High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission

doi:10.1007/s12630-020-01740-2

Comparative Study

. 2020 Sep;67(9):1217-1248.

doi: 10.1007/s12630-020-01740-2. Epub 2020 Jun 15.

High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission

Arnav Agarwal¹, John Basmaji², Fiona Muttalib³, David Granton⁴, Dipayan Chaudhuri⁵, Devin Chetan^{6

7}, Malini Hu⁴, Shannon M Fernando^{8

9}, Kimia Honarmand^{2

10}, Layla Bakaa¹¹, Sonia Brar¹², Bram Rochwerg^{4

5

13}, Neill K Adhikari^{14

15}, Francois Lamontagne^{16

17}, Srinivas Murthy¹⁸, David S C Hui^{19

20}, Charles Gomersall²¹, Samira Mubareka^{22

23}, Janet V Diaz^{24

25}, Karen E A Burns^{26

27

28}, Rachel Couban^{13

29}, Quazi Ibrahim¹³, Gordon H Guyatt¹³, Per O Vandvik³⁰

Affiliations

¹ Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Centre for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
⁷ Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁸ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁹ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Schulich School of Medicine and Dentistry, Department of Medicine, Western University, London, ON, Canada.
¹¹ Honours Life Sciences Program, Faculty of Science, McMaster University, Hamilton, ON, Canada.
¹² School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA.
¹³ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
¹⁴ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁵ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Université de Sherbrooke, Sherbrooke, Canada.
¹⁷ Centre de recherche du CHU de Sherbrooke, Sherbrooke, QC, Canada.
¹⁸ BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁹ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
²⁰ Stanley Ho, Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
²¹ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
²² Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
²⁴ Pacific Medical Center, San Francisco, CA, USA.
²⁵ World Health Organization, Geneva, Switzerland.
²⁶ Unity Health Toronto - St. Michael's Hospital, Toronto, ON, Canada.
²⁷ University of Toronto, Toronto, ON, Canada.
²⁸ Li Ka Shing Knowledge Institute, Toronto, ON, Canada.
²⁹ Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
³⁰ MAGIC Evidence Ecosystem Foundation, Oslo, Norway. per.vandvik@gmail.com.

PMID: 32542464
PMCID: PMC7294988
DOI: 10.1007/s12630-020-01740-2

Comparative Study

High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission

Arnav Agarwal et al. Can J Anaesth. 2020 Sep.

. 2020 Sep;67(9):1217-1248.

doi: 10.1007/s12630-020-01740-2. Epub 2020 Jun 15.

Authors

Affiliations

¹ Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Centre for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
⁷ Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁸ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁹ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Schulich School of Medicine and Dentistry, Department of Medicine, Western University, London, ON, Canada.
¹¹ Honours Life Sciences Program, Faculty of Science, McMaster University, Hamilton, ON, Canada.
¹² School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA.
¹³ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
¹⁴ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁵ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Université de Sherbrooke, Sherbrooke, Canada.
¹⁷ Centre de recherche du CHU de Sherbrooke, Sherbrooke, QC, Canada.
¹⁸ BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁹ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
²⁰ Stanley Ho, Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
²¹ Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
²² Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
²⁴ Pacific Medical Center, San Francisco, CA, USA.
²⁵ World Health Organization, Geneva, Switzerland.
²⁶ Unity Health Toronto - St. Michael's Hospital, Toronto, ON, Canada.
²⁷ University of Toronto, Toronto, ON, Canada.
²⁸ Li Ka Shing Knowledge Institute, Toronto, ON, Canada.
²⁹ Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
³⁰ MAGIC Evidence Ecosystem Foundation, Oslo, Norway. per.vandvik@gmail.com.

PMID: 32542464
PMCID: PMC7294988
DOI: 10.1007/s12630-020-01740-2

Abstract
in English, French

Purpose: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products.

Source: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology.

Principal findings: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density.

Conclusions: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l’Organisation mondiale de la santé pour guider l’utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d’aérosols, et de transmission associée d’éléments viraux (compte rendu 2).

Source: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d’études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d’insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d’études évaluant la dispersion de gouttelettes, la génération d’aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l’extraction des données et l’évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE.

Constatations principales: Aucune étude éligible n’incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l’intensification de l’oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d’insuffisance respiratoire. Les résultats n’ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l’unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d’aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l’effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n’aient rapporté aucune augmentation associée concernant la dispersion d’aérosols, l’une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d’aérosols élevée plus grandes.

Conclusion: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l’escalade des traitements par rapport à l’oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d’insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.

Keywords: COVID-19; SARS-CoV-2; aerosols; high-flow nasal cannula; respiratory failure.

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Figures

**Fig. 1**
PRISMA flow diagram for systematic review 1 on efficacy and safety of HFNC in acute hypoxemic respiratory failure. SR = systematic reviews; RCT = randomized-controlled trial

**Fig. 2**
Need for invasive ventilation forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula; RoB = risk of bias

**Fig. 3**
Escalation of therapy forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula; RoB = risk of bias

**Fig. 4**
Mortality forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula

**Fig. 5**
Intensive care unit length of stay forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula

**Fig. 6**
Hospital length of stay forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula

**Fig. 7**
Patient-reported dyspnea forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula

**Fig. 8**
Patient-reported comfort forest plot for review on HFNC for acute hypoxemic respiratory failure. CI = confidence interval; HFNC = high-flow nasal cannula

**Fig. 9**
PRISMA flow diagram for systematic review 2 on aerosol generation associated with HFNC. SR = systematic reviews; RCT = randomized-controlled trial

See this image and copyright information in PMC

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[1] Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed

[2] Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed

[3] World Health Organization. Rolling updates on coronavirus disease (COVID-19). Available from URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-a... (accessed May 2020).

[4] World Health Organization. Rolling updates on coronavirus disease (COVID-19). Available from URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-a... (accessed May 2020).

[5] John Hopkins University of Medicine Coronavirus Resource Centre. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at John Hopkins University (JHU). Available from URL: https://coronavirus.jhu.edu/map.html (accessed May 2020).

[6] John Hopkins University of Medicine Coronavirus Resource Centre. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at John Hopkins University (JHU). Available from URL: https://coronavirus.jhu.edu/map.html (accessed May 2020).

[7] 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; DOI: 10.1001/jama.2020.2648. - PubMed

[8] 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; DOI: 10.1001/jama.2020.2648. - PubMed

[9] Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. The epidemiological characteristics of an outbreak of novel coronavirus diseases (COVID-19) in China (Chinese) Zhonghua Liu Xing Bing Xue Za Zhi. 2019;2020(41):145–151. - PubMed

[10] Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for Disease Control and Prevention. The epidemiological characteristics of an outbreak of novel coronavirus diseases (COVID-19) in China (Chinese) Zhonghua Liu Xing Bing Xue Za Zhi. 2019;2020(41):145–151. - PubMed

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High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission

Affiliations

High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its risks of aerosolization, dispersion, and infection transmission

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Affiliations

Abstract
in English, French

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Abstract in English, French

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