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Can we predict the failure of HFNC in patients with acute hypoxemic respiratory failure?

Article

Author: Caroline Brown

Date of first publication: 16.10.2020

Last change: 06.10.2020

First published: 16.07.2020 ROX (values) at 12 hours after HFNC initiation (previously: intubation) were predictors of HFNC failure.

The coronavirus pandemic has stretched many hospitals’ resources to the limit. Patients are requiring respiratory support on an unprecedented scale and a possible – or in some cases very real – shortage of ventilators is forcing institutions to weigh up the risks and benefits of alternative forms of therapy.

Can we predict the failure of HFNC in patients with acute hypoxemic respiratory failure?

Takeaway messages

  • Delivery of oxygen by high flow nasal cannula has a range of benefits including greater patient comfort, and improved oxygenation and ventilation.
  • One of the major challenges is identifying those patients in which HFNC is likely to fail, as delayed intubation may result in worse outcomes.
  • An index defined as the ratio of SpO2/FiO2 to the respiratory rate is an easy-to-use bedside tool that can help identify the need for mechanical ventilation in pneumonia patients with AHRF treated with HFNC.

Risks versus benefits for clinicians and patients

On the one hand, evidence on the use of oxygen delivered by high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure (AHRF) has demonstrated its superiority to standard oxygen therapy by facemask in many respects, including better tolerance, and improved oxygenation and work of breathing (Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413. 1​, Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients. J Crit Care. 2010;25(3):463-468. doi:10.1016/j.jcrc.2009.06.0502​, Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. doi:10.1164/rccm.201402-0364OC3​). It has also been shown to reduce the need for intubation compared to conventional oxygen (Rochwerg B, Granton D, Wang DX, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019;45(5):563-572. doi:10.1007/s00134-019-05590-54,​ 5, Ou X, Hua Y, Liu J, Gong C, Zhao W. Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials. CMAJ. 2017;189(7):E260-E267. doi:10.1503/cmaj.1605706​). A network analysis of 25 randomized controlled trials investigating different noninvasive oxygenation strategies in adult AHRF patients showed that high-flow nasal oxygen was associated with a lower risk of intubation compared with standard oxygen therapy (Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. 2020;324(1):57-67. doi:10.1001/jama.2020.95247​). However, in the light of conflicting evidence with respect to both reduced intubation rates and mortality, there are currently no specific recommendations for using high flow nasal cannula devices in COVID-19 patients. This uncertainty is compounded by concerns that use of high flow devices may increase virus dispersion. In this respect too there are many unanswered questions, such as to what extent aerolization translates into a significant infection risk, how that risk compares with risks posed by other forms of treatment and to what extent healthcare workers can protect themselves. Although the available evidence on generation and dispersion of bio-aerosols indicates that HFNC poses no greater risk than standard oxygen masks (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:10.1183/13993003.00892-20208​), many clinicians are reluctant to apply this treatment in a COVID-19 setting. Furthermore, guidelines issued by organizations around the world for the treatment of COVID-19 patients with respect to HFNC vary greatly. However, considering the high efficacy of HFNC with respect to oxygenation, the fact that for some patients it may be almost the only viable alternative, and the significance of lower intubation rates in light of limited resources, some are urging for an open-minded approach and a careful look at the risk-benefit profile for both clinicians and patients (Lyons C, Callaghan M. The use of high-flow nasal oxygen in COVID-19. Anaesthesia. 2020;75(7):843-847. doi:10.1111/anae.150738​, Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59(4):485-490. doi:10.4187/respcare.023979​).

Application and benefits in a general setting

There are several mechanisms of action for HFNC that translate into a range of benefits, including greater patient comfort (Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413. 1​, Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients. J Crit Care. 2010;25(3):463-468. doi:10.1016/j.jcrc.2009.06.0502​, Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. doi:10.1164/rccm.201402-0364OC10​), improved airway secretion clearance and less work of breathing (Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis. 2008;5(2):81-86. doi:10.1177/147997230708719011​, Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24(11):1920-1929. doi:10.1097/00003246-199611000-0002512​), improved ventilation and oxygen delivery (Sztrymf B, Messika J, Mayot T, Lenglet H, Dreyfuss D, Ricard JD. Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study. J Crit Care. 2012;27(3):324.e9-324.e3.24E13. doi:10.1016/j.jcrc.2011.07.07513​, Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780-1786. doi:10.1007/s00134-011-2354-614​, Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard JD. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. doi:10.4187/respcare.0157515​). The high flow rate ensures a stable fraction of inspired oxygen (FiO2) without room air entrainment (Sim MA, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated. Anaesthesia. 2008;63(9):938-940. doi:10.1111/j.1365-2044.2008.05536.x16​, Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011;39(6):1103-1110. doi:10.1177/0310057X110390062017​, Wagstaff TA, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia. 2007;62(5):492-503. doi:10.1111/j.1365-2044.2007.05026.x18​). In comparison with delivery by face mask, HFNC has been shown to result in a higher partial pressure of arterial oxygen (PaO2), lower respiratory rate (RR), more comfort, less mouth dryness, and less dyspnea (1). Lastly, HFNC generates a positive end-expiratory pressure (PEEP) effect (Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20(4):126-131. doi:10.1016/j.aucc.2007.08.00119​) and increases in end-expiratory lung volume (EELV) (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.201605-0916OC20​, Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107(6):998-1004. doi:10.1093/bja/aer26521​) and tidal volume (Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107(6):998-1004. doi:10.1093/bja/aer26521​). However, as many of the proven benefits are physiologic, there are not yet absolute indications for the use of HFNC. One of the major challenges is identifying those patients in which HFNC is likely to fail, to ensure intubation is not delayed unnecessarily. In such patients, delayed intubation is associated with worse outcomes (Kang BJ, Koh Y, Lim CM, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015;41(4):623-632. doi:10.1007/s00134-015-3693-522​); therefore, identification of variables that may help clinicians to make a timely decision to intubate would impact positively on clinical practice. A study by Roca et al. (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.2016.05.02223​) looked at the use of an index as an easy-to-use bedside tool for accurately identifying the need for mechanical ventilation in pneumonia patients with AHRF treated with HFNC.

The ROX index

The ROX index is defined as the ratio of SpO2 (oxygen saturation as measured by pulse oximetry)/FiO2 (fraction of inspired oxygen) to the respiratory rate. SpO2/FiO2 has been shown to have a positive association with the success of HNFC, while RR has an inverse association. In their results published in 2016, Roca et al. concluded that the ROX index, which combined both parameters, could successfully be used to identify patients who were at low risk of HFNC failure and could therefore continue to receive HFNC after 12 hours (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.2016.05.02223​). Subsequent results published in 2019 (Roca O, Caralt B, Messika J, et al. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019;199(11):1368-1376. doi:10.1164/rccm.201803-0589OC24​) showed that while SpO2/FiO2 was almost as good as the ROX index, adding RR further improved the diagnostic accuracy. In this 2-year multicenter prospective observational cohort study including 191 patients with pneumonia-related ARF treated with HFNC, the prediction accuracy of the index was also shown to increase over time, from 2 h to 6 h and then 12 h. ROX index values measured at 12 hours after the start of HFNC demonstrated the best prediction accuracy. At all time points, patients with ROX ≥ 4.88 were less likely to be intubated. ROX < 2.85 at 2 hours, < 3.47 at 6 hours, and < 3.85 at 12 hours after intubation, respectively, were predictors of HFNC failure. The patients in whom therapy failed were those who showed a smaller increase in ROX index values during the 12-hour period. The authors concluded that the ROX index may help physicians predict which patients might need intubation and consequently avoid delaying mechanical ventilation. 

Correlation between ROX index and increase in flow

Based on previous data from patients with AHRF treated with HFNC, which showed that the set flow rate has a significant effect on oxygenation and RR (Mauri T, Alban L, Turrini C, et al. Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med. 2017;43(10):1453-1463. doi:10.1007/s00134-017-4890-125​), Mauri et al. (Mauri T, Carlesso E, Spinelli E, et al. Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. J Crit Care. 2019;53:183-185. doi:10.1016/j.jcrc.2019.06.02026​) subsequently investigated whether an increase in the set flow rate might impact the ROX index values. In addition, they looked at a possible association between a more severe condition at baseline and an improvement in ROX index values at the higher rate. Fifty-seven hypoxemic patients underwent two, 20-minute sessions of HFNC, one with the gas flow at 30 l/min and one at 60 l/min. The ROX index was measured at each flow rate. Results showed that the increase in flow rate from 30 to 60 l/min during a “flow challenge” session correlated with a small but significant increase in the ROX index, with forty patients demonstrating an increase in ROX index at the higher flow rate. These patients were also shown to be in a more severe condition, with lower SPO2/FiO2, higher RR and lower ROX index at 30 l/min, and as such, responded more positively to the flow increase. In addition, the improvement in the ROX index was shown to correlate with the increase in EELV at the higher flow rate. Therefore, this study showed that the set flow rate may affect the ROX index value. Such a change in the ROX index after a 20-minute “flow challenge” could be a simple and quick means of identifying severe patients in need of closer monitoring. Furthermore, standardizing measurement of the ROX index at the lowest flow rate of 30 l/min may help better predict the success or failure of HFNC.

What is next?

On top of the limitations of previous studies, concerns have been expressed about the  relationship between the SpO2/FiO2 ratio and the PaO2 (partial pressure of arterial oxygen)/FiO2 ratio that may not always be so linear (Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.00327​). However, a study by Chen et al. in 2015 showed that characteristics and outcomes in ARDS diagnosed by the SpO2/FIO2 ratio were very similar to those in patients diagnosed by the PaO2/FiO2 ratio (Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.00328​). To date, all evidence documented with respect to the ROX index has been based on observational studies. A randomized controlled trial is currently underway to assess whether use of the ROX index in addition to traditional criteria for determining the need for intubation in AHRF patients is both feasible and associated with earlier intubation.

Conclusion

The ROX index is an accurate, simple-to-use tool for any staff member at the bedside. As such, it could potentially be measured routinely in those patients undergoing HFNC. Further research will shed light on the feasibility and usefulness of using the ROX index in combination with traditional criteria for determining whether intubation is necessary. 

Ventilators from Hamilton Medical offer high flow oxygen therapy as a standard or optional feature, in addition to continuous SpO2 and SpO2/FiO2 measurement (Some features are options. Not all features/products are available in all markets. Specifications are subject to change without notice.A​​). We also offer 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. 

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. Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413.
  2. 2. Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients. J Crit Care. 2010;25(3):463-468. doi:10.1016/j.jcrc.2009.06.050
  3. 6. Ou X, Hua Y, Liu J, Gong C, Zhao W. Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials. CMAJ. 2017;189(7):E260-E267. doi:10.1503/cmaj.160570
  4. 7. Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. 2020;324(1):57-67. doi:10.1001/jama.2020.9524
  5. 8. 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
  6. 8. Lyons C, Callaghan M. The use of high-flow nasal oxygen in COVID-19. Anaesthesia. 2020;75(7):843-847. doi:10.1111/anae.15073
  7. 9. Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59(4):485-490. doi:10.4187/respcare.02397
  8. 10. Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. doi:10.1164/rccm.201402-0364OC
  9. 11. Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis. 2008;5(2):81-86. doi:10.1177/1479972307087190
  10. 12. Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24(11):1920-1929. doi:10.1097/00003246-199611000-00025
  11. 13. Sztrymf B, Messika J, Mayot T, Lenglet H, Dreyfuss D, Ricard JD. Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study. J Crit Care. 2012;27(3):324.e9-324.e3.24E13. doi:10.1016/j.jcrc.2011.07.075
  12. 14. Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780-1786. doi:10.1007/s00134-011-2354-6
  13. 15. Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard JD. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. doi:10.4187/respcare.01575
  14. 16. Sim MA, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated. Anaesthesia. 2008;63(9):938-940. doi:10.1111/j.1365-2044.2008.05536.x
  15. 17. Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011;39(6):1103-1110. doi:10.1177/0310057X1103900620
  16. 18. Wagstaff TA, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia. 2007;62(5):492-503. doi:10.1111/j.1365-2044.2007.05026.x
  17. 19. Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20(4):126-131. doi:10.1016/j.aucc.2007.08.001
  18. 20. 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
  19. 21. Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107(6):998-1004. doi:10.1093/bja/aer265
  20. 22. Kang BJ, Koh Y, Lim CM, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015;41(4):623-632. doi:10.1007/s00134-015-3693-5
  21. 23. 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
  22. 24. Roca O, Caralt B, Messika J, et al. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019;199(11):1368-1376. doi:10.1164/rccm.201803-0589OC
  23. 25. Mauri T, Alban L, Turrini C, et al. Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med. 2017;43(10):1453-1463. doi:10.1007/s00134-017-4890-1
  24. 26. Mauri T, Carlesso E, Spinelli E, et al. Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. J Crit Care. 2019;53:183-185. doi:10.1016/j.jcrc.2019.06.020
  25. 27. Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.003
  26. 28. Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.003
  27. 4,. Rochwerg B, Granton D, Wang DX, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019;45(5):563-572. doi:10.1007/s00134-019-05590-5

High-flow oxygen therapy in acute respiratory failure.

Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413.



OBJECTIVE

To compare the comfort of oxygen therapy via high-flow nasal cannula (HFNC) versus via conventional face mask in patients with acute respiratory failure. Acute respiratory failure was defined as blood oxygen saturation < 96% while receiving a fraction of inspired oxygen > or = 0.50 via face mask.

METHODS

Oxygen was first humidified with a bubble humidifier and delivered via face mask for 30 min, and then via HFNC with heated humidifier for another 30 min. At the end of each 30-min period we asked the patient to evaluate dyspnea, mouth dryness, and overall comfort, on a visual analog scale of 0 (lowest) to 10 (highest). The results are expressed as median and interquartile range values.

RESULTS

We included 20 patients, with a median age of 57 (40-70) years. The total gas flow administered was higher with the HFNC than with the face mask (30 [21.3-38.7] L/min vs 15 [12-20] L/min, P < .001). The HFNC was associated with less dyspnea (3.8 [1.3-5.8] vs 6.8 [4.1-7.9], P = .001) and mouth dryness (5 [2.3-7] vs 9.5 [8-10], P < .001), and was more comfortable (9 [8-10]) versus 5 [2.3-6.8], P < .001). HFNC was associated with higher P(aO(2)) (127 [83-191] mm Hg vs 77 [64-88] mm Hg, P = .002) and lower respiratory rate (21 [18-27] breaths/min vs 28 [25-32] breaths/min, P < .001), but no difference in P(aCO(2)).

CONCLUSIONS

HFNC was better tolerated and more comfortable than face mask. HFNC was associated with better oxygenation and lower respiratory rate. HFNC could have an important role in the treatment of patients with acute respiratory failure.

High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients.

Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: a randomized crossover trial in extubated patients. J Crit Care. 2010;25(3):463-468. doi:10.1016/j.jcrc.2009.06.050



PURPOSE

Oxygen delivery after extubation is critical to maintain adequate oxygenation and to avoid reintubation. The delivery of oxygen in such situations is usually by high-flow face mask (HFFM). Yet, this may be uncomfortable for some patients. A recent advance in oxygen delivery technology is high-flow nasal prongs (HFNP). There are no randomized trials comparing these 2 modes.

METHODS

Patients were randomized to either protocol A (n = 25; HFFM followed by HFNP) or protocol B (n = 25; HFNP followed by HFFM) after a stabilization period of 30 minutes after extubation. The primary objective was to compare the efficacy of HFNP to HFFM in maintaining gas exchange as measured by arterial blood gas. Secondary objective was to compare the relative effects on heart rate, blood pressure, respiratory rate, comfort, and tolerance.

RESULTS

Patients in both protocols were comparable in terms of age, demographic, and physiologic variables including arterial blood gas, blood pressure, heart rate, respiratory rate, Glasgow Coma Score, sedation, and Acute Physiology and Chronic Health Evaluation (APACHE) III scores. There was no significant difference in gas exchange, respiratory rate, or hemodynamics. There was a significant difference (P = .01) in tolerance, with nasal prongs being well tolerated. There was a trend (P = .09) toward better patient comfort with HFNP.

CONCLUSIONS

High-flow nasal prongs are as effective as HFFM in delivering oxygen to extubated patients who require high-flow oxygen. The tolerance of HFNP was significantly better than in HFFM.

Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials.

Ou X, Hua Y, Liu J, Gong C, Zhao W. Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials. CMAJ. 2017;189(7):E260-E267. doi:10.1503/cmaj.160570



BACKGROUND

Conflicting recommendations exist on whether high-flow nasal cannula (HFNC) oxygen therapy should be administered to adult patients in critical care with acute hypoxemic respiratory failure. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate its effect on intubation rates.

METHODS

We searched electronic databases from inception to April 2016. We included RCTs that compared HFNC oxygen therapy with usual care (conventional oxygen therapy or noninvasive ventilation) in adults with acute hypoxemic respiratory failure. Because of the different methodologies and variation in clinical outcomes, we conducted 2 subgroup analyses according to oxygen therapy used and disease severity. We pooled data using random-effects models. The primary outcome was the proportion of patients who required endotracheal intubation.

RESULTS

We included 6 RCTs (n = 1892). Compared with conventional oxygen therapy, HFNC oxygen therapy was associated with a lower intubation rate (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.38 to 0.94; I2 = 49%). We found no significant difference in the rate between HFNC oxygen therapy and noninvasive ventilation (RR 0.86, 95% CI 0.68 to 1.09; I2 = 2%). In the subgroup analysis by disease severity, no significant differences were found in the intubation rate between HFNC oxygen therapy and either conventional oxygen therapy or noninvasive ventilation (interaction p = 0.3 and 0.4, respectively).

INTERPRETATION

The intubation rate with HFNC oxygen therapy was lower than the rate with conventional oxygen therapy and similar to the rate with noninvasive ventilation among patients with acute hypoxemic respiratory failure. Larger, high-quality RCTs are needed to confirm these findings.

Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis.

Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA. 2020;324(1):57-67. doi:10.1001/jama.2020.9524



Importance

Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure.

Objective

To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure.

Data Sources

The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race.

Study Selection

Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy.

Data Extraction and Synthesis

Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings.

Main Outcomes and Measures

The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days.

Results

Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, -0.19 [95% CrI, -0.37 to -0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, -0.06 [95% CrI, -0.15 to -0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, -0.32 [95% CrI, -0.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high.

Conclusions and Relevance

In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.

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

The use of high-flow nasal oxygen in COVID-19.

Lyons C, Callaghan M. The use of high-flow nasal oxygen in COVID-19. Anaesthesia. 2020;75(7):843-847. doi:10.1111/anae.15073

High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study.

Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59(4):485-490. doi:10.4187/respcare.02397



OBJECTIVE

Compare the short-term benefit of high-flow nasal cannula (HFNC) with non-rebreathing mask in terms of change in dyspnea, physiologic variables, and patient comfort in subjects after endotracheal extubation.

METHODS

A randomized crossover study was conducted in a 10-bed respiratory care unit in a university hospital. Seventeen mechanically ventilated subjects were randomized after extubation to either Protocol A (applied HFNC for 30 min, followed by non-rebreathing mask for another 30 min) or Protocol B (applied non-rebreathing mask for 30 min, followed by HFNC for another 30 min). The level of dyspnea, breathing frequency, heart rate, blood pressure, oxygen saturation, and patient comfort were recorded. The results were expressed as mean ± SD, frequency, or percentage. Categorical variables were compared by chi-square test or Fisher exact test, and continuous variables were compared by dependent or paired t test. Statistical significance was defined as P < .05.

RESULTS

Seventeen subjects were divided into 2 groups: 9 subjects in Protocol A and 8 subjects in Protocol B. The baseline characteristics and physiologic parameters before extubation were not significantly different in each protocol. At the end of study, HFNC indicated less dyspnea (P = .04) and lower breathing frequency (P = .009) and heart rate (P = .006) compared with non-rebreathing mask. Most of the subjects (88.2%) preferred HFNC to non-rebreathing mask.

CONCLUSIONS

HFNC can improve dyspnea and physiologic parameters, including breathing frequency and heart rate, in extubated subjects compared with conventional oxygen therapy. This device may have a potential role for use after endotracheal extubation.

Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome.

Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. doi:10.1164/rccm.201402-0364OC



RATIONALE

Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce.

OBJECTIVES

To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes.

METHODS

Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation.

MEASUREMENTS AND MAIN RESULTS

PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P < 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P < 0.001) in the NHF group.

CONCLUSIONS

Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).

Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis. 2008;5(2):81-86. doi:10.1177/1479972307087190

Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p < 0.07). Warm air humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa.

Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24(11):1920-1929. doi:10.1097/00003246-199611000-00025



OBJECTIVE

To review the available literature on the relationship between the humidity and temperature of inspired gas and airway mucosal function.

DATA SOURCES

International computerized databases and published indices, experts in the field, conference proceedings, bibliographies.

STUDY SELECTION/DATA EXTRACTION

Two hundred articles/texts on respiratory tract physiology and humidification were reviewed. Seventeen articles were selected from 40 articles for inclusion in the published data verification of the model. Selection was by independent reviewers. Extraction was by consensus, and was based on finding sufficient data.

DATA SYNTHESIS

A relationship exists between inspired gas humidity and temperature, exposure time to a given humidity level, and mucosal function. This relationship can be modeled and represented as an inspired humidity magnitude vs. exposure time map. The model is predictive of mucosal function and can be partially verified by the available literature. It predicts that if inspired humidity deviates from an optimal level, a progressive mucosal dysfunction begins. The greater the humidity deviation, the faster the mucosal dysfunction progresses.

CONCLUSIONS

A model for the relationship between airway mucosal dysfunction and the combination of the humidity of inspired gas and the duration over which the airway mucosa is exposed to that humidity is proposed. This model suggests that there is an optimal temperature and humidity above which, and below which, there is impaired mucosal function. This optimal level of temperature and humidity is core temperature and 100% relative humidity. However, existing data are only sufficient to test this model for gas conditions below core temperature and 100% relative humidity. These data concur with the model in that region. No studies have yet looked at this relationship beyond 24 hrs. Longer exposure times to any given level of inspired humidity and inspired gas temperatures and humidities above core temperature and 100% relative humidity need to be studied to fully verify the proposed model.

Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study.

Sztrymf B, Messika J, Mayot T, Lenglet H, Dreyfuss D, Ricard JD. Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study. J Crit Care. 2012;27(3):324.e9-324.e3.24E13. doi:10.1016/j.jcrc.2011.07.075



PURPOSE

The purpose of this study was to determine the impact of high-flow nasal cannula oxygen (HFNC) on patients with acute respiratory failure (ARF) in comparison with conventional oxygen therapy.

MATERIALS AND METHODS

This was a prospective observational study. Patients with persistent ARF despite oxygen with conventional facemask without indication for immediate intubation were treated with HFNC oxygen. Clinical respiratory parameters and arterial blood gases were compared under conventional and HFNC oxygen therapy.

RESULTS

Twenty patients, aged 59 years (38-75 years) and SAPS2 (simplified acute physiology score) 33 (26.5-38), were included in the study. Etiology of ARF was mainly pneumonia (n = 11), sepsis (n = 3), and miscellaneous (n = 6). Use of HFNC enabled a significant reduction of respiratory rate, 28 (26-33) vs 24.5 (23-28.5) breath per minute (P = .006), and a significant increase in oxygen saturation, oxygen saturation as measured by pulse oximetry 93.5% (90-98.5) vs 98.5% (95.5-100) (P = .0003). Use of HFNC significantly increased Pao(2) from 8.73 (7.13-11.13) to 15.27 (9.66-25.6) kPa (P = .001) and moderately increased Paco(2), 5.26 (4.33-5.66) to 5.73 (4.8-6.2) kPa (P = .005) without affecting pH. Median duration of HFNC was 26.5 (17-121) hours. Six patients were secondarily intubated, and 3 died in the intensive care unit.

CONCLUSION

Use of HFNC in patients with persistent ARF was associated with significant and sustained improvement of both clinical and biologic parameters.

Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study.

Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780-1786. doi:10.1007/s00134-011-2354-6



PURPOSE

To evaluate the efficiency, safety and outcome of high flow nasal cannula oxygen (HFNC) in ICU patients with acute respiratory failure.

METHODS

Pilot prospective monocentric study. Thirty-eight patients were included. Baseline demographic and clinical data, as well as respiratory variables at baseline and various times after HFNC initiation during 48 h, were recorded. Arterial blood gases were measured before and after the use of HFNC. Noise and discomfort were monitored along with outcome and need for invasive mechanical ventilation.

RESULTS

HFNC significantly reduced the respiratory rate, heart rate, dyspnea score, supraclavicular retraction and thoracoabdominal asynchrony, and increased pulse oxymetry. These improvements were observed as early as 15 min after the beginning of HFNC for respiratory rate and pulse oxymetry. PaO(2) and PaO(2)/FiO(2) increased significantly after 1 h HFNC in comparison with baseline (141 ± 106 vs. 95 ± 40 mmHg, p = 0.009 and 169 ± 108 vs. 102 ± 23, p = 0.036; respectively). These improvements lasted throughout the study period. HFNC was used for a mean duration of 2.8 days and a maximum of 7 days. It was never interrupted for intolerance. No nosocomial pneumonia occurred during HFNC. Nine patients required secondary invasive mechanical ventilation. Absence of a significant decrease in the respiratory rate, lower oxygenation and persistence of thoracoabdominal asynchrony after HFNC initiation were early indicators of HFNC failure.

CONCLUSIONS

HFNC has a beneficial effect on clinical signs and oxygenation in ICU patients with acute respiratory failure. These favorable results constitute a prerequisite to launching a randomized controlled study to investigate whether HFNC reduces intubation in these patients.

Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy.

Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard JD. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. doi:10.4187/respcare.01575



OBJECTIVE

Heated and humidified high flow nasal cannula oxygen therapy (HFNC) represents a new alternative to conventional oxygen therapy that has not been evaluated in the emergency department (ED). We aimed to study its feasibility and efficacy in patients exhibiting acute respiratory failure presenting to the ED.

METHODS

Prospective, observational study in a university hospital's ED. Patients with acute respiratory failure requiring > 9 L/min oxygen or with ongoing clinical signs of respiratory distress despite oxygen therapy were included. The device of oxygen administration was then switched from non-rebreathing mask to HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning HFNC. Feasibility was assessed through caregivers' acceptance of the device in terms of practicality and perceived effect on the subjects, evaluated by questionnaire.

RESULTS

Seventeen subjects, median age 64 y (46-84.7 y), were studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC was associated with a significant decrease in both dyspnea scores: Borg scale from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1-5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min) to 25 breaths/min (21-28 breaths/min) (P < .001), and S(pO(2)) increased from 90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated and no adverse event was noted. Altogether, 76% of healthcare givers declared preferring HFNC, as compared to conventional oxygen therapy.

CONCLUSIONS

HFNC is possible in the ED, and it alleviated dyspnea and improved respiratory parameters in subjects with acute hypoxemic respiratory failure.

Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated.

Sim MA, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated. Anaesthesia. 2008;63(9):938-940. doi:10.1111/j.1365-2044.2008.05536.x

Oxygen is the commonest drug prescribed in hospitals. The inhaled concentration is altered by the administered oxygen flow rate, the characteristics of the delivery device and the patient's respiratory pattern. Using healthy volunteers we measured the inspired oxygen concentration achieved with different devices both at rest and when the breathing pattern of respiratory failure was simulated by binding the subjects' chests until the forced expiratory volume in 1 s was reduced by > 50% and the respiratory rate was > 25 breaths.min(-1). With this respiratory pattern, there was a statistically significant fall in F(I)o(2) while administering oxygen via a Hudson mask at 4 l.min(-1) (23.8% (95% CI 17.4-30.3%) reduction), 12 l.min(-1), humidified (17.8% (95% CI 8.8-26.7%) reduction) and 24 l.min(-1), humidified (12.2% (95% CI 5.0-19.3%) reduction). There was no statistically significant change with a nonrebreathing (reservoir) mask at 15 and 110 l.min(-1) or with a Vapotherm 2000i at 40 l.min(-1), humidified, via nasal prongs. We conclude that the F(I)o(2) delivered by high flow devices is unaffected when the breathing pattern of respiratory failure is simulated. The F(I)o(2) achieved at rest by a nonrebreathing mask (0.68) is less than that often quoted in the literature.

Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures.

Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011;39(6):1103-1110. doi:10.1177/0310057X1103900620

In this study, we evaluated the performance of a humidified nasal high-flow system (Optiflow, Fisher and Paykel Healthcare) by measuring delivered FiO, and airway pressures. Oxygraphy, capnography and measurement of airway pressures were performed through a hypopharyngeal catheter in healthy volunteers receiving Optiflow humidified nasal high flow therapy at rest and with exercise. The study was conducted in a non-clinical experimental setting. Ten healthy volunteers completed the study after giving informed written consent. Participants received a delivered oxygen fraction of 0.60 with gas flow rates of 10, 20, 30, 40 and 50 l/minute in random order FiO2, F(E)O2, F(E)CO2 and airway pressures were measured. Calculation of FiO2 from F(E)O2 and F(E)CO2 was later performed. Calculated FiO2 approached 0.60 as gas flow rates increased above 30 l/minute during nose breathing at rest. High peak inspiratory flow rates with exercise were associated with increased air entrainment. Hypopharyngeal pressure increased with increasing delivered gas flow rate. At 50 l/minute the system delivered a mean airway pressure of up to 7.1 cm H20. We believe that the high gas flow rates delivered by this system enable an accurate inspired oxygen fraction to be delivered. The positive mean airway pressure created by the high flow increases the efficacy of this system and may serve as a bridge to formal positive pressure systems.

Performance of six types of oxygen delivery devices at varying respiratory rates.

Wagstaff TA, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia. 2007;62(5):492-503. doi:10.1111/j.1365-2044.2007.05026.x

The administration of a known concentration of oxygen is an important part of routine care of the sick patient. Many devices are currently available. The actual concentration of oxygen that can be delivered by these devices can be affected by several factors, both from the patient as well as the device itself. Measuring the F(i)o(2) delivered to the lungs in vivo can be both difficult and potentially uncomfortable for the subjects. We constructed a model using a resuscitation manikin, a ventilator and a set of bellows to simulate ventilation. With this model we tested a series of devices - variable performance, fixed performance and high flow - at two fixed tidal volumes. The respiratory rate was increased and its effect on the oxygen concentration assessed. Variable performance systems such as the Hudson mask deliver a significantly reduced oxygen concentration at high respiratory rates. Fixed performance systems delivering 24-40% oxygen deliver appropriate oxygen concentrations across the range of respiratory rates, whereas those delivering 60% show a reduction in performance. High flow systems show no failure of performance at increased respiratory rates.

High flow nasal oxygen generates positive airway pressure in adult volunteers.

Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20(4):126-131. doi:10.1016/j.aucc.2007.08.001



INTRODUCTION

The use of non-invasive ventilation (NIV) as an alternative to intubation in respiratory failure is associated with better outcomes in certain conditions. NIV is often poorly tolerated by patients hence precipitating the need for invasive ventilation. High flow nasal (HFN) oxygen delivery is a potential alternative to NIV as it delivers air and oxygen via a humidified circuit at flows greater than those traditionally used with a nasal interface. BODY: Studies of paediatric patient using high flow nasal oxygen therapy have been shown to have similar efficacy as nasal continuous positive airway pressure (CPAP). Although the degree of positive pressure and the effect of different flow rates on positive pressure generation have not been well defined or studied in the adult intensive care population. St. Vincent's Health Human Research and Ethics Committee granted approval to this study and also awarded a $3000 grant. Volunteers were fitted with the Fisher & Paykel high flow nasal interface (RT034) and pharyngeal pressures were recorded with flows from 0 to 60L/min. Expiratory pressures with the mouth closed were higher than those with the mouth open and this was statistically significant (<0.001). Expiratory pressures were higher with the mouth closed and were statistically different (p<0.001). EPPs were higher amongst female subjects compared to male subjects and were statistically different between genders for both open (p<0.05) and closed (p<0.001) measurements.

CONCLUSION

This study has demonstrated that high flow nasal therapy is associated with the generation of significant positive airway pressure in volunteers. In conclusion there is a degree of CPAP generated with the HFN therapy, which is flow dependent and also dependent on whether the person is breathing with mouth open or closed.

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.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients.

Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107(6):998-1004. doi:10.1093/bja/aer265



BACKGROUND

High-flow nasal cannulae (HFNCs) create positive oropharyngeal airway pressure, but it is unclear how their use affects lung volume. Electrical impedance tomography allows the assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (P(aw)) and end-expiratory lung volume (EELV) and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate, dyspnoea, tidal volume, and oxygenation; and the interaction between BMI and EELV.

METHODS

Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, P(aw), ratio, respiratory rate, and modified Borg scores were recorded first on low-flow oxygen and then on HFNC.

RESULTS

A strong and significant correlation existed between P(aw) and end-expiratory lung impedance (EELI) (r=0.7, P<0.001). Compared with low-flow oxygen, HFNC significantly increased EELI by 25.6% [95% confidence interval (CI) 24.3, 26.9] and P(aw) by 3.0 cm H(2)O (95% CI 2.4, 3.7). Respiratory rate reduced by 3.4 bpm (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3), and ratio improved by 30.6 mm Hg (95% CI 17.9, 43.3). A trend towards HFNC improving subjective dyspnoea scoring (P=0.023) was found. Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (P<0.001).

CONCLUSIONS

This study suggests that HFNCs reduce respiratory rate and improve oxygenation by increasing both EELV and tidal volume and are most beneficial in patients with higher BMIs.

Failure of high-flow nasal cannula therapy may delay intubation and increase mortality.

Kang BJ, Koh Y, Lim CM, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015;41(4):623-632. doi:10.1007/s00134-015-3693-5



PURPOSE

Intubation in patients with respiratory failure can be avoided by high-flow nasal cannula (HFNC) use. However, it is unclear whether waiting until HFNC fails, which would delay intubation, has adverse effects. The present retrospective observational study assessed overall ICU mortality and other hospital outcomes of patients who received HFNC therapy that failed.

METHODS

All consecutive patients in one tertiary hospital who received HFNC therapy that failed and who then required intubation between January 2013 and March 2014 were enrolled and classified according to whether intubation started early (within 48 h) or late (at least 48 h) after commencing HFNC.

RESULTS

Of the 175 enrolled patients, 130 (74.3 %) and 45 (25.7 %) were intubated before and after 48 h of HFNC, respectively. The groups were similar in terms of most baseline characteristics. The early intubated patients had better overall ICU mortality (39.2 vs. 66.7 %; P = 0.001) than late intubated patients. A similar pattern was seen with extubation success (37.7 vs. 15.6 %; P = 0.006), ventilator weaning (55.4 vs. 28.9 %; P = 0.002), and ventilator-free days (8.6 ± 10.1 vs. 3.6 ± 7.5; P = 0.011). In propensity-adjusted and -matched analysis, early intubation was also associated with better overall ICU mortality [adjusted odds ratio (OR) = 0.317, P = 0.005; matched OR = 0.369, P = 0.046].

CONCLUSIONS

Failure of HFNC might cause delayed intubation and worse clinical outcomes in patients with respiratory failure. Large prospective and randomized controlled studies on HFNC failure are needed to draw a definitive conclusion.

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.

An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy.

Roca O, Caralt B, Messika J, et al. An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy. Am J Respir Crit Care Med. 2019;199(11):1368-1376. doi:10.1164/rccm.201803-0589OC

Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives: To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/FiO2 to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods: This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results: Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/FiO2 had a greater weight than respiratory rate. Conclusions: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).

Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates.

Mauri T, Alban L, Turrini C, et al. Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates. Intensive Care Med. 2017;43(10):1453-1463. doi:10.1007/s00134-017-4890-1



PURPOSE

Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients.

METHODS

A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure-time product (PTPPes), and lung volume, by electrical impedance tomography.

RESULTS

Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly.

CONCLUSIONS

In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.

Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study.

Mauri T, Carlesso E, Spinelli E, et al. Increasing support by nasal high flow acutely modifies the ROX index in hypoxemic patients: A physiologic study. J Crit Care. 2019;53:183-185. doi:10.1016/j.jcrc.2019.06.020

The ROX (Respiratory rate-OXygenation) index is an early predictor of failure of nasal high flow (NHF), with lower values indicating higher risk of intubation. We measured the ROX index at set flow rate of 30 and 60 l/min in 57 hypoxemic patients on NHF. Patients with increased ROX index values at higher flow (n = 40) showed worse baseline oxygenation, higher respiratory rate and lower ROX index in comparison to patients with unchanged or decreased ROX index values (n = 17). The ROX index variation between flows was correlated with the change in end expiratory lung volume. Set flow rate during NHF might impact the ROX index value.

Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome.

Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.003



BACKGROUND

ARDS is an important clinical problem. The definition of ARDS requires testing of arterial blood gas to define the ratio of Pao2 to Fio2 (Pao2/Fio2 ratio). However, many patients with ARDS do not undergo blood gas measurement, which may result in underdiagnosis of the condition. As a consequence, a method for estimating Pao2 on the basis of noninvasive measurements is desirable.

METHODS

Using data from three ARDS Network studies, we analyzed the enrollment arterial blood gas measurements to compare nonlinear with linear and log-linear imputation methods of estimating Pao2 from percent saturation of hemoglobin with oxygen as measured by pulse oximetry (Spo2). We compared mortality on the basis of various measured and imputed Pao2/Fio2 ratio cutoffs to ensure clinical equivalence.

RESULTS

We studied 1,184 patients, in 707 of whom the Spo2 ≤ 96%. Nonlinear imputation from the Spo2/Fio2 ratio resulted in lower error than linear or log-linear imputation (P < .001) for patients with Spo2 ≤ 96% but was equivalent to log-linear imputation in all patients. Ninety-day hospital mortality was 26% to 30%, depending on the Pao2/Fio2 ratio, whether nonlinearly imputed or measured. On multivariate regression, the association between imputed and measured Pao2 varied by use of vasopressors and Spo2.

CONCLUSIONS

A nonlinear equation more accurately imputes Pao2/Fio2 from Spo2/Fio2 than linear or log-linear equations, with similar observed hospital mortality depending on Spo2/Fio2 ratio vs measured Pao2/Fio2 ratios. While further refinement through prospective validation is indicated, a nonlinear imputation appears superior to prior approaches to imputation.

Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome.

Brown SM, Grissom CK, Moss M, et al. Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest. 2016;150(2):307-313. doi:10.1016/j.chest.2016.01.003



BACKGROUND

ARDS is an important clinical problem. The definition of ARDS requires testing of arterial blood gas to define the ratio of Pao2 to Fio2 (Pao2/Fio2 ratio). However, many patients with ARDS do not undergo blood gas measurement, which may result in underdiagnosis of the condition. As a consequence, a method for estimating Pao2 on the basis of noninvasive measurements is desirable.

METHODS

Using data from three ARDS Network studies, we analyzed the enrollment arterial blood gas measurements to compare nonlinear with linear and log-linear imputation methods of estimating Pao2 from percent saturation of hemoglobin with oxygen as measured by pulse oximetry (Spo2). We compared mortality on the basis of various measured and imputed Pao2/Fio2 ratio cutoffs to ensure clinical equivalence.

RESULTS

We studied 1,184 patients, in 707 of whom the Spo2 ≤ 96%. Nonlinear imputation from the Spo2/Fio2 ratio resulted in lower error than linear or log-linear imputation (P < .001) for patients with Spo2 ≤ 96% but was equivalent to log-linear imputation in all patients. Ninety-day hospital mortality was 26% to 30%, depending on the Pao2/Fio2 ratio, whether nonlinearly imputed or measured. On multivariate regression, the association between imputed and measured Pao2 varied by use of vasopressors and Spo2.

CONCLUSIONS

A nonlinear equation more accurately imputes Pao2/Fio2 from Spo2/Fio2 than linear or log-linear equations, with similar observed hospital mortality depending on Spo2/Fio2 ratio vs measured Pao2/Fio2 ratios. While further refinement through prospective validation is indicated, a nonlinear imputation appears superior to prior approaches to imputation.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

Rochwerg B, Granton D, Wang DX, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019;45(5):563-572. doi:10.1007/s00134-019-05590-5



BACKGROUND

This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure.

METHODS

We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods.

RESULTS

We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use.

CONCLUSION

In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

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