Full Citation: Perkins GD, Ji C, Connolly BA, et al. Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: The RECOVERY-RS randomized clinical trial. JAMA. Published online January 24, 2022. https://doi.org/10.1001/jama.2022.0028
Abstract Link: https://pubmed.ncbi.nlm.nih.gov/35072713/
Article Type: Randomized controlled trial
Ratings: Methods—3.5/5, Usefulness—4/5
Introduction
Background
Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended modalities for managing acute hypoxemic respiratory failure in COVID-19 patients. However, their effectiveness and safety remain unknown.
Objectives
Determine the effectiveness of CPAP or HFNO, compared with conventional oxygen therapy, in patients hospitalized with acute hypoxemic respiratory failure secondary to COVID-19.
Methods
Design and setting
A parallel group, adaptive, open-label, randomized clinical trial conducted in 48 acute care hospitals in the United Kingdom and Jersey.
Subjects
Hospitalized adults with known or suspected COVID-19-related acute hypoxemic respiratory failure (defined as having an oxygen saturation of ≤ 94% despite receiving a fraction of inspired oxygen of at least 0.40).
Intervention
CPAP or HFNO.
Comparison
Conventional oxygen therapy.
Outcomes
The primary outcome was a composite of tracheal intubation or mortality within 30 days of randomization. Secondary outcomes included tracheal intubation within 30 days, mortality within 30 days, time to tracheal intubation, duration of invasive mechanical ventilation, time to death, in-intensive care unit (ICU) mortality, in-hospital mortality, ICU admission, ICU length of stay, and hospital length of stay.
Main results
Of the 1278 participants randomized for the study, 1273 (CPAP 380, HFNO 418, control 475) were included, with primary outcome data available for 1260 (CPAP 377, HFNO 415, conventional oxygen 468).
For the primary outcome, CPAP demonstrated a statistically significant reduction in the composite outcome of tracheal intubation or mortality within 30 days (36.3% vs. 44.4%; − 8 [95% CI − 15 to − 1%], P = 0.03), whereas HFNO did not (44.3% vs. 45.1%; − 1% [95% CI − 8 to 6%], P = 0.83).
The secondary outcomes for the individual components of the primary outcome for the CPAP and HFNO intervention arms are presented in Tables 1 and 2, respectively.
Appraisal
Strengths
-
Pragmatic trial
-
Low number of patients lost to follow-up
-
Inverse probability weighting as secondary exploratory analysis used to correct for potential bias occurring from treatment group crossover
Limitations
-
Open-label
-
Escalation to tracheal intubation was not standardized
-
Time to tracheal intubation was longest in the CPAP arm, which may reflect a desire to delay tracheal intubation, potentially influencing outcomes
-
17.1% of participants experienced crossover between treatment groups
-
Early study termination prior to reaching the planned sample size
-
Trial may have been underpowered to compare CPAP and HFNO, and detect clinically important benefits of HFNO
Context
A systematic review and meta-analysis studying noninvasive oxygenation strategies in all cause hypoxemic respiratory failure identified a significant reduction in mortality and intubation with noninvasive positive pressure ventilation, as well as a significant reduction in intubation, but not mortality, with HFNO [1].
The HiFLo-Covid trial demonstrated a significant reduction in intubation and time to clinical recovery within 28 days with HFNO, relative to conventional oxygen therapy, in severe COVID-19 [2].
The HENIVOT trial found no statistically significant difference between helmet noninvasive ventilation and HFNO in the number of days free of respiratory support within 28 days in COVID-19-associated hypoxemia [3].
Local critical care physicians support considering the use of early CPAP in COVID-19-associated acute hypoxemic respiratory failure.
Bottom line
The RECOVERY-RS randomized trial identified a significant reduction for the composite outcome of tracheal intubation or mortality within 30 days when using CPAP in COVID-19-associated acute hypoxemic respiratory failure. The reduction in the primary outcome is primarily driven by the decreased tracheal intubation rates. Despite this benefit, the increased prevalence of adverse events with CPAP must be noted. In contrast, no significant benefit was seen with HFNO.
Based on the available evidence, we recommend considering CPAP early when managing COVID-19-associated acute hypoxemic respiratory failure [4]. HFNO can also be considered based on individual patient factors and location [4].
References
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. https://doi.org/10.1001/jama.2020.9524.
Ospina-Tascón GA, Calderón-Tapia LE, García AF, et al. Effect of high-flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID-19: a randomized clinical trial. JAMA. 2021;326(21):2161–71. https://doi.org/10.1001/jama.2021.20714.
Grieco DL, Menga LS, Cesarano M, et al. Effect of helmet noninvasive ventilation vs high-flow nasal oxygen on days free of respiratory support in patients with COVID-19 and moderate to severe hypoxemic respiratory failure: the HENIVOT randomized clinical trial. JAMA. 2021;325(17):1731–43. https://doi.org/10.1001/jama.2021.4682.
Zampieri FG, Ferreira JC. Defining optimal respiratory support for patients With COVID-19. JAMA. 2022. https://doi.org/10.1001/jama.2022.0067 (Published online January 24).
Acknowledgements
The authors would like to acknowledge Dr. Erin Rosenberg for providing the clinical perspective of a critical care physician for the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interests or sources of funding to declare.
Rights and permissions
About this article
Cite this article
Durr, K.M., Yadav, K. & Rosenberg, H. Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: The RECOVERY-RS randomized clinical trial. Can J Emerg Med 24, 582–584 (2022). https://doi.org/10.1007/s43678-022-00327-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43678-022-00327-8