Dr Swapnil Pawar March 3, 2022 212

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    NIV in COVID-19
    Dr Swapnil Pawar


Written by Dr Jose Chacko and Dr Swapnil Pawar

Current Guidelines – 

Available Evidence – 


Does CPAP or HFNO, compared with conventional oxygen therapy, reduce the need for tracheal intubation or mortality within 30 days in COVID-19-related acute respiratory failure?


The RECOVERY-RS trial was a 3-group, randomized clinical trial. The trial was conducted across 48 acute care hospitals in the UK and Jersey.

In effect, RECOVERY-RS represents two separate trials that compare CPAP and HFNO with a common control group of conventional oxygen therapy.

Allowed the hospital site to randomize patients to (1) CPAP, HFNO, or conventional oxygen therapy (on a 1:1:1 basis) or (2) a single intervention (CPAP or HFNO) or conventional oxygen therapy (on a 1:1 basis) depending on availability

Randomization was stratified by hospital site, sex, and age


Adult hospitalized patients (aged ≥18 years) with known or suspected COVID-19 with acute hypoxemic respiratory failure were eligible. Acute hypoxemic respiratory failure was defined as oxygen saturation of 94% with a FiO2 of 0.40 or more. The patients included were planned to undergo full support including invasive ventilation if they deteriorate.


Immediate intubation required

Only for end-of-life care



Conventional oxygen therapy was through a standard face mask or nasal cannula.

CPAP group had no positive inspiratory pressure. The choice of device choice, set up and titration of support was based on individual policies or clinician judgement. Intubation was based on clinician judgment. The crossover was defined as the alternate modality (CPAP or HFNO) for longer than 6 hours.

Sample size calculated based on a 15% incidence of the composite primary outcome of intubation or mortality within 30 d; assuming 5% reduction, power of 90%; 2-sided significance level of .05. Inverse probability weighting was carried out as a correction for crossover

A thousand patients were planned in each group; later the total sample size increased to 4002 due to uncertainty regarding event rates and the changing incidence of Covid-19

Analysis based on the intervention they were randomized to.


The trial was stopped early due to declining in Covid patients and a lack of continued funding after the recruitment of 1278 patients as against the projected 4002 patients.


Composite primary outcome

Secondary outcomes

Length of stay in the ICU

Length of stay in the hospital

An inverse probability weighting analysis that accounted for crossovers to the other treatment groups resulted in similar estimates

Post Hoc outcomes

The primary composite outcome CPAP vs. HFNC: 34.6% (91/263) vs. 44.3% (136/307) P = .02

Significantly in favour of CPAP

ICU, hospital mortality: no difference

ICU, hospital LOS: no difference

Exploratory outcomes

Adjusted analyses and the inverse probability weighting analysis were consistent with the primary analysis not statistically significant

Subgroup analysis

Age, sex, BMI, race, time of onset to randomization, FiO2 less than 0.6 vs. more

For HFNO, FiO2 >0.6 benefited compared to oxygen

Adverse events

CPAP: 34.2%

HFNC: 20.6%

Oxygen: 13.9%

Four of the serious adverse events were classified as probably or possibly linked to the trial intervention and all of these events occurred in the CPAP group (1 patient with surgical emphysema and pneumomediastinum, 2 patients with pneumothorax and pneumomediastinum, and 1 patient with vomiting requiring emergency tracheal intubation)


  • Did not attain projected sample size
  • Why reduced intubation rates alone with no reduction in mortality?
  • Outcomes only up to 30 days
  • No predefined criteria for intubation
  • Bias due to lack of blinding
  • Details of concomitant treatment modalities not available
  • No inspiratory support pressure – would this make a difference? What may be the optimal method of non-invasive respiratory support?
  • Would a combined approach be more efficacious?




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