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High-Flow Therapie bei COVID-19-Pneumonie

Artikel

Autor: Aude Garnero, Intensivmedizinerin, Hôpital Sainte Musse, Toulon, Frankreich

Datum: 04.05.2021

Die High-Flow Therapie (HFT) ist eine nichtinvasive Form der Atemunterstützung, die die Intubationsrate und Sterblichkeit bei Patienten mit akutem hypoxämischem Atemversagen (AHRF) senken kann (1). Aufgrund von Bedenken hinsichtlich des Infektionsrisikos für das medizinische Pflegepersonal wurde anfänglich davon abgeraten, die HFT bei COVID-19-Patienten einzusetzen (2, 3).

High-Flow Therapie bei COVID-19-Pneumonie

Kernaussagen

  • Obwohl ursprünglich vom Einsatz einer High-Flow Sauerstofftherapie bei COVID-19-Patienten abgeraten wurde, hat sie sich aufgrund von hohen Sterblichkeitsraten bei maschinell beatmeten Patienten allmählich durchgesetzt.
  • Die HFT wirkte sich bei durch COVID-19-Pneumonie bedingtem AHRF positiv auf die Oxygenierung aus und Forschungsergebnisse legen nahe, dass sie die Notwendigkeit einer maschinellen Beatmung sowie deren Dauer reduzieren kann.
  • Wenn geeignete persönliche Schutzausrüstung verwendet wird und als Vorsichtsmassnahme eine Kohortierung erfolgt, kann die HFT bei COVID-19-Patienten angewendet werden, ohne dass es zu einem messbaren Anstieg an COVID-19-Infektionen beim medizinischen Pflegepersonal kommt.

Wegen der hohen Morbidität und Mortalität, die mit einer frühzeitigen invasiven maschinellen Beatmung verbunden ist (Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-54​), wird die HFT jedoch mittlerweile immer häufiger bei Patienten mit schwerem COVID-19 angewendet (Villarreal-Fernandez E, Patel R, Golamari R, Khalid M, DeWaters A, Haouzi P. A plea for avoiding systematic intubation in severely hypoxemic patients with COVID-19-associated respiratory failure. Crit Care. 2020;24(1):337. Published 2020 Jun 12. doi:10.1186/s13054-020-03063-65​). Dieser Artikel befasst sich mit den wissenschaftlichen Erkenntnissen zu den physiologischen Effekten, der Auswirkung auf die Behandlungsergebnisse, dem Kontaminationsrisiko und dem kombinierten Einsatz der Bauchlage (BL) mit der HFT bei Patienten mit AHRF aufgrund von COVID-19-Pneumonie.

Physiologische Effekte

Die physiologischen Effekte der HFT bei akutem hypoxämischem Atemversagen sind bekannt, aber es liegen keine spezifischen physiologischen Daten für die COVID-19-Pneumonie vor (Spoletini G, Alotaibi M, Blasi F, Hill NS. Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications. Chest. 2015;148(1):253-261. doi:10.1378/chest.14-28716​, Mauri T, Turrini C, Eronia N, et al. Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure. Am J Respir Crit Care Med. 2017;195(9):1207-1215. doi:10.1164/rccm.201605-0916OC7​, Ricard JD, Roca O, Lemiale V, et al. Use of nasal high flow oxygen during acute respiratory failure. Intensive Care Med. 2020;46(12):2238-2247. doi:10.1007/s00134-020-06228-78​). Die HFT verringert die Wahrscheinlichkeit, dass dem Patienten bei der Inspiration Raumluft mit zugeführt wird, und stellt so eine zuverlässigere Verabreichung hoher FiO2-Konzentrationen sicher. Die HFT erhöht das endexspiratorische Lungenvolumen und erzeugt damit einen PEEP, der für ein Recruitment der Alveolen verantwortlich ist und damit die regionale Dehnungsbelastung der Lunge reduziert. Diese Mechanismen verbessern die Oxygenierung.

Die Auswaschung des physiologischen Totraums durch das Ausspülen ausgeatmeter Luft aus den oberen Atemwegen während der Exspiration erhöht die Wirksamkeit der Beatmung. Die HFT verringert das erforderliche Minutenvolumen, um eine physiologische arterielle CO2-Konzentration zu erzielen, indem sie die Atemfrequenz und den anatomischen Totraum verringert. Dadurch bleibt die alveoläre Belüftung (Minutenvolumen minus Totraumbeatmung) stabil, während das Minutenvolumen sinkt. Die HFT verringert auch die inspiratorischen Bemühungen des Patienten und senkt die metabolische Atemarbeit. Schliesslich verbessert die HFT die Atemmechanik, d. h. die dynamische Compliance, den transpulmonalen Druck und die homogene Belüftung der Lunge, und erhöht den Patientenkomfort und die Toleranz im Vergleich zu konventionellen Sauerstoffbehandlungen.

Therapieergebnisse

Bei einer retrospektiven Beobachtungsstudie (Demoule A, Vieillard Baron A, Darmon M, et al. High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19. Am J Respir Crit Care Med. 2020;202(7):1039-1042. doi:10.1164/rccm.202005-2007LE9​) wurden die Intubationsrate und die Sterblichkeit zwischen 233 (51 %) Patienten, die eine konventionelle Sauerstofftherapie erhielten, und 146 (39 %) Patienten verglichen, die mit der HFT behandelt wurden. Die Intubationsrate war im Vergleich zu 75 % bei der Gruppe mit konventioneller Sauerstofftherapie mit 56 % bei der HFT-Gruppe signifikant geringer. Die Sterblichkeit am 28. Tag lag bei der Gruppe mit konventioneller Sauerstofftherapie bei 30 % gegenüber 21 % bei der HFT-Gruppe.

In einer multizentrischen Kohortenstudie (Mellado-Artigas R, Ferreyro BL, Angriman F, et al. High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure. Crit Care. 2021;25(1):58. Published 2021 Feb 11. doi:10.1186/s13054-021-03469-w10​) wurde die Behandlung mit der HFT mit der frühzeitigen Intubation bei 122 Patienten verglichen (61 Patienten in jeder Gruppe). Die HFT wurde mit mehr Tagen ohne Unterstützung durch das Beatmungsgerät und einem kürzeren Aufenthalt auf der Intensivstation in Verbindung gebracht. Bei der Sterblichkeit wurde kein Unterschied beobachtet. Allerdings zeigte eine Analyse, dass Patienten mit frühzeitiger Intubation höhere SOFA- und APACHE II-Scores aufwiesen und damit zu Studienbeginn kränker waren.

Diese beiden Studien legen nahe, dass COVID-19-Patienten von der HFT profitieren können, da sie die Notwendigkeit und die Dauer einer maschinellen Beatmung senkt sowie den Aufenthalt auf der Intensivstation verkürzt, ohne dass sich das auf die Sterblichkeit im Krankenhaus auswirkt. Allerdings gibt es keine randomisierten kontrollierten Studien, die die Therapieergebnisse von HFT-Patienten mit denen mit konventioneller Sauerstofftherapie oder frühzeitiger Intubation vergleichen.

Drei Beobachtungsstudien liefern Daten zu mit HFT behandelten COVID-19-Patienten. Die Intubationsraten lagen zwischen 36 % (Patel M, Gangemi A, Marron R, et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir Res. 2020;7(1):e000650. doi:10.1136/bmjresp-2020-00065011​) und 63 % (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;46(10):1924-1926. doi:10.1007/s00134-020-06177-112​) und die Zeit bis zur Intubation betrug zwischen 10 Stunden (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;46(10):1924-1926. doi:10.1007/s00134-020-06177-112​) und 2 Tagen (Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine. 2020;28:100570. doi:10.1016/j.eclinm.2020.10057013​). Faktoren, die mit einem erfolgreichen Therapieergebnis bei der HFT in Verbindung gebracht wurden, waren eine Behandlung mit Steroiden, niedrige CRP- und D-Dimer-Werte, Hypertonie und Rauchen (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;46(10):1924-1926. doi:10.1007/s00134-020-06177-112​, Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine. 2020;28:100570. doi:10.1016/j.eclinm.2020.10057013​).

Monitoring

Daten belegen, dass Patienten, bei denen die HFT erfolgreich war, zu Beginn der HFT eine niedrigere Atemfrequenz aufwiesen als die Patienten, die später intubiert werden mussten (Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine. 2020;28:100570. doi:10.1016/j.eclinm.2020.10057013​, Xu J, Yang X, Huang C, et al. A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure. Front Med (Lausanne). 2020;7:607821. Published 2020 Dec 8. doi:10.3389/fmed.2020.60782114​, 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;46(11):2094-2095. doi:10.1007/s00134-020-06199-915​). Bei einer monozentrischen prospektiven Beobachtungsstudie lag der beste Cut-Off-Wert bei 26 Atemzyklen pro Minute nach 30 Minuten HFT (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;46(11):2094-2095. doi:10.1007/s00134-020-06199-915​).

Der ROX-Index (Respiratory rate-OXygenation, Atemfrequenz-Oxygenierung) errechnet sich aus den Atemvariablen, mit denen das Atemversagen beurteilt wird, und kann daher verwendet werden, um die Notwendigkeit einer invasiven Beatmung zu prognostizieren. Er stellt das Verhältnis von SpO2/FiO2 zur Atemfrequenz dar. Bei akutem hypoxämischem Atemversagen aufgrund einer nicht durch COVID-19 bedingten Pneumonie wurden mit dem ROX-Index Patienten mit einem niedrigen Risiko für ein Versagen der HFT bei einem Cut-Off-Wert von 4,88 ermittelt, der nach 12 Stunden Behandlung mit HFT gemessen wurde (Roca O, Messika J, Caralt B, et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016;35:200-205. doi:10.1016/j.jcrc.2016.05.02216​). Bei COVID-19-Patienten zeigten fünf retrospektive Studien (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;46(10):1924-1926. doi:10.1007/s00134-020-06177-112​, Xu J, Yang X, Huang C, et al. A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure. Front Med (Lausanne). 2020;7:607821. Published 2020 Dec 8. doi:10.3389/fmed.2020.60782114​, Hu M, Zhou Q, Zheng R, et al. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med. 2020;20(1):324. Published 2020 Dec 24. doi:10.1186/s12890-020-01354-w17​, Chandel A, Patolia S, Brown AW, et al. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care. 2021;66(6):909-919. doi:10.4187/respcare.0863118​, Panadero C, Abad-Fernández A, Rio-Ramirez MT, et al. High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip Respir Med. 2020;15(1):693. Published 2020 Sep 16. doi:10.4081/mrm.2020.69319​), dass Patienten mit einem erfolgreichen Therapieergebnis einen höheren ROX-Index aufwiesen, aber der Cut-Off-Punkt für mit einem Therapieerfolg verbundene Werte zwischen 5,55 nach 6 Stunden (Hu M, Zhou Q, Zheng R, et al. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med. 2020;20(1):324. Published 2020 Dec 24. doi:10.1186/s12890-020-01354-w17​) und 3,67 nach 12 Stunden variierte (Chandel A, Patolia S, Brown AW, et al. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care. 2021;66(6):909-919. doi:10.4187/respcare.0863118​).

Kontamination

Der Grossteil der Studien zur HFT bei COVID-19 ist entweder experimentell oder wurde an gesunden Probanden durchgeführt und gibt damit nicht das echte Leben wieder. Die Weltgesundheitsorganisation gab Prüfungen in Auftrag, um die Studienergebnisse zur Verwendung der HFT zu untersuchen. Es wurden sechs Simulationsstudien und eine Crossoverstudie an Nicht-COVID-19-Patienten ausgewertet. Die HFT erhöhte das Risiko einer Aerosoldispersion im Vergleich zu einer typischen Patientenatmung mit starker Exspiration nicht. Die Aerosolproduktion und die Partikelkonzentrationen, die bei der HFT festgestellt wurden, waren mit denen bei Einsatz von Nasenprongs, Nicht-Rebreather-Masken und spontaner Atmung vergleichbar (Agarwal A, Basmaji J, Muttalib F, et al. 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. 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. Can J Anaesth. 2020;67(9):1217-1248. doi:10.1007/s12630-020-01740-220​). Die HFT mit einer OP-Maske auf dem Gesicht des Patienten könnte damit eine vernünftige Praxis sein, von der hypoxämische COVID-19-Patienten profitieren können (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):2000892. Published 2020 May 14. doi:10.1183/13993003.00892-202021​).

Die Hälfte der Abstrichproben aus der Umgebung eines COVID-19-Patienten im Isolierraum, der mit HFT und nichtinvasiver Beatmung (NIV) behandelt wurde, waren positiv. Dagegen waren alle Luftproben negativ. Lebensfähige Viren wurden auf einem Viertel der getesteten Stellen gefunden. Diese Ergebnisse zeigen, wie wichtig es ist, persönliche Schutzausrüstung zu tragen (Ahn JY, An S, Sohn Y, et al. Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy. J Hosp Infect. 2020;106(3):570-576. doi:10.1016/j.jhin.2020.08.01422​).

Die Inzidenz von COVID-19-Infektionen wurde in einem US-amerikanischen Krankenhaus vor und nach der Anwendung von HFT/NIV gemessen. Die Ergebnisse belegten, dass der Einsatz der HFT bei einem COVID-19-Patienten bei Verwendung von geeigneter persönlicher Schutzausrüstung und vorsorglicher Kohortierung nicht zu einem messbaren Anstieg der COVID-19-Infektionen beim medizinischen Pflegepersonal führte (Westafer LM, Soares WE 3rd, Salvador D, Medarametla V, Schoenfeld EM. No evidence of increasing COVID-19 in health care workers after implementation of high flow nasal cannula: A safety evaluation. Am J Emerg Med. 2021;39:158-161. doi:10.1016/j.ajem.2020.09.08623​).

HFT in Kombination mit der Bauchlage

Die BL kann bei wachen Patienten das Ventilations-Perfusions-Verhältnis verbessern und durch angemessene Sputumdrainage atelektatische Lungenareale eröffnen. Zwei beschreibende Studien meldeten Daten von COVID-19-Patienten, die mit HFT in Kombination mit BL behandelt wurden. Bei der Studie an 10 Patienten (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. Published 2020 May 24. doi:10.1186/s13054-020-02991-724​) war das PaO2/FiO2-Verhältnis nach der BL höher. Der PaCO2-Wert stieg an, blieb aber unter den physiologischen Werten (üblicherweise wird bei spontan atmenden COVID-19-Patienten Hypokapnie beobachtet). Keiner der Patienten musste intubiert werden. Bei der zweiten Studie an neun Patienten (Tu GW, Liao YX, Li QY, et al. Prone positioning in high-flow nasal cannula for COVID-19 patients with severe hypoxemia: a pilot study. Ann Transl Med. 2020;8(9):598. doi:10.21037/atm-20-300525​) wurde die BL zweimal täglich angewendet, mit einem Medianwert von 5 (3 bis 8) Anwendungen pro Proband. Der Medianwert der Behandlungsdauer betrug 2 (1 bis 4) Stunden. Der SaO2- und der PaO2-Wert stiegen nach der BL an. Der PaCO2-Wert sank in der Studie, aber die Patienten wiesen zu Beginn Hyperkapnie auf. Zwei Patienten mussten intubiert werden.

Bei einer prospektiven multizentrischen, angepassten Kohortenstudie (Ferrando C, Mellado-Artigas R, Gea A, et al. Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study. Crit Care. 2020;24(1):597. Published 2020 Oct 6. doi:10.1186/s13054-020-03314-626​) erhielten 199 Patienten HFT und 55 davon (28 %) wurden auf dem Bauch gelagert. Der Einsatz der BL als adjuvante Therapie zur HFT senkte das Intubationsrisiko nicht: 82 (41 %) Patienten mussten intubiert werden – 60 (41 %) in der HFNO-Gruppe und 22 (40 %) in der Gruppe mit HFT + BL. Die Dauer von der HFT bis zur Intubation war bei der Gruppe mit HFT + BL länger. Die BL wirkte sich nicht auf die Sterblichkeit aus. Bei der Gruppe mit HFT + BL zeigte sich eine starke Tendenz zu einer Verzögerung der Intubation um 2 Tage; die Sterblichkeit war bei beiden Gruppen ähnlich. Bei dieser Studie war die BL allerdings aufgrund medizinischer Kriterien indiziert und wurde nicht einheitlich angewendet. Die Autoren konnten nicht ermitteln, ob das klinische Personal die BL als Standardpraxis oder als Rettungsmassnahme für COVID-19-Patienten einsetzte. Die BL wurde nur bei der Analyse berücksichtigt, wenn die Dauer > 16 Stunden/Tag war, und die Ergebnisse konnten nicht auf Patienten ausgeweitet werden, die für einen kürzeren Zeitraum auf dem Bauch gelagert wurden. Das legte aber keine schlechtere Prognose bei verzögerter Intubation nahe.

Abschliessende Bemerkungen

Die HFT wirkte sich bei durch COVID-19-Pneumonie bedingtem AHRF positiv auf die Oxygenierung aus. Die Patienten, bei denen die HFT nicht erfolgreich war, wiesen eine höhere Sterblichkeitsrate auf, da sie zu Studienbeginn kränker waren. Der ROX-Index kann für die Prognose einer Intubation verwendet werden, aber der optimale Cut-Off-Wert steht noch zur Diskussion. Bei Verwendung von geeigneter persönlicher Schutzausrüstung und entsprechenden Vorsichtsmassnahmen kommt es nachweislich bei der HFT nicht zu einer erhöhten Kontamination oder Infektion des medizinischen Pflegepersonals. Der kombinierte Einsatz von HFT und BL muss noch weiter untersucht werden.

Alle Beatmungsgeräte von Hamilton Medical bieten die High-Flow Sauerstofftherapie als Standardausstattung oder als Option. Es sind keine Zusatzgeräte oder zusätzlichen Beatmungsgeräte erforderlich und die Therapie kann nach Bedarf mit der nichtinvasiven Beatmung abgewechselt werden, indem das Interface ausgetauscht oder einfach auf einen anderen Modus umgeschaltet wird. Der HAMILTON-H900 Befeuchter bietet nun auch einen speziellen Modus für die High-Flow Sauerstofftherapie mit eigenen Einstellungen, um den Einsatz der High-Flow Sauerstofftherapie bei allen Patientengruppen zu erleichtern.

 

Den vollständigen Quellenverweis finden Sie unten: (Frat JP, 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/NEJMoa15033261​, Zuo MZ, Huang YG, Ma WH, et al. Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019 [published online ahead of print, 2020 Feb 27]. Chin Med Sci J. 2020;35(2):105-109. doi:10.24920/0037242​, Brown CA 3rd, Mosier JM, Carlson JN, Gibbs MA. Pragmatic recommendations for intubating critically ill patients with suspected COVID-19. J Am Coll Emerg Physicians Open. 2020;1(2):80-84. Published 2020 Apr 13. doi:10.1002/emp2.120633​​)

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Fußnoten

Referenzen

  1. 1. Frat JP, 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
  2. 2. Zuo MZ, Huang YG, Ma WH, et al. Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019 [published online ahead of print, 2020 Feb 27]. Chin Med Sci J. 2020;35(2):105-109. doi:10.24920/003724
  3. 3. Brown CA 3rd, Mosier JM, Carlson JN, Gibbs MA. Pragmatic recommendations for intubating critically ill patients with suspected COVID-19. J Am Coll Emerg Physicians Open. 2020;1(2):80-84. Published 2020 Apr 13. doi:10.1002/emp2.12063
  4. 4. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-5
  5. 5. Villarreal-Fernandez E, Patel R, Golamari R, Khalid M, DeWaters A, Haouzi P. A plea for avoiding systematic intubation in severely hypoxemic patients with COVID-19-associated respiratory failure. Crit Care. 2020;24(1):337. Published 2020 Jun 12. doi:10.1186/s13054-020-03063-6
  6. 6. Spoletini G, Alotaibi M, Blasi F, Hill NS. Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications. Chest. 2015;148(1):253-261. doi:10.1378/chest.14-2871
  7. 7. Mauri T, Turrini C, Eronia N, et al. Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure. Am J Respir Crit Care Med. 2017;195(9):1207-1215. doi:10.1164/rccm.201605-0916OC
  8. 8. Ricard JD, Roca O, Lemiale V, et al. Use of nasal high flow oxygen during acute respiratory failure. Intensive Care Med. 2020;46(12):2238-2247. doi:10.1007/s00134-020-06228-7
  9. 9. Demoule A, Vieillard Baron A, Darmon M, et al. High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19. Am J Respir Crit Care Med. 2020;202(7):1039-1042. doi:10.1164/rccm.202005-2007LE
  10. 10. Mellado-Artigas R, Ferreyro BL, Angriman F, et al. High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure. Crit Care. 2021;25(1):58. Published 2021 Feb 11. doi:10.1186/s13054-021-03469-w
  11. 11. Patel M, Gangemi A, Marron R, et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir Res. 2020;7(1):e000650. doi:10.1136/bmjresp-2020-000650
  12. 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;46(10):1924-1926. doi:10.1007/s00134-020-06177-1
  13. 13. Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine. 2020;28:100570. doi:10.1016/j.eclinm.2020.100570
  14. 14. Xu J, Yang X, Huang C, et al. A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure. Front Med (Lausanne). 2020;7:607821. Published 2020 Dec 8. doi:10.3389/fmed.2020.607821
  15. 15. 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;46(11):2094-2095. doi:10.1007/s00134-020-06199-9
  16. 16. Roca O, Messika J, Caralt B, et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016;35:200-205. doi:10.1016/j.jcrc.2016.05.022
  17. 17. Hu M, Zhou Q, Zheng R, et al. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med. 2020;20(1):324. Published 2020 Dec 24. doi:10.1186/s12890-020-01354-w
  18. 18. Chandel A, Patolia S, Brown AW, et al. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care. 2021;66(6):909-919. doi:10.4187/respcare.08631
  19. 19. Panadero C, Abad-Fernández A, Rio-Ramirez MT, et al. High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip Respir Med. 2020;15(1):693. Published 2020 Sep 16. doi:10.4081/mrm.2020.693
  20. 20. Agarwal A, Basmaji J, Muttalib F, et al. 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. 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. Can J Anaesth. 2020;67(9):1217-1248. doi:10.1007/s12630-020-01740-2
  21. 21. 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):2000892. Published 2020 May 14. doi:10.1183/13993003.00892-2020
  22. 22. Ahn JY, An S, Sohn Y, et al. Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy. J Hosp Infect. 2020;106(3):570-576. doi:10.1016/j.jhin.2020.08.014
  23. 23. Westafer LM, Soares WE 3rd, Salvador D, Medarametla V, Schoenfeld EM. No evidence of increasing COVID-19 in health care workers after implementation of high flow nasal cannula: A safety evaluation. Am J Emerg Med. 2021;39:158-161. doi:10.1016/j.ajem.2020.09.086
  24. 24. 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. Published 2020 May 24. doi:10.1186/s13054-020-02991-7
  25. 25. Tu GW, Liao YX, Li QY, et al. Prone positioning in high-flow nasal cannula for COVID-19 patients with severe hypoxemia: a pilot study. Ann Transl Med. 2020;8(9):598. doi:10.21037/atm-20-3005
  26. 26. Ferrando C, Mellado-Artigas R, Gea A, et al. Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study. Crit Care. 2020;24(1):597. Published 2020 Oct 6. doi:10.1186/s13054-020-03314-6

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.

Frat JP, 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



BACKGROUND

Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia.

METHODS

We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28.

RESULTS

A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006).

CONCLUSIONS

In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019.

Zuo MZ, Huang YG, Ma WH, et al. Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019 [published online ahead of print, 2020 Feb 27]. Chin Med Sci J. 2020;35(2):105-109. doi:10.24920/003724

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.

Pragmatic recommendations for intubating critically ill patients with suspected COVID-19.

Brown CA 3rd, Mosier JM, Carlson JN, Gibbs MA. Pragmatic recommendations for intubating critically ill patients with suspected COVID-19. J Am Coll Emerg Physicians Open. 2020;1(2):80-84. Published 2020 Apr 13. doi:10.1002/emp2.12063

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.

Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-5



BACKGROUND

An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia.

METHODS

In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation.

FINDINGS

Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients.

INTERPRETATION

The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced.

FUNDING

None.

A plea for avoiding systematic intubation in severely hypoxemic patients with COVID-19-associated respiratory failure.

Villarreal-Fernandez E, Patel R, Golamari R, Khalid M, DeWaters A, Haouzi P. A plea for avoiding systematic intubation in severely hypoxemic patients with COVID-19-associated respiratory failure. Crit Care. 2020;24(1):337. Published 2020 Jun 12. doi:10.1186/s13054-020-03063-6

Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications.

Spoletini G, Alotaibi M, Blasi F, Hill NS. Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications. Chest. 2015;148(1):253-261. doi:10.1378/chest.14-2871

Traditionally, nasal oxygen therapy has been delivered at low flows through nasal cannulae. In recent years, nasal cannulae designed to administer heated and humidified air/oxygen mixtures at high flows (up to 60 L/min) have been gaining popularity. These high-flow nasal cannula (HFNC) systems enhance patient comfort and tolerance compared with traditional high-flow oxygenation systems, such as nasal masks and nonrebreathing systems. By delivering higher flow rates, HFNC systems are less apt than traditional oxygenation systems to permit entrainment of room air during patient inspiration. Combined with the flushing of expired air from the upper airway during expiration, these mechanisms assure more reliable delivery of high Fio2 levels. The flushing of upper airway dead space also improves ventilatory efficiency and reduces the work of breathing. HFNC also generates a positive end-expiratory pressure (PEEP), which may counterbalance auto-PEEP, further reducing ventilator work; improve oxygenation; and provide back pressure to enhance airway patency during expiration, permitting more complete emptying. HFNC has been tried for multiple indications, including secretion retention, hypoxemic respiratory failure, and cardiogenic pulmonary edema, to counterbalance auto-PEEP in patients with COPD and as prophylactic therapy or treatment of respiratory failure postsurgery and postextubation. As of yet, very few high-quality studies have been published evaluating these indications, so recommendations regarding clinical applications of HFNC remain tentative.

Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure.

Mauri T, Turrini C, Eronia N, et al. Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure. Am J Respir Crit Care Med. 2017;195(9):1207-1215. doi:10.1164/rccm.201605-0916OC



RATIONALE

High-flow nasal cannula (HFNC) improves the clinical outcomes of nonintubated patients with acute hypoxemic respiratory failure (AHRF).

OBJECTIVES

To assess the effects of HFNC on gas exchange, inspiratory effort, minute ventilation, end-expiratory lung volume, dynamic compliance, and ventilation homogeneity in patients with AHRF.

METHODS

This was a prospective randomized crossover study in nonintubated patients with AHRF with PaO2/setFiO2 less than or equal to 300 mm Hg admitted to the intensive care unit. We randomly applied HFNC set at 40 L/min compared with a standard nonocclusive facial mask at the same clinically set FiO2 (20 min/step).

MEASUREMENTS AND MAIN RESULTS

Toward the end of each phase, we measured arterial blood gases, inspiratory effort, and work of breathing by esophageal pressure swings (ΔPes) and pressure time product, and we estimated changes in lung volumes and ventilation homogeneity by electrical impedance tomography. We enrolled 15 patients aged 60 ± 14 years old with PaO2/setFiO2 130 ± 35 mm Hg. Seven (47%) had bilateral lung infiltrates. Compared with the facial mask, HFNC significantly improved oxygenation (P < 0.001) and lowered respiratory rate (P < 0.01), ΔPes (P < 0.01), and pressure time product (P < 0.001). During HFNC, minute ventilation was reduced (P < 0.001) at constant arterial CO2 tension and pH (P = 0.27 and P = 0.23, respectively); end-expiratory lung volume increased (P < 0.001), and tidal volume did not change (P = 0.44); the ratio of tidal volume to ΔPes (an estimate of dynamic lung compliance) increased (P < 0.05); finally, ventilation distribution was more homogeneous (P < 0.01).

CONCLUSIONS

In patients with AHRF, HFNC exerts multiple physiologic effects including less inspiratory effort and improved lung volume and compliance. These benefits might underlie the clinical efficacy of HFNC.

Use of nasal high flow oxygen during acute respiratory failure.

Ricard JD, Roca O, Lemiale V, et al. Use of nasal high flow oxygen during acute respiratory failure. Intensive Care Med. 2020;46(12):2238-2247. doi:10.1007/s00134-020-06228-7

Nasal high flow (NHF) has gained popularity among intensivists to manage patients with acute respiratory failure. An important literature has accompanied this evolution. In this review, an international panel of experts assessed potential benefits of NHF in different areas of acute respiratory failure management. Analyses of the physiological effects of NHF indicate flow-dependent improvement in various respiratory function parameters. These beneficial effects allow some patients with severe acute hypoxemic respiratory failure to avoid intubation and improve their outcome. They require close monitoring to not delay intubation. Such a delay may worsen outcome. The ROX index may help clinicians decide when to intubate. In immunocompromised patients, NHF reduces the need for intubation but does not impact mortality. Beneficial physiological effects of NHF have also been reported in patients with chronic respiratory failure, suggesting a possible indication in acute hypercapnic respiratory failure. When intubation is required, NHF can be used to pre-oxygenate patients either alone or in combination with non-invasive ventilation (NIV). Similarly, NHF reduces reintubation alone in low-risk patients and in combination with NIV in high-risk patients. NHF may be used in the emergency department in patients who would not be offered intubation and can be better tolerated than NIV.

High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19.

Demoule A, Vieillard Baron A, Darmon M, et al. High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19. Am J Respir Crit Care Med. 2020;202(7):1039-1042. doi:10.1164/rccm.202005-2007LE

High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure.

Mellado-Artigas R, Ferreyro BL, Angriman F, et al. High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure. Crit Care. 2021;25(1):58. Published 2021 Feb 11. doi:10.1186/s13054-021-03469-w



PURPOSE

Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19.

METHODS

We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding.

RESULTS

Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: - 8.2 days; 95% CI - 12.7 to - 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64).

CONCLUSIONS

The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.

Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure.

Patel M, Gangemi A, Marron R, et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir Res. 2020;7(1):e000650. doi:10.1136/bmjresp-2020-000650

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

Prediction of outcome of nasal high flow use during COVID-19-related acute hypoxemic respiratory failure.

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;46(10):1924-1926. doi:10.1007/s00134-020-06177-1

The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study.

Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine. 2020;28:100570. doi:10.1016/j.eclinm.2020.100570



BACKGROUND

The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied.

METHODS

We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO.

FINDINGS

The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [PaO2/FiO2 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%).

INTERPRETATION

In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure.

Xu J, Yang X, Huang C, et al. A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure. Front Med (Lausanne). 2020;7:607821. Published 2020 Dec 8. doi:10.3389/fmed.2020.607821

Background: High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic. Methods: Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals. Results: Among the training cohort, the median duration of HFNC therapy was 6 (range, 3-11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08-3.44; p = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96-9.20; p < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 109/L (OR, 3.04; 95% CI, 1.46-6.35; p = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79-6.23; p < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, p < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71-0.92). Conclusions: Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.

Monitoring of high-flow nasal cannula for SARS-CoV-2 severe pneumonia: less is more, better look at respiratory rate.

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;46(11):2094-2095. doi:10.1007/s00134-020-06199-9

Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index.

Roca O, Messika J, Caralt B, et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index. J Crit Care. 2016;35:200-205. doi:10.1016/j.jcrc.2016.05.022



PURPOSE

The purpose of the study is to describe early predictors and to develop a prediction tool that accurately identifies the need for mechanical ventilation (MV) in pneumonia patients with hypoxemic acute respiratory failure (ARF) treated with high-flow nasal cannula (HFNC).

MATERIALS AND METHODS

This is a 4-year prospective observational 2-center cohort study including patients with severe pneumonia treated with HFNC. High-flow nasal cannula failure was defined as need for MV. ROX index was defined as the ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate.

RESULTS

One hundred fifty-seven patients were included, of whom 44 (28.0%) eventually required MV (HFNC failure). After 12 hours of HFNC treatment, the ROX index demonstrated the best prediction accuracy (area under the receiver operating characteristic curve 0.74 [95% confidence interval, 0.64-0.84]; P<.002). The best cutoff point for the ROX index was estimated to be 4.88. In the Cox proportional hazards model, a ROX index greater than or equal to 4.88 measured after 12 hours of HFNC was significantly associated with a lower risk for MV (hazard ratio, 0.273 [95% confidence interval, 0.121-0.618]; P=.002), even after adjusting for potential confounding.

CONCLUSIONS

In patients with ARF and pneumonia, the ROX index can identify patients at low risk for HFNC failure in whom therapy can be continued after 12 hours.

Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study.

Hu M, Zhou Q, Zheng R, et al. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med. 2020;20(1):324. Published 2020 Dec 24. doi:10.1186/s12890-020-01354-w



BACKGROUND

It had been shown that High-flow nasal cannula (HFNC) is an effective initial support strategy for patients with acute respiratory failure. However, the efficacy of HFNC for patients with COVID-19 has not been established. This study was performed to assess the efficacy of HFNC for patients with COVID-19 and describe early predictors of HFNC treatment success in order to develop a prediction tool that accurately identifies the need for upgrade respiratory support therapy.

METHODS

We retrospectively reviewed the medical records of patients with COVID-19 treated by HFNC in respiratory wards of 2 hospitals in Wuhan between 1 January and 1 March 2020. Overall clinical outcomes, the success rate of HFNC strategy and related respiratory variables were evaluated.

RESULTS

A total of 105 patients were analyzed. Of these, 65 patients (61.9%) showed improved oxygenation and were successfully withdrawn from HFNC. The PaO2/FiO2 ratio, SpO2/FiO2 ratio and ROX index (SpO2/FiO2*RR) at 6h, 12h and 24h of HFNC initiation were closely related to the prognosis. The ROX index after 6h of HFNC initiation (AUROC, 0.798) had good predictive capacity for outcomes of HFNC. In the multivariate logistic regression analysis, young age, gender of female, and lower SOFA score all have predictive value, while a ROX index greater than 5.55 at 6 h after initiation was significantly associated with HFNC success (OR, 17.821; 95% CI, 3.741-84.903 p<0.001).

CONCLUSIONS

Our study indicated that HFNC was an effective way of respiratory support in the treatment of COVID-19 patients. The ROX index after 6h after initiating HFNC had good predictive capacity for HFNC outcomes.

High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success.

Chandel A, Patolia S, Brown AW, et al. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care. 2021;66(6):909-919. doi:10.4187/respcare.08631



BACKGROUND

Optimal timing of mechanical ventilation in COVID-19 is uncertain. We sought to evaluate outcomes of delayed intubation and examine the ROX index (ie, [[Formula: see text]]/breathing frequency) to predict weaning from high-flow nasal cannula (HFNC) in patients with COVID-19.

METHODS

We performed a multicenter, retrospective, observational cohort study of subjects with respiratory failure due to COVID-19 and managed with HFNC. The ROX index was applied to predict HFNC success. Subjects that failed HFNC were divided into early HFNC failure (≤ 48 h of HFNC therapy prior to mechanical ventilation) and late failure (> 48 h). Standard statistical comparisons and regression analyses were used to compare overall hospital mortality and secondary end points, including time-specific mortality, need for extracorporeal membrane oxygenation, and ICU length of stay between early and late failure groups.

RESULTS

272 subjects with COVID-19 were managed with HFNC. One hundred sixty-four (60.3%) were successfully weaned from HFNC, and 111 (67.7%) of those weaned were managed solely in non-ICU settings. ROX index >3.0 at 2, 6, and 12 hours after initiation of HFNC was 85.3% sensitive for identifying subsequent HFNC success. One hundred eight subjects were intubated for failure of HFNC (61 early failures and 47 late failures). Mortality after HFNC failure was high (45.4%). There was no statistical difference in hospital mortality (39.3% vs 53.2%, P = .18) or any of the secondary end points between early and late HFNC failure groups. This remained true even when adjusted for covariates.

CONCLUSIONS

In this retrospective review, HFNC was a viable strategy and mechanical ventilation was unecessary in the majority of subjects. In the minority that progressed to mechanical ventilation, duration of HFNC did not differentiate subjects with worse clinical outcomes. The ROX index was sensitive for the identification of subjects successfully weaned from HFNC. Prospective studies in COVID-19 are warranted to confirm these findings and to optimize patient selection for use of HFNC in this disease.

High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.

Panadero C, Abad-Fernández A, Rio-Ramirez MT, et al. High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip Respir Med. 2020;15(1):693. Published 2020 Sep 16. doi:10.4081/mrm.2020.693



INTRODUCTION

High-flow nasal cannula oxygen therapy (HFNC) has been shown to be a useful therapy in the treatment of patients with Acute Respiratory Distress Syndrome (ARDS), but its efficacy is still unknown in patients with COVID-19. Our objective is to describe its utility as therapy for the treatment of ARDS caused by SARS-CoV-2.

METHODS

A retrospective, observational study was performed at a single centre, evaluating patients with ARDS secondary to COVID-19 treated with HFNC. The main outcome was the intubation rate at day 30, which defined failure of therapy. We also analysed the role of the ROX index to predict the need for intubation.

RESULTS

In the study period, 196 patients with bilateral pneumonia were admitted to our pulmonology unit, 40 of whom were treated with HFNC due to the presence of ARDS. The intubation rate at day 30 was 52.5%, and overall mortality was 22.5%. After initiating HFNC, the SpO2/FiO2 ratio was significantly better in the group that did not require intubation (113.4±6.6 vs 93.7±6.7, p=0.020), as was the ROX index (5.0±1.6 vs 4.0±1.0, p=0.018). A ROX index less than 4.94 measured 2 to 6 h after the start of therapy was associated with increased risk of intubation (HR 4.03 [95% CI 1.18 - 13.7]; p=0.026).

CONCLUSION

High-flow therapy is a useful treatment in ARDS in order to avoid intubation or as a bridge therapy, and no increased mortality was observed secondary to the delay in intubation. After initiating HFNC, a ROX index below 4.94 predicts the need for intubation.

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.

Agarwal A, Basmaji J, Muttalib F, et al. 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. 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. Can J Anaesth. 2020;67(9):1217-1248. doi:10.1007/s12630-020-01740-2



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.

High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion.

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):2000892. Published 2020 May 14. doi:10.1183/13993003.00892-2020

Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy.

Ahn JY, An S, Sohn Y, et al. Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy. J Hosp Infect. 2020;106(3):570-576. doi:10.1016/j.jhin.2020.08.014



BACKGROUND

Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients.

AIM

To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy.

METHODS

Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR.

FINDINGS

Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT-PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room.

CONCLUSION

Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.

No evidence of increasing COVID-19 in health care workers after implementation of high flow nasal cannula: A safety evaluation.

Westafer LM, Soares WE 3rd, Salvador D, Medarametla V, Schoenfeld EM. No evidence of increasing COVID-19 in health care workers after implementation of high flow nasal cannula: A safety evaluation. Am J Emerg Med. 2021;39:158-161. doi:10.1016/j.ajem.2020.09.086



BACKGROUND

Initial recommendations discouraged high flow nasal cannula (HFNC) in COVID-19 patients, driven by concern for healthcare worker (HCW) exposure. Noting high morbidity and mortality from early invasive mechanical ventilation, we implemented a COVID-19 respiratory protocol employing HFNC in severe COVID-19 and HCW exposed to COVID-19 patients on HFNC wore N95/KN95 masks. Utilization of HFNC increased significantly but questions remained regarding HCW infection rate.

METHODS

We performed a retrospective evaluation of employee infections in our healthcare system using the Employee Health Services database and unit records of employees tested between March 15, 2020 and May 23, 2020. We assessed the incidence of infections before and after the implementation of the protocol, stratifying by clinical or non-clinical role as well as inpatient COVID-19 unit.

RESULTS

During the study period, 13.9% (228/1635) of employees tested for COVID-19 were positive. Forty-six percent of infections were in non-clinical staff. After implementation of the respiratory protocol, the proportion of positive tests in clinical staff (41.5%) was not higher than that in non-clinical staff (43.8%). Of the clinicians working in the high-risk COVID-19 unit, there was no increase in infections after protocol implementation compared with clinicians working in COVID-19 units that did not use HFNC.

CONCLUSION

We found no evidence of increased COVID-19 infections in HCW after the implementation of a respiratory protocol that increased use of HFNC in patients with COVID-19; however, these results are hypothesis generating.

Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: a case series.

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. Published 2020 May 24. doi:10.1186/s13054-020-02991-7

Prone positioning in high-flow nasal cannula for COVID-19 patients with severe hypoxemia: a pilot study.

Tu GW, Liao YX, Li QY, et al. Prone positioning in high-flow nasal cannula for COVID-19 patients with severe hypoxemia: a pilot study. Ann Transl Med. 2020;8(9):598. doi:10.21037/atm-20-3005

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.

Ferrando C, Mellado-Artigas R, Gea A, et al. Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study. Crit Care. 2020;24(1):597. Published 2020 Oct 6. doi:10.1186/s13054-020-03314-6



BACKGROUND

Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone.

METHODS

Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP.

RESULTS

A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92].

CONCLUSION

In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

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