Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study

Abstract

Background: in COVID-19 acute respiratory failure, the effects of CPAP and FiO₂ on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO₂ delivered via oxygen masks.

Methods: In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO₂) and Venturi mask (FiO₂ 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics.

Results: We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH₂O, p < 0.01). However, Helmet's pressure decreased by a comparable amount during inspiration (- 3.1 ± 1.0 cmH₂O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from - 4.5 to + 6.1 cmH₂O, and from - 5.8 to + 5.7 cmH₂O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO₂ decreased from NRB to Helmet-CPAP with FiO₂ 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet's FiO₂ 0.9, PaO₂ increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO₂ fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81).

Conclusions: In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO₂ provide better oxygenation with lower respiratory effort. Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517 .

Keywords: COVID-19; Gas-exchange; Helmet-CPAP; Hemodynamics; Lung stress; Non-rebreather mask; Respiratory effort; Respiratory failure; Venturi mask.

Fig. 1

Experimental procedure. A: Enrolment flowchart. Of note, 12 of the 28 COVID-19 patients were recruited prior to trial registration, but with ethics approval; B: experimental equipment and monitoring of (1) Helmet’s pressure (P_aw) and (2) esophageal pressure (P_es) through OptiVent^™ monitor, (3) arterial blood gases (ABG) through radial line, (4) blood pressure (BP), cardiac output (CO) and heart rate (HR) through CNAP^® monitor consisting of a finger cuff and a brachial cuff; Panel C: experimental protocol

Fig. 2

Effects of positive pressure on respiratory effort and lung stress. Differences in respiratory effort (A), dynamic B, static C and total lung stress D between NRB and Helmet-CPAP in COVID-19 patients and Healthy subjects. Of note, measurement of airway pressure was missing in one patientBlack dots: single patients; Red bars: mean values; NRB Non-rebreather mask

Fig. 3

Changes in PaO₂ and DO₂ with positive pressure and FiO₂. Changes in PaO₂ A and DO₂ B between steps in COVID-19 patients; The overall p value for the change in PaO₂ between the five steps was < 0.01 (not shown). Black dots: single patients; Boxplots: medians and interquartile ranges; PaO₂ arterial oxygen tension. NRB Non-rebreather mask. DO₂ oxygen delivery

Fig. 4

Relationship between oxygenation and respiratory effort. A: relationship between PaO₂ during VM, and the change in respiratory effort from VM to NRB (n = 15): only in patients with PaO₂ < 60 mmHg (n = 8, red dots), a strong, significant relationship was found. B: relationship between PaO₂ and respiratory effort with oxygen masks (NRB and, when available, VM); PaO₂: arterial oxygen tension. NRB Non-rebreather mask, VM Venturi mask, AIC Akaike information criterion