HFNC in AHRF as an effective modality in the early course of treatment; however, in COVID-19-AHRF, the early application of HFNC might be an effective method to avoid ETI and improve the overall outcome. Further studies are required to confirm the efficacy of the use of HFNC in critically ill patients with COVID-19-AHRF and in identifying appropriate selection criteria for patients who most likely will benefit from the use of HFNC.

  Future Research Directions Top

HFNC has been investigated in randomized controlled studies for other different causes of respiratory failure, an example of which community-acquired pneumonia, heart failure, chronic obstructive lung diseases, and other indications. However, in COVID-19-AHRF, the high quality of evidence is still scarce. Future research should focus on developing a decision tool to guide the selection of patients who might benefit of using HFNC, identifying early predictors of HFNC failure in COVID-AHRF, identifying the optimal timing of intubation after HFNC in COVID-19-AHRF, and understanding the clinical outcome of COVID-19-AHRF patients who underwent HFNC in regards to mortality and length of ICU and hospital stay.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

WHO Director-General. WHO Director-General’s Opening Remarks at the Media Briefing on COVID-19; 11 March, 2020. WHO; 2020. Available from: https://www.who.int/dg/speeches/detail/who-direc tor-general-s-opening-remarks-at-themedia-briefing-on-covid- 19---11-march-2020.  Back to cited text no. 1
Grasselli G, Greco M, Zanella A, Albano G, Antonelli M, Bellani G, et al. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med 2020:1-11. [doi: org/10.1001/jamainternmed. 2020.3539].  Back to cited text no. 2
Gaeckle NT, Lee J, Park Y, Kreykes G, Evans MD, Hogan CJ Jr. Aerosol generation from the respiratory tract with various modes of oxygen delivery. Am J Respir Crit Care Med 2020.  Back to cited text no. 3
Rochwerg B, Granton D, Wang DX, Helviz Y, Einav S, Frat JP, 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;45:563-72.  Back to cited text no. 4
Mauri T, Turrini C, Eronia N, Grasselli G, Volta CA, Bellani G, et al. Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2017;195:1207-15.  Back to cited text no. 5
L’Her E, Deye N, Lellouche F, Taille S, Demoule A, Fraticelli A, et al. Physiologic effects of noninvasive ventilation during acute lung injury. Am J Respir Crit Care Med 2005;172:1112-8.  Back to cited text no. 6
Markovitz GH, Colthurst J, Storer TW, Cooper CB. Effective inspired oxygen concentration measured via transtracheal and oral gas analysis. Respir Care 2010;55:453-9.  Back to cited text no. 7
Vianello A, Arcaro G, Molena B, Turato C, Sukthi A, Guarnieri G, et al. High-flow nasal cannula oxygen therapy to treat patients with hypoxemic acute respiratory failure consequent to SARS-CoV-2 infection. Thorax 2020.  Back to cited text no. 8
Wang K, Zhao W, Li J, Shu W, Duan J. The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China. Ann Intensive Care 2020;10:1-5.  Back to cited text no. 9
Hernandez-Romieu AC, Adelman MW, Hockstein MA, Robichaux CJ, Edwards JA, Fazio JC, et al. Timing of intubation and mortality among critically Ill coronavirus disease 2019 patients: A single-center cohort study. Crit Care Med 2020.  Back to cited text no. 10
Xia J, Zhang Y, Ni L, Chen L, Zhou C, Gao C, et al. High-flow nasal oxygen in coronavirus disease 2019 patients with acute hypoxemic respiratory failure. Crit Care Med. 2020. [doi: org/10.1097/CCM.0000000000004558].  Back to cited text no. 11
Roca O, Caralt B, Messika J, Samper M, Sztrymf B, Hernández G, et al. An index combining respiratory rate and oxygenation to predict outcome of nasal high-flow therapy. Am J Respir Crit Care Med 2019;199:1368-76.  Back to cited text no. 12
Zucman N, Mullaert J, Roux D, Roca O, Ricard JD, Contributors. Prediction of outcome of nasal high flow use during COVID-19-related acute hypoxemic respiratory failure. Intensive Care Med 2020.  Back to cited text no. 13
Blez D, Soulier A, Bonnet F, Gayat E, Garnier M. Monitoring of high-flow nasal cannula for SARS-CoV-2 severe pneumonia: Less is more, better look at respiratory rate. Intensive Care Med 2020.  Back to cited text no. 14
Hui DS, Chow BK, Lo T, Tsang OTY, Ko FW, Ng SS, et al. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. Eur Respir J 2019;53.  Back to cited text no. 15


  [Figure 1]

  [Table 1], [Table 2]


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