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High flow therapy in COVID-19 pneumonia

Article

Author: Aude Garnero, Intensivist, Hôpital Sainte Musse, Toulon, France

Date of first publication: 04.05.2021

High-flow therapy (HFT) is a non-invasive form of respiratory support that can lower the intubation rate and mortality in patients with acute hypoxemic respiratory failure (AHRF) (1). Driven by concerns about the exposure of healthcare workers, initial recommendations discouraged the use of HFT in COVID-19 patients (2, 3).

High flow therapy in COVID-19 pneumonia

Takeaway messages

  • Although initial recommendations discouraged the use of high flow therapy in COVID-19 patients, high mortality rates in mechanically ventilated patients resulted in its gradual implementation.
  • HFT has been used in COVID-19 pneumonia related AHRF with favorable effects on oxygenation and evidence suggests it may decrease the need for mechanical ventilation and its duration.
  • If appropriate personal protective equipment is used and cohorting precautions are taken, HFT may be applied in COVID-19 patients without leading to a measurable increase in COVID-19 infections in healthcare workers.

However, due to the high morbidity and mortality resulting from early invasive mechanical ventilation (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​), the use of HFT was gradually implemented in patients with severe COVID-19 (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​). This review looks at the evidence regarding the physiologic effects, the effect on outcomes, the risk of contamination, and the combination of prone positioning (PP) and HFT in patients with AHRF due to COVID-19 pneumonia.

Physiologic effects

The physiologic effects of HFT in acute hypoxemic respiratory failure are well-established, but there is no physiologic data specifically for COVID-19 pneumonia (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​). HFT is less likely to allow the entrainment of room air during patient inspiration, ensuring more reliable delivery of high FiO2 levels. HFT increases the end-expiratory lung volume, thereby generating PEEP that is responsible for alveolar recruitment and hence reducing regional lung strain. These mechanisms improve oxygenation.

The washout of physiologic dead space by flushing expired air from the upper airway during expiration improves ventilatory efficiency. HFT reduces the minute ventilation needed to obtain a physiologic arterial CO2 level by decreasing the respiratory rate and anatomical dead space. Therefore, the alveolar ventilation (minute ventilation minus dead-space ventilation) remains stable, whereas the minute ventilation decreases. HFT also reduces the patient’s inspiratory effort and lessens the metabolic work of breathing. Finally, HFT improves respiratory mechanics, i.e., dynamic compliance, transpulmonary pressure, and ventilation homogeneity, and enhances patient comfort and tolerance when compared with conventional oxygen.

Outcomes

In a retrospective observational study (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​), intubation rate and mortality were compared between 233 (51%) patients receiving standard oxygen and 146 (39%) patients treated with HFT. The intubation rate was significantly reduced from 75% in the standard oxygen group to 56% in the HFT group. Mortality at day 28 was 30% in the standard oxygen group versus 21% in the HFT group.

A multicenter cohort study (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​) compared treatment with HFT and early intubation in 122 patients (61 patients in each group). HFT was associated with an increase in ventilator-free days and a reduction in the ICU length of stay. No difference was observed in mortality; however, analysis showed that patients receiving early intubation had higher SOFA and APACHE II scores and were thus sicker at baseline.

These two studies suggest that COVID-19 patients may benefit from HFT by decreasing the need for mechanical ventilation and its duration, as well as decreasing the ICU length of stay without having a negative impact on hospital mortality. However, there are no randomized controlled trials comparing outcomes in HFT patients with conventional oxygen or early intubation.

Three observational studies provide data from COVID-19 patients treated with HFT. Intubation rates were between 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​) and 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​), and the time to intubation between 10 h (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​) and 2 days (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​). Factors associated with successful outcomes with HFT were steroid treatment, low C-reactive protein or D-dimer levels, hypertension, and smoking (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

Data has shown that patients in whom HFT succeeded had a lower respiratory rate after HFT initiation than those patients who subsequently needed intubation (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​). In a monocentric prospective observational study, the best cut-off value was 26 breaths per minute after 30 minutes of 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​).

The ROX (Respiratory rate-OXygenation) index is calculated from the respiratory variables that assess respiratory failure and can thus be used to predict the need for invasive ventilation. It represents the ratio of SpO2/FIO2 to RR. In acute hypoxemic respiratory failure due to non-COVID-19 pneumonia, the ROX index identified patients at low risk of HFT failure with a cut-off value of 4.88 measured after 12 hours of 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​). In COVID-19 patients, five retrospective studies (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​) showed that patients with a successful outcome had a higher ROX index, but the cut-off point for values associated with success varied  between 5.55 after 6 hours (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​) 3.67 after 12 hours (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​).

Contamination

The majority of studies on HFT in COVID-19 are either experimental or carried out on healthy subjects and therefore do not reflect real life. The World Health Organization commissioned reviews to examine the evidence on the use of HFT: Six simulation studies and one crossover study on non-COVID-19 patients were analyzed; HFT did not increase the risk of aerosol dispersion in comparison to typical patient breathing with violent exhalation; aerosol production levels and particle number concentrations found with HFT were similar to those with nasal prongs, non-rebreather masks, and spontaneous breathing (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​). HFT with a surgical mask on the patient’s face could thus be a reasonable practice that may benefit hypoxemic COVID-19 patients (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​).

Half of the environmental swab samples taken from the isolation room of a COVID-19 patient receiving HFT and non-invasive ventilation (NIV) showed positive results. However, all air samples were negative. Viable viruses were identified on one quarter of the sites. These findings highlight the need for use of personal protective equipment (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​).

The incidence of COVID-19 infections before and after the implementation of HFT/NIV was measured in a US hospital. Results showed that use of HFT in a COVID-19 patient, when associated with the use of appropriate personal protective equipment and cohorting precautions, did not lead to a measurable increase in COVID-19 infections in healthcare workers (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 combined with prone positioning

Awake PP may improve the mismatch of ventilation-perfusion and open the atelectatic lungs by means of adequate sputum drainage. Two descriptive studies reported data from COVID-19 patients treated with HFT combined with PP. In the study of 10 patients (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​), PaO2/FiO2 was higher after PP. PaCO2 increased, but remained under the physiologic values (hypocapnia is usually observed in spontaneously breathing COVID-19 patients). None of the patients required intubation. In the other study of nine patients (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​), PP was applied twice daily with a median of 5 (3-8) procedures per subject. The median duration was 2 (1-4) hours. SaO2 and PaO2 increased after PP. PaCO2 decreased in the study, but patients were hypercapnic at the beginning. Two patients required intubation.

In a prospective 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/s13054-020-03314-626​), 199 patients received HFT and 55 of these (28%) were pronated. The use of PP as an adjunctive therapy to HFT did not reduce the risk of being intubated: 82 (41%) patients required intubation, 60 (41%) in the HFNO group and 22 (40%) in HFT + PP group. The time from HFT to intubation was longer in the HFT + PP. Mortality was not affected by the use of PP. In the HFT + PP group, there was a strong trend towards a delay in intubation of 2 days; mortality was similar in both groups. In this study however, PP was indicated by medical criteria and not applied uniformly. The authors were unable to determine whether clinicians had used PP as standard practice for COVID-19 patients or as a rescue strategy. PP was only considered for analysis if the duration was > 16 h/day and results could not be extended to patients pronated for shorter periods of time, but this did not suggest a worse prognosis in the case of delayed intubation.

Conclusion

HFT has been used in COVID-19 pneumonia related AHRF with favorable effects on oxygenation. Those patients who failed with HFT had a higher mortality rate because they were sicker at baseline. The ROX index may be used as a predictor of intubation, but the optimal cut-off is open to debate. If used with the appropriate protective equipment and precautions, HFT was shown not to increase contamination or infection of healthcare workers. The combination of HFT and PP requires further investigation.

High flow oxygen therapy on Hamilton Medical ventilators

Ventilators from Hamilton Medical offer high flow oxygen therapy as a standard or optional feature (Some features are options. Not all features/products are available in all markets. Specifications are subject to change without notice.A​​) and compatible high flow interfaces. No additional device or ventilator is required and the therapy can be alternated with noninvasive ventilation as needed by changing the interface and simply switching modes.

The HAMILTON-H900 humidifier now also offers a special high flow oxygen therapy mode with dedicated settings to support high flow oxygen therapy for all patient groups.

Full citations below: (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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Footnotes

  • A. Some features are options. Not all features/products are available in all markets. Specifications are subject to change without notice.

References

  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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