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La terapia ad alto flusso nella polmonite da COVID-19

Articolo

Autore: Aude Garnero, Intensivist, Hôpital Sainte Musse, Tolone, Francia

Data: 04.05.2021

La terapia ad alto flusso (HFT) è una forma di supporto respiratorio non invasivo che può ridurre il tasso di intubazione e la mortalità nei pazienti con insufficienza respiratoria ipossiemica acuta (AHRF) (1). Le prime raccomandazioni in merito, a causa della preoccupazione relativa all'esposizione del personale sanitario, disincentivavano l'uso dell'HFT nei pazienti con COVID-19 (2, 3).

La terapia ad alto flusso nella polmonite da COVID-19

Contenuti chiave

  • Sebbene le raccomandazioni iniziali disincentivassero l'uso della terapia ad alto flusso nei pazienti con COVID-19, l'elevato tasso di mortalità nei pazienti ventilati meccanicamente ha determinato la graduale adozione di questo trattamento.
  • L'HFT è stata utilizzata per casi di AHRF legata a polmonite da COVID-19 con effetti positivi sull'ossigenazione e le evidenze suggeriscono che sia in grado di ridurre la necessità e la durata della ventilazione meccanica.
  • Se si utilizzano dispositivi di protezione individuale adeguati e si adottano precauzioni come la separazione dei pazienti, l'HFT può essere utilizzata sui pazienti con COVID-19 senza incorrere in un aumento misurabile delle infezioni da COVID-19 tra il personale sanitario.

A causa della morbilità e della mortalità elevate derivanti da un trattamento precoce con ventilazione meccanica invasiva (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 [correzione pubblicata 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), l'utilizzo dell'HFT è stato comunque adottato in modo graduale per i pazienti con COVID-19 grave (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. Pubblicato il 12 giugno 2020. doi:10.1186/s13054-020-03063-65). Questa revisione intende esaminare le evidenze relative agli effetti fisiologici, all'effetto sugli esiti, al rischio di contaminazione e alla combinazione di posizione prona (PP) e HFT nei pazienti con AHRF dovuta a polmonite da COVID-19.

Effetti fisiologici

Gli effetti fisiologici dell'HFT nei casi di insufficienza respiratoria ipossiemica acuta sono noti, ma non si hanno dati fisiologici specifici relativi alla polmonite da COVID-19 (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). Con l'HFT è meno probabile il trascinamento dell'aria ambientale durante l'inspirazione del paziente, pertanto l'erogazione di livelli elevati di FiO2 è più affidabile. L'HFT aumenta il volume polmonare a fine espirazione, generando così una PEEP a cui si deve il reclutamento alveolare e quindi la riduzione delle sollecitazioni polmonari locali. Questi meccanismi migliorano l'ossigenazione.

Il washout dello spazio morto fisiologico durante l'espirazione grazie al passaggio dell'aria espirata dalle vie aeree superiori aumenta l'efficienza della ventilazione. L'HFT riduce la ventilazione minuto necessaria per ottenere un livello fisiologico della CO2 arteriosa riducendo la frequenza respiratoria e lo spazio morto anatomico. La ventilazione alveolare (la ventilazione minuto meno la ventilazione dello spazio morto) resta quindi stabile, mentre la ventilazione minuto diminuisce. L'HFT riduce inoltre lo sforzo inspiratorio del paziente e abbassa il lavoro respiratorio metabolico. Infine, l'HFT migliora la meccanica respiratoria, ovvero la compliance dinamica, la pressione transpolmonare e l'omogeneità della ventilazione, oltre ad aumentare il comfort e la tolleranza del paziente rispetto alla terapia con ossigeno convenzionale.

Esiti

In uno studio osservazionale retrospettivo (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), sono stati confrontati il tasso di intubazione e la mortalità in due gruppi di pazienti, dei quali 233 (51%) sono stati trattati con ossigeno convenzionale e 146 (39%) sono stati trattati con HFT. Il tasso di intubazione risultava significativamente ridotto, dal 75% nel gruppo trattato con ossigeno convenzionale al 56% nel gruppo trattato con HFT. La mortalità al giorno 28 era del 30% nel gruppo con ossigeno convenzionale rispetto al 21% del gruppo con HFT.

Uno studio di coorte multicentrico (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. Pubblicato l'11 febbraio 2021. doi:10.1186/s13054-021-03469-w10) ha confrontato il trattamento con HFT e l'intubazione precoce in 122 pazienti (61 per ciascun gruppo). L'HFT era associata a un aumento dei giorni senza ventilatore e a una riduzione della durata del ricovero in terapia intensiva. Non è stata osservata alcuna differenza nella mortalità, tuttavia l'analisi ha evidenziato che i pazienti intubati precocemente avevano punteggi SOFA e APACHE II più elevati, ed erano quindi in condizioni peggiori già al basale.

Questi due studi suggeriscono che i pazienti con COVID-19 possano trarre vantaggio dall'HFT grazie alla riduzione di necessità e durata della ventilazione meccanica, oltre a un ricovero in terapia intensiva più breve senza impatti negativi sulla mortalità in ospedale. Non esistono tuttavia studi controllati randomizzati che confrontino gli esiti dei pazienti trattati con HFT con quelli dei pazienti trattati con ossigeno convenzionale o intubati precocemente.

Tre studi osservazionali forniscono dati relativi a pazienti con COVID-19 trattati con HFT. I tassi di intubazione erano compresi fra il 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) e il 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), e il tempo prima dell'intubazione era compreso tra 10 ore (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) e 2 giorni (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). I fattori associati a esiti positivi dell'HFT erano il trattamento con steroidi, livelli bassi di proteina C-reattiva o D-dimeri, ipertensione e abitudine al fumo (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).

Monitoraggio

I dati hanno evidenziato che i pazienti in cui l'HFT ha avuto un esito positivo avevano una frequenza respiratoria minore dopo l'inizio dell'HFT rispetto ai pazienti che successivamente hanno dovuto essere intubati (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. Pubblicato l'8 dicembre 2020. 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). In uno studio osservazionale prospettico monocentrico, il valore di taglio migliore è stato di 26 respiri al minuto dopo 30 minuti di 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).

A partire dalle variabili respiratorie utilizzate per verificare l'insufficienza respiratoria è stato calcolato l'indice ROX (frequenza respiratoria-ossigenazione), che può quindi essere utilizzato per prevedere la necessità della ventilazione invasiva. L'indice ROX corrisponde al rapporto tra SpO2/FiO2 e frequenza respiratoria. Nei casi di insufficienza respiratoria ipossiemica acuta dovuta a polmonite scorrelata da COVID-19, l'indice ROX permetteva di identificare i pazienti a basso rischio di esito negativo dell'HFT con un valore di taglio pari a 4,88 misurato dopo 12 ore di HFT (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). Nei pazienti con COVID-19, cinque studi retrospettivi (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. Pubblicato l'8 dicembre 2020. 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. Pubblicato il 24 dicembre 2020. 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. Pubblicato il 16 settembre 2020. doi:10.4081/mrm.2020.69319) hanno evidenziato che i pazienti con un esito positivo avevano un indice ROX più elevato, ma il valore di taglio per individuare i valori associati a un esito positivo risultava compreso  tra 5,55 dopo 6 ore (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. Pubblicato il 24 dicembre 2020. doi:10.1186/s12890-020-01354-w17) e 3,67 dopo 12 ore (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).

Contaminazione

La maggior parte degli studi sull'HFT nei casi di COVID-19 era sperimentale oppure eseguita su soggetti sani, pertanto non riflette i casi reali. L'Organizzazione Mondiale della Sanità ha commissionato alcune revisioni per esaminare le evidenze sull'uso dell'HFT. Sono stati analizzati sei studi di simulazione e uno studio crossover condotto su pazienti senza COVID-19; l'HFT non ha aumentato il rischio di dispersione di aerosol rispetto alla respirazione di pazienti tipici con espirazione violenta; i livelli di aerosol prodotto e le concentrazioni numeriche delle particelle rilevato con l'HFT erano simili ai valori ottenuto con nasal prongs, maschere senza rebreathing (ri-respirazione) e respirazione spontanea (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). L'HFT eseguita facendo indossare al paziente una mascherina chirurgica può quindi rappresentare una pratica ragionevole potenzialmente vantaggiosa per i pazienti ipossiemici con COVID-19 (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. Pubblicato il 14 maggio 2020. doi:10.1183/13993003.00892-202021).

Metà dei campioni ambientali su tampone prelevati dalla stanza di isolamento di un paziente con COVID-19 sottoposto a HFT e ventilazione non invasiva (NIV) sono risultati positivi. Tutti i campioni di aria sono però risultati negativi. Sono stati identificati virus vitali su un quarto delle zone esaminate. Questi risultati evidenziano l'esigenza di utilizzare dispositivi di protezione individuale (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).

In un ospedale statunitense è stata misurata l'incidenza delle infezioni da COVID-19 prima e dopo l'adozione dell'HFT/NIV. I risultati hanno evidenziato che l'utilizzo dell'HFT su un paziente con COVID-19, se associato all'uso di dispositivi di protezione individuale appropriati e separazione precauzionale dei pazienti, non ha determinato un aumento misurabile delle infezioni da COVID-19 nel personale sanitario (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 combinata con la posizione prona

La posizione prona (PP) per i pazienti svegli può migliorare l'equilibrio di ventilazione e perfusione e aprire i polmoni con atelettasia con un drenaggio adeguato dell'espettorato. Due studi descrittivi hanno riportato i dati relativi a pazienti con COVID-19 trattati con HFT e PP combinate. Nello studio condotto su 10 pazienti (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. Pubblicato il 24 maggio 2020. doi:10.1186/s13054-020-02991-724) la PaO2/FiO2 era più elevata dopo il posizionamento in PP. La PaCO2 era aumentata, restando comunque al di sotto dei valori fisiologici (solitamente si osserva ipocapnia nei pazienti con COVID-19 che respirano spontaneamente). Nessuno dei pazienti ha dovuto essere intubato. Nell'altro studio, condotto su nove pazienti (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), è stata utilizzata la PP due volte al giorno con una mediana di 5 (3-8) procedure per soggetto. La durata mediana della procedura è stata di 2 (1-4) ore. Dopo il posizionamento in PP, i valori di SaO2 e PaO2 sono aumentati. Nello studio il valore di PaCO2 è diminuito, ma i pazienti erano in condizione di ipocapnia già dall'inizio. È stato necessario intubare due pazienti.

In uno studio di coorte adattivo prospettico e multicentrico (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. Pubblicato il 6 ottobre 2020. doi:10.1186/s13054-020-03314-626), 199 pazienti sono stati trattati con l'HFT e 55 di questi (28%) sono stati collocati in posizione prona. L'utilizzo della PP come terapia integrativa dell'HFT non ha ridotto il rischio di intubazione: 82 (41%) pazienti hanno dovuto essere intubati: 60 (41%) nel gruppo trattato con HFNO e 22 (40%) nel gruppo trattato con HFT + PP. Il tempo trascorso dall'HFT all'intubazione era maggiore nel gruppo trattato con HFT + PP. La mortalità non è stata influenzata dall'utilizzo della PP. Nel gruppo trattato con HFT + PP era presente una forte tendenza verso un ritardo di 2 giorni nell'intubazione; la mortalità era simile in entrambi i gruppi. In questo studio, la PP è stata però indicata in base a criteri medici anziché essere utilizzata uniformemente. Gli autori non sono stati in grado di determinare se i medici utilizzassero la PP come pratica standard per il trattamento dei pazienti con COVID-19 oppure se la adottassero come strategia di soccorso. Si è tenuto conto della PP per l'analisi solo nei casi in cui la durata era > 16 h/giorno e i risultati non possono essere ritenuti validi per i pazienti collocati in posizione prona per periodi di tempo più brevi, ma questo fattore non suggeriva una prognosi peggiore nel caso di intubazione ritardata.

Conclusione

L'HFT è stata utilizzata per l'AHRF correlata a polmonite da COVID-19 con effetti positivi sull'ossigenazione. I pazienti in cui l'HFT ha avuto esito negativo hanno registrato un tasso di mortalità maggiore, poiché erano in condizioni peggiori già al basale. È possibile utilizzare l'indice ROX come predittore dell'intubazione, ma la discussione è ancora aperta per quanto riguarda il valore di taglio. È emerso che, se utilizzata con precauzioni e dispositivi di protezione individuale adeguati, l'HFT non aumenta le contaminazioni o le infezioni nel personale sanitario. Occorre approfondire le ricerche sull'HFT combinata con la PP.

Tutti i ventilatori di Hamilton Medical erogano la terapia con ossigeno ad alto flusso come funzionalità di serie oppure opzionale. Non occorre utilizzare dispositivi aggiuntivi ed è possibile alternare la terapia alla ventilazione non invasiva in base alle esigenze, modificando semplicemente l'interfaccia per passare da una modalità all'altra. Ora anche l'umidificatore HAMILTON-H900 è dotato di una speciale modalità per la terapia con ossigeno ad alto flusso, con impostazioni dedicate che consentono al dispositivo di supportare la terapia con ossigeno ad alto flusso in tutti i gruppi di pazienti.

 

Citazioni complete a fondo pagina: (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 [pubblicato online prima della stampa, 27 febbraio 2020]. 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. Pubblicato il 13 aprile 2020. doi:10.1002/emp2.120633)

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Bibliografia

  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
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  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
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  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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How to use high flow therapy in COVID-19 acute hypoxemic respiratory failure

High flow therapy (HFT) has been used widely during the COVID-19 pandemic. Published clinical experience is based mainly on retrospective studies and describes the main settings and the failure rate.