Introduction

Non-invasive respiratory strategies (NIRS) such as continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) are potentially attractive methods for avoiding invasive mechanical ventilation (IMV) and its inherent risks in COVID-19 patients. As there is lack of evidence supporting the use of CPAP and HFNO in COVID-19 patient, we can find a significant variability both in international guidelines and clinical practice [1,2].

Method

The RECOVERY-RS trial [3] tried to evaluate the clinical effectiveness of CPAP or HFNO compared to standard oxygen therapy in Covid-19 hospitalized patients with acute hypoxemic respiratory failure. In this multicenter RCT conducted across 48 hospitals in UK, 1272 Covid-19 patients with an oxygen saturation of 94% or less despite receiving a fraction of inspired oxygen (FIO2) of at least 0.40 were randomized to receive CPAP, HFNO, or conventional oxygen therapy (that represented a common shared control group). The treating clinician and the unavailability of CPAP or HFNO could precluded contraindication to randomization to a specific trial group. In addition, device choice, setup, titration, treatment discontinuation and orotracheal intubation (IOT) were decided by the treating clinician. The primary outcome was a composite outcome of IOT or mortality within 30 days of randomization.

Results

Concerning the baseline characteristic of participants, 380 patients were randomized to receive CPAP, 418 HFNO and 475 oxygen therapy respectively. The medium PaO2/FiO2 ratio ranged from 112.5 to 115. Interestingly, randomization was obtained during early phases of covid-19, nine days after symptoms onset.  No data about radiological features were available.

For the comparison of CPAP vs standard oxygen therapy, the primary outcome occurred in 36,3% of the patients randomized in CPAP group vs 44,4% of the participants enrolled in standard oxygen therapy group. No statistical difference was found comparing HFNO group vs conventional oxygen therapy group: primary outcome was reached in 44,3% vs 45,1%, respectively.

Interestingly, the incidence of IOT in CPAP group was lower compared to conventional oxygen therapy group (33,4% vs 41,3% respectively) while mortality rate was similar in the two study groups (16,7% vs 19%). A post hoc analysis performed to compare CPAP vs HFNO demonstrated that primary outcome occurred in 34.6% of participant enrolled in CPAP group (91/263) vs 44.3% (136/307) of patients enrolled in HFNO group.

To better describe the CPAP treatment, the authors report that the medium positive end-expiratory pressure was 8.3 cmH20 in the CPAP group and specify that 38.7% of these patients received CPAP trough a non-invasive ventilation machine set up for CPAP.

Conclusion

An initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality in patients with Covid-19 acute hypoxemic respiratory failure compared to conventional oxygen therapy.

Food for thought

• The lack of standardized IOT criteria

In our opinion, one of the major study limitations was that IOT criteria were not standardised, especially considering that IOT is part of the composite outcome. Gas exchange was similar between the three groups (89 vs 75 vs 76 in CPAP, HFNO and conventional oxygen therapy group respectively). To notice, prior to IOT, respiratory rate seems to be higher in CPAP vs conventional oxygen therapy group vs HFNO group (34/min vs 30/min vs 28/min).

• The lack of radiological data

The medical community’s debate about ventilatory treatment of patients with Covid 19 respiratory failure has been characterized by two “main” positions: the first, which argues that mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU [4]; and the second, which identifies two different "phenotypes": type L (Low elastance and high compliance) and type H (High elastance and low compliance) [5]. According to this theory, the L phenotype, characterized by ground-glass densities on CT scan, would benefit (at least at the beginning) from NIRS (HFNO, CPAP or NIV) while the H phenotype, characterized by a remarkable increase in lung weight (due to consolidation) on the CT scan, would probably require an ARDS-like ventilatory management.   

In conclusion, radiological pattern detected on CT scan could help to describe the phenotype of covid-19 patients and consequently guide the physician to appropriate respiratory strategy. Probably, radiological characteristic of this population could help to obtain information about the appropriate NIRS for both phenotypes.

• The CPAP mode

CPAP was delivered by non-invasive ventilation device set on “CPAP mode” in 38,7% of patients by CPAP device in 45,5% of patients. Mean CPAP values was 8,3 cmH20. Unfortunately, no data about interfaces were available. The lack of standardization of the device, set up and interfaces of CPAP makes stronger the study results (the reduction of the primary outcome of CPAP vs conventional oxygen therapy). On the other hand, considering the conclusions of the study, the heterogeneity of the modalities used can confuse the clinician when he/she choose CPAP device, setting and interface.

• The IOT time delay of CPAP group

In all the randomization groups most of the patients who meet the primary outcome were intubated (126/137 and 147/158 comparing CPAP vs Standard Oxygen therapy; 170/184 and 153/166 comparing HFNO vs Standard Oxygen therapy).  The authors emphasized that IOT occurred later in CPAP group compared to Standard Oxygen therapy group (p = 0.01). No statistical difference on mortality rate was found comparing CPAP vs Standard Oxygen therapy.

Previous data, concerning the use of NIV on “de novo” respiratory failure and mild to severe ARDS, showed that NIRS failure and IOT delay were associated with higher mortality rate (6, 7). These results seem to be unconfirmed in this large court of patient affected by Covid-19 acute respiratory distress syndrome (C-ARDS) suggesting that the respiratory management (such as optimal timing and threshold of IOT) used to support patients affected by “de novo” respiratory failure cannot be applied entirely to C-ARDS.

Bibliografia

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