Letter to the Editor
Systematic reviews comparing the effect of high-flow nasal treatment (HFNT) to conventional oxygen therapy (COT) or noninvasive ventilation (NIV) have focused on major clinical outcomes (i.e., endotracheal intubation, mortality) [1‐3]. None have explored weaker outcomes that may nonetheless be important from the patient’s perspective, yet physiopathological mechanisms suggest that the HFNT may provide some advantage in this regard [4, 5]. We therefore systematically reviewed all randomized (RCTs) and crossover trials enrolling patients either post-extubation or during acute respiratory failure (ARF), comparing HFNT to COT or NIV and reporting data about dyspnea, comfort, and respiratory rate (RR) (PROSPERO CRD42019119536).
Full search strategy, detailed study methods, reference lists, and risk of bias assessments are reported in Additional file 1.
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Twenty-four relevant studies were identified and included: for patients post-extubation, ten RCTs and one crossover trial and, for patients in ARF, eight RCTs and five crossover trials.
The summary of our findings is presented in the Table 1. More studies compared the effects of HNFT vs COT rather than vs NIV. Overall, there seems to be a trend showing that HFNT is probably not inferior to COT in most studies and perhaps better than NIV in terms of dyspnea, comfort, and decreasing of RR in some studies.
Table 1
Summary of findings in studies of the HFNT with regard to dyspnea, comfort, and respiratory rate
Study | Type | Design | Intervention (N) | Control (N) | Treatment methods | Measurement method | Dyspnea | Comfort | Respiratory rate |
|---|---|---|---|---|---|---|---|---|---|
Bell N. [6]
Emerg Med Australas 2015
| AHRF | RCT | HFNT (48) | COT (52) | HFNT: flow 50 L/m, FiO2 30% titrated to SpO2 95% COT: discretion of the treating physician | Dyspnea: Borg Scale Comfort: Likert Scale | HFNT§ | HFNT§ (1 h) | HFNT§ (2 h) |
Frat J.P. [7]
N Engl J Med 2015
| AHRF | RCT | HFNT (106) | COT (94) NIV (110) | HFNT: flow 50 L/m, FiO2 100% then titrated to SpO2 92% COT: O2 titrated to SpO2 92% NIV: PSV PEEP from 2 up to 10 fiO2 adjusted to SpO2 92% | Dyspnea: Likert Scale Comfort: VAS | HFNT§ | HFNT§ | HFNT§ (1 h) |
Lemiale V. [8]
Crit Care 2015
| AHRF (Immunocompromised) | RCT | HFNT (52) | COT (52) | HFNT: flow from 40 up to 50 L/m, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: VAS Comfort: VAS | NS | NS | NS |
Jones P.G. [9]
Respir Care 2016
| AHRF | RCT | HFNT (172) | COT (150) | HFNT: flow 40 L/m, 37 °C, FiO2 28% COT: FiO2 titrated to clinical needs | Dyspnea: Survey questions Comfort: Survey questions | NS | Overall comfort: NS “Dry my nose”: HFNT§ “In future I prefer”: COT§ “This method is worst”: HFNT§ | NS |
Doshi P. [10]
Ann Emergency Med 2017
| AHRF | RCT | HFNT (104) | NIV (112) | HFNT: flow from 35 L/m up to 40 L/m, T° between 35 and 37 °C NIV: IPAP from 10 up to 20 cmH20, EPAP from 5 up to 10 cmH20, FiO2 100% | Dyspnea: Borg Scale Comfort: NA | NA | NA | NA |
Makdee O. [11]
Ann Emergency Med 2017
| AHRF (CPE) | RCT | HFNT (63) | COT (65) | HFNT: flow from 35 up to 60 L/m, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: VAS Comfort: NA | NS | NA | HFNT§ (15, 30, 60 min) |
Azoulay E. [12]
JAMA 2018
| AHRF (Immunocompromised) | RCT | HFNT (388) | COT (388) | HFNT: flow 50 L/min, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: Dyspnea Score Comfort: VAS | NS | NS | HFNC§ (6 h) |
Spoletini G. [13]
J Crit Care 2018
| AHRF (On NIV) | RCT | HFNT (23) | COT (24) | HFNT: flow 35 L/m, FiO2 titrated to SpO2 92% (hypoxic) or to 88–92%(hypercapnic) COT: flow adjusted to maintain the same SpO2 | Dyspnea: Borg Scale Comfort: VAS | NS | HFNT§ | NS |
Cuquemelle E. [14]
Respir Care 2012
| AHRF | Crossover | HFNT (37) | COT (37) | HFNT: flow 40 L/m, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: NA Comfort: Dryness | NA | HFNT§ | NA |
Schwabbauer N. [15]
BMC Anesthesiol 2014
| AHRF | Crossover | HFNT (14) | COT (14) NIV (14) | HFNT: flow 55 L/m, FiO2 60% COT: Venturi mask FiO2 60% NIV: PSV FiO2 60% PEEP 5 cmH20 PS 6-8 ml/kg PBW | Dyspnea: Borg Scale Comfort: NRS | HFNT vs. COT HFNT§ vs. NIV | HFNT vs. COT HFNT§ vs. NIV | HFNT vs. COT HFNT vs. NIV COT vs. NIV§ |
Vargas F. [16]
Respir Care 2015
| AHRF | Crossover | HFNT (n = 12) | COT (12) CPAP (12) | HFNT: flow 60 L/m, T 37 °C, FiO2 same as COT COT: O2 titrated to SpO2 90% CPAP: 5 cmH20 FiO2 same as COT | Dyspnea: Dyspnea Score Comfort: NRS | NS | NS | HFNT§ vs. COT HFNT vs. CPAP |
Mauri T. [17]
Am J Respir Crit Care Med 2017
| AHRF | Crossover | HFNT (15) | COT (15) | HFNT: flow 40 L/m, FiO2 titrated to SpO2 90–95% COT: Airvo2 face mask 12 L/min same FiO2 | Dyspnea: DeltaPes Comfort: NA | HFNT§ | NA | HFNT§ |
Sklar M.C. [18]
Ann Intensive Care 2018
| ARF (Exacerbation of cystic fibrosis) | Crossover | HFNT (15) | NIV (15) | HFNT: flow 55 L/m, T° 34 or 37 °C FiO2 titrated to SpO2 92% NIV: FiO2 titrated to SpO2 92%, setting as previously adjusted | Dyspnea: VAS Comfort: VAS | NS | NS | NS |
Parke R. [19]
Br J Anaesth 2013
| Post-extubation (Cardiac surgery) | RCT | HFNT (169) | COT (171) | HFNT: flow 45 L/m, FiO2 titrated to SpO2 93% COT: O2 titrated to SpO2 93% | Dyspnea: NA Comfort: NRS | NA | HFNT§ | NA |
Maggiore S.M. [20]
Am J Respir Crit Care Med 2014
| Post-extubation | RCT | HFNT (53) | COT (52) | HFNT: flow 50 L/m, FiO2 titrated to SpO2 92–98% (hypoxic) or to 88–95%(hypercapnic) COT: O2 titrated to SpO2 92–98% (hypoxic) or 88–95%(hypercapnic) | Dyspnea: NA Comfort: NRS | NA | Interface: HFNT§ (from 12 h) Dryness: HFNT§ (from 24 h) | HFNT§ (from 1 h) |
Corley A. [21]
Intensive Care Med 2015
| Post-extubation (Cardiac) | RCT | HFNT (81) | COT (74) | HFNT: flow 35 up to 50 L/min, T 37 °C, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: Borg Scale Comfort: NA | COT§ (8 h) | NA | NS |
Stephan F. [22]
JAMA 2015
| Post-extubation (Cardiac) | RCT | HFNT (414) | NIV (416) | HFNT: flow 50 L/m, FiO2 titrated to SpO2 92–98% NIV: PEEP and PS adjusted to RR < 25/min and TV 8 ml/kg, FiO2 SpO2 92–98% | Dyspnea: Dyspnea Score Comfort: NRS | NS | NS | HFNT§(1 h, 1 day, 2 days, 3 days) |
Futier E. [23]
Intensive Care Med 2016
| Post-extubation (Abdominal or thoracic) | RCT | HFNT (108) | COT (112) | HFNT: flow 50–60 L/m, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: NA Comfort: NRS | NA | NS | NA |
Hernandez G. (a) [24]
JAMA 2016
| Post-extubation (Low-risk extubation failure) | RCT | HFNT (264) | COT (263) | HFNT: flow 10 L/m titrated in 5 L step until discomfort, FiO2 to SpO2 92%, T 37 °C COT: O2 titrated to SpO2 92% | Dyspnea: NA Comfort: NA | NA | NA | NA |
Hernandez G. (b) [25]
JAMA 2016
| Post-extubation (High-risk extubation failure) | RCT | HFNT (290) | NIV (314) | HFNT: flow 10 L/m titrated in 5 L step until discomfort, FiO2 to SpO2 92%, T 37 °C NIV: PEEP and PS adjusted to RR 25/min, SpO2 92%, pH 7.35 | Dyspnea: NA Comfort: NA | NA | NA | NA |
Fernandez R. [26]
Ann Intensive Care 2017
| Post-extubation (High-risk extubation failure) | RCT | HFNT (78) | COT (77) | HFNT: flow 40 L/min (adjusted on tolerance), T 37 or 34 °C, FiO2 titrated to SpO2 92–95% COT: O2 titrated to SpO2 92–95% | Dyspnea: NA Comfort: NA | NA | NA | NA |
Yu Y. [27]
Can Respir J 2017
| Post-extubation (Thoracic) | RCT | HFNT (56) | COT (54) | HFNT: flow from 35 to 60 L/m, FiO2 titrated to SpO2 95% COT: O2 titrated to SpO2 95% | Dyspnea: NA Comfort: Rates of throat/nasal pain | NA | HFNT§ | HFNT§ (1 h, 2 h, 6 h, 24 h, 48 h, 72 h) |
Song H.Z. [28]
Clinics (Sao Paulo) 2017
| post-extubation | RCT | HFNT (30) | COT (30) | HFNT: flow 60 L/m, FiO2 titrated to SpO2 94–98% (hypoxic) or to 88–92% (hypercapnic) COT: O2 titrated to SpO2 94–98% (hypoxic) or 88–92%(hypercapnic) | Dyspnea: NA Comfort: VAS | NA | HFNT§ (interface) HFNT§ (dryness) | HFNT§ |
Rittayamai N. [29]
Respir Care 2014
| post-extubation | Crossover | HFNT (17) | COT (17) | HFNT: flow 35 L/m, FiO2 titrated to SpO2 94% COT: O2 titrated to SpO2 94% | Dyspnea: VAS Comfort: VAS | HFNT§ (10, 15, 30 min) | NS | HFNT§ (5, 10, 15, 30 min) |
Heterogeneity in case-mix, the tools used for outcome assessment and measurement time-points precluded performance of meta-analysis. Neither patients nor treating clinicians were blinded to the intervention in any of the trials, introducing a high risk of detection bias. Differences in HFNT settings (i.e., flow and temperature) and a lack of full description for weaning criteria or protocol may have also contributed to the diversity in findings with regard to comfort and dyspnea.
In this analysis of the literature, the use of HFNT during ARF or post-extubation seems to be not clearly associated with improvements in comfort, dyspnea, and RR since findings from the most recent available evidence were inconsistent. However, in this regard, HFNT does not seem inferior to either COT or NIV. Future research should be focused in assessing patient-reported outcomes using appropriate standardized and validated measures in order to investigate the comparative effectiveness of the different respiratory support strategies.
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Acknowledgements
We would like to thank Dr. Filippo Sanfilippo for his help in registering the manuscript to PROSPERO.
Funding
None.
Availability of data and materials
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
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Not applicable.
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Not applicable.
Competing interests
Cesare Gregoretti received fees for consultancies or lectures from Orion Pharma, ResMed, Medtronic, Philips, Air Liquide and EOVE, and travel cost reimbursement from Fisher & Paykel. All other authors declared that they have no competing interests.
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