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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 Translated title: Les canules nasales à haut débit pour le traitement de l’insuffisance respiratoire hypoxémique aiguë chez les patients atteints de la COVID-19: comptes rendus systématiques de l’efficacité et des risques d’aérosolisation, de dispersion et de transmission de l’infection

      review-article
      , MD 1 , , MD 2 , , MD 3 , , MD 4 , , MD 5 , , MD 6 , 7 , , BSc 4 , , MD 8 , 9 , , MD 2 , 10 , , OSSD 11 , , MD 12 , , MD 4 , 5 , 13 , , MD 14 , 15 , , MD 16 , 17 , , MD 18 , , MD 19 , 20 , , MD 21 , , MD 22 , 23 , , MD 24 , 25 , , MD 26 , 27 , 28 , , MISt 13 , 29 , , MSc 13 , , MD 13 , , MD 30 ,
      Canadian Journal of Anaesthesia
      Springer International Publishing
      respiratory failure, COVID-19, SARS-CoV-2, high-flow nasal cannula, aerosols

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          Abstract

          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.

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          Most cited references62

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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              The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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                Author and article information

                Contributors
                per.vandvik@gmail.com
                Journal
                Can J Anaesth
                Can J Anaesth
                Canadian Journal of Anaesthesia
                Springer International Publishing (Cham )
                0832-610X
                1496-8975
                15 June 2020
                : 1-32
                Affiliations
                [1 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Medicine, , University of Toronto, ; Toronto, ON Canada
                [2 ]GRID grid.39381.30, ISNI 0000 0004 1936 8884, Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, , Western University, ; London, ON Canada
                [3 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Centre for Global Child Health, , Hospital for Sick Children, ; Toronto, ON Canada
                [4 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Michael G. DeGroote School of Medicine, , McMaster University, ; Hamilton, ON Canada
                [5 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Department of Medicine, , McMaster University, ; Hamilton, ON Canada
                [6 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Pediatrics, , University of Toronto, ; Toronto, ON Canada
                [7 ]GRID grid.42327.30, ISNI 0000 0004 0473 9646, Division of Cardiology, Labatt Family Heart Centre, , The Hospital for Sick Children, ; Toronto, ON Canada
                [8 ]GRID grid.28046.38, ISNI 0000 0001 2182 2255, Division of Critical Care, Department of Medicine, , University of Ottawa, ; Ottawa, ON Canada
                [9 ]GRID grid.28046.38, ISNI 0000 0001 2182 2255, Department of Emergency Medicine, , University of Ottawa, ; Ottawa, ON Canada
                [10 ]GRID grid.39381.30, ISNI 0000 0004 1936 8884, Schulich School of Medicine and Dentistry, Department of Medicine, , Western University, ; London, ON Canada
                [11 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Honours Life Sciences Program, Faculty of Science, , McMaster University, ; Hamilton, ON Canada
                [12 ]GRID grid.273335.3, ISNI 0000 0004 1936 9887, School of Medicine and Biomedical Sciences, , University of Buffalo, ; Buffalo, NY USA
                [13 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Department of Health Research Methods, Evidence and Impact, , McMaster University, ; Hamilton, ON Canada
                [14 ]GRID grid.413104.3, ISNI 0000 0000 9743 1587, Department of Critical Care Medicine, , Sunnybrook Health Sciences Centre, ; Toronto, ON Canada
                [15 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Interdepartmental Division of Critical Care Medicine, , University of Toronto, ; Toronto, ON Canada
                [16 ]GRID grid.86715.3d, ISNI 0000 0000 9064 6198, Université de Sherbrooke, ; Sherbrooke, Canada
                [17 ]Centre de recherche du CHU de Sherbrooke, Sherbrooke, QC Canada
                [18 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, BC Children’s Hospital, , University of British Columbia, ; Vancouver, BC Canada
                [19 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Medicine and Therapeutics, , The Chinese University of Hong Kong, ; Shatin, Hong Kong, SAR China
                [20 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Stanley Ho, Center for Emerging Infectious Diseases, , The Chinese University of Hong Kong, ; Shatin, Hong Kong, SAR China
                [21 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Anaesthesia and Intensive Care, , The Chinese University of Hong Kong, ; Hong Kong, China
                [22 ]GRID grid.413104.3, ISNI 0000 0000 9743 1587, Division of Infectious Diseases, , Sunnybrook Health Sciences Centre, ; Toronto, ON Canada
                [23 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Laboratory Medicine and Pathobiology, , University of Toronto, ; Toronto, ON Canada
                [24 ]GRID grid.17866.3e, ISNI 0000000098234542, Pacific Medical Center, ; San Francisco, CA USA
                [25 ]GRID grid.3575.4, ISNI 0000000121633745, World Health Organization, ; Geneva, Switzerland
                [26 ]GRID grid.415502.7, Unity Health Toronto – St. Michael’s Hospital, ; Toronto, ON Canada
                [27 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, University of Toronto, ; Toronto, ON Canada
                [28 ]GRID grid.415502.7, Li Ka Shing Knowledge Institute, ; Toronto, ON Canada
                [29 ]GRID grid.25073.33, ISNI 0000 0004 1936 8227, Michael G. DeGroote Institute for Pain Research and Care, , McMaster University, ; Hamilton, ON Canada
                [30 ]MAGIC Evidence Ecosystem Foundation, Oslo, Norway
                Author information
                http://orcid.org/0000-0001-8958-2710
                Article
                1740
                10.1007/s12630-020-01740-2
                7294988
                32542464
                627bad28-253a-4793-82d3-470e9527a2eb
                © Canadian Anesthesiologists' Society 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 14 May 2020
                : 20 May 2020
                : 20 May 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004423, World Health Organization;
                Categories
                Review Article/Brief Review

                Anesthesiology & Pain management
                respiratory failure,covid-19,sars-cov-2,high-flow nasal cannula,aerosols

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