Non-invasive respiratory support in SARS-CoV-2 related acute respiratory distress syndrome: when is it most appropriate to start treatment?

Abstract

Background: Acute respiratory distress syndrome (ARDS) is one of the most severe complications of SARS-CoV-2 infection. Non-Invasive Respiratory Support (NRS) as Continuous Positive Airway Pressure (CPAP) and/or Non-Invasive Ventilation (NIV) has been proven as effective in the management of SARS-CoV-2-related ARDS. However, the most appropriate timing for start NRS is unknown.

Methods: We conducted a prospective pilot study including all consecutive patients who developed moderate SARS-CoV-2-related ARDS during hospitalization. Patients were randomly divided into two intervention groups according to ARDS severity (assessed by PaO₂/FiO₂-P/F) at NRS beginning: group A started CPAP/NIV when P/F was ≤ 200 and group B started CPAP/NIV when P/F was ≤ 150. Eligible patients who did not give their consent to CPAP/NIV until the severe stage of ARDS and started non-invasive treatment when P/F ≤ 100 (group C) was added. The considered outcomes were in-hospital mortality, oro-tracheal intubation (OTI) and days of hospitalization.

Results: Among 146 eligible patients, 29 underwent CPAP/NIV when P/F was ≤ 200 (Group A), 68 when P/F was ≤ 150 (Group B) and 31 patients agreed to non-invasive treatment only when P/F was ≤ 100 (Group C). Starting NRS at P/F level between 151 and 200 did not results in significant differences in the outcomes as compared to treatment starting with P/F ranging 101-150. Conversely, patients undergone CPAP/NIV in a moderate stage (P/F 101-200) had a significantly lower in-hospital mortality rate (13.4 vs. 29.0%, p = 0.044) and hospitalization length (14 vs. 15 days, p = 0.038) than those in the severe stage (P/F ≤ 100). Age and need for continuous ventilation were independent predictors of CPAP/NIV failure.

Conclusions: Starting CPAP/NIV in patients with SARS-CoV-2-related ARDS in moderate stage (100 > P/F ≤ 200) is associated to a reduction of both in-hospital mortality and hospitalization length compared to the severe stage (P/F ≤ 100). Starting CPAP/NIV with a P/F > 150 does not appear to be of clinical utility.

Keywords: ARDS; COVID-19; CPAP; NIV; SARS-CoV-2.

Fig. 1

Study design: Group A started CPAP/NIV when P/F fell below 200, Group B underwent CPAP/NIV when P/F fell below 150. Group C derives from patients initially excluded from the study for refusal of non-invasive treatment and who subsequently initiated treatment with CPAP/NIV in a severe stage of ARDS (P/F ≤ 100). CPAP Continuous Positive Airway Pressure, NIV Non-Invasive Ventilation, P/F PaO₂/FiO₂ rate

Fig. 2

Flow chart of evaluated SARS-CoV-2 infected patients. CPAP Continuous Positive Airway Pressure, NIV Non-Invasive Ventilation, P/F PaO₂/FiO₂ rate

Fig. 3

Above: Kaplan–Meier curves related to the analysis of mortality rates (a) and overall oro-tracheal intubation (OTI, b) among patients undergoing treatment with CPAP/NIV with a P/F between 151 and 200 (group A) and patients who initiated the treatment with a P/F between 101 and 150 (group B). Below: Kaplan–Meier curves related to the analysis of mortality (c) and OTI (d) rates among patients undergone CPAP/NIV in a moderate degree of respiratory distress (group A + B, P/F 101–200) and patients referred for treatment in a severe degree of respiratory distress (group C, P/F ≤ 100)

Fig. 4

Proposed timing for start CPAP/NIV to maximize results to be evaluated in future powered studies. ARDS Acute Respiratory Distress Syndrome, CPAP Continuous Positive Airway Pressure, NIV Non-Invasive Ventilation, OTI oro-tracheal intubation, P/F PaO2/FiO2 rate; VILI Ventilator Induced Lung Injury