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Difference in PaO2/FiO2 between high-flow nasal cannula and Venturi mask in hypoxemic COVID-19 patients


The ratio between arterial blood partial pressure of oxygen and fraction of inspired oxygen (PaO2/FiO2) was largely used for grading and managing the respiratory failure in non-mechanically ventilated COVID-19. In these patients, the assessment of the true FiO2 in the inspired mixture may be difficult with consequent inaccuracies in PaO2/FiO2 assessment. In 30 severe COVID-19 patients, we observed that PaO2/FiO2 values measured immediately before and after the transition from high-flow nasal cannula (HFNC) to one commercially available Venturi mask O2 therapy were similar (bias mean value 0, standard deviation 23 mmHg). In COVID-19 patients recovering from respiratory failure, PaO2/FiO2 is not different whether measured with a commercially available Venturi mask or HFNC.


During the SARS-CoV-2 pandemic, the ratio between arterial blood partial pressure of oxygen and fraction of inspired oxygen in the inspired mixture (PaO2/FiO2, mmHg) was largely used for defining the severity of the respiratory failure and its progression, for deciding the appropriate respiratory support, and, consequently, for using specific pharmacological therapy [1]. Therefore, a careful assessment of PaO2/FiO2 is fundamental. As it is well known, PaO2/FiO2 is not the ideal variable for measuring the PO2 alveolar-arterial gradient because it does not consider PCO2 and its not linear relationship with FiO2 regardless of the alveolar-arterial gradient [2]. Moreover, PaO2/FiO2 was initially proposed in mechanically ventilated patients, where FiO2 is carefully measured. In non-mechanically ventilated patients, as patients in conventional O2 mask or high-flow nasal cannula (HFNC), the assessment of the true FiO2 in the inspired mixture may be problematic, specifically in dyspneic/tachypneic patients with high inspiratory peak flow or with the mouth breathing during HFNC [3, 4]. Therefore, PaO2/FiO2 values during the transition through the different methods of O2 delivery could lead to misinterpretation of the degree of respiratory dysfunction. For the above reasons, we decided to investigate whether the transitions from HFCN and Venturi mask (VM), or vice versa, alter PaO2/FiO2 values because of potential undetected differences in true FiO2.


Thirty consecutive patients admitted to our COVID-19 intensive care unit (ICU) because of severe respiratory failure due to SARS-CoV-2 infection and undergoing weaning from respiratory supports were included. As for internal protocol, after weaning from mechanical ventilation and SpO2 > 90% with FiO2 < 0.7 in HFNC (flow rate 60 L/min), the patients alternated HFNC and VM (FIAB S.p.A., model OS/60K, Florence, Italy) at the same FiO2 levels with a progressive de-escalating time scheme. Twenty minutes after the transition from HFNC to VM or vice versa, we collected respiratory rate (RR), mean arterial pressure, heart rate, FiO2, PaO2, the partial pressure of carbon dioxide (PaCO2), and pH in the arterial blood and calculated alveolar-arterial PO2 gradient (P(A-a)O2) [5]. To evaluate the differences between HFNC and VM, analysis of variance, linear regression analysis, and Bland-Altman method were used [6]. The study was approved by the ethical committee (658/2020/OSS*/AOUMO SIRER ID 417), and informed consent was obtained from participants.


Patients’ characteristics were detailed in Table 1. Twenty-nine patients received HFNC first and only one VM first. The PaO2/FiO2 measured in HFNC were like those measured in VM (Table 2) with a significant linear relationship (R2 = 0.51, p < 0.01). In the Bland-Altman analysis, the mean value and standard deviation of the bias were 0 and 23 mmHg (Fig. 1). The RR and PaCO2 values resulted to be different (p = 0.013 and p = 0.001) with RR higher and PaCO2 lower in VM compared to HFNC (Table 2). In patients previously treated with HFNC, PaCO2 was lower during VM in 25 patients (86.2%), and the difference was up to 5 mmHg in only 4 patients (13.8%).

Table 1 Clinical characteristics of the patients
Table 2 Blood gases values and vital signs in HFNC and VM
Fig. 1
figure 1

Bland and Altman diagram. The continuous line represents mean bias; the dashed lines represent 1.96 standard deviations. HFNC high-flow nasal cannula, VM Venturi mask


Our data indicate that after 20 min from HFNC to VM transition and vice versa, PaO2/FiO2 remain similar with only a small and not significant difference. Previous studies suggested that HFNC may improve oxygenation and decrease work of breathing compared to conventional O2 therapy [7,8,9]. In contrast with previous reports, our results may suggest that there may be an underestimation of FiO2 with Venturi device yielding overestimation of PaO2/FiO2 in contrast with the accurate delivery of FiO2 with HFNC. Anyway, in this specific population under these circumstances, both these two phenomena have clinically acceptable limits of agreement. Moreover, we observed that RR differed between the two methods despite the very short period of exposure (20 min). The main part of the sample transitioned to VM after having received HFNC, so it cannot exclude a possible carry-over effect for PaCO2 in this transition. Moreover, a possible carry-over effect cannot be excluded also for PaO2/FiO2 ratio. Rather than reducing work of breathing, the association of lower RR with a consensual increase of PaCO2 supports the hypothesis that HFNC, compared to VM, could improve oxygenation with less requirement of alveolar ventilation for maintaining PaO2 level. However, the low number of patients and the lack of assessment of the true FiO2 limit any further speculation on this point.

In conclusion, our study demonstrated that although in HFNC and VM the FiO2 is only estimated and may vary with the patient's respiratory pattern, PaO2/FiO2 measured with a VM may be considered a reliable parameter for respiratory dysfunction evaluation in severely hypoxemic patients during the transitions from different O2 delivery methods.

Availability of data and materials

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.



High-flow nasal cannula


Venturi mask


Intensive care unit


Respiratory rate

P(A-a)O2 :

Alveolar-arterial PO2 gradient


Median arterial pressure


Heart rate

PaO2/FiO2 :

Arterial blood partial pressure of oxygen and fraction of inspired oxygen


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Modena Covid-19 Working Group (MoCo19)

Intensive care unit: Massimo Girardis, Alberto Andreotti, Emanuela Biagioni, Filippo Bondi, Stefano Busani, Giovanni Chierego, Marzia Scotti, Lucia Serio, Annamaria Ghirardini, Marco Sita, Stefano De Julis, Lara Donno, Lorenzo Dall’Ara, Carlotta Farinelli, Laura Rinaldi, Ilaria Cavazzuti, Elena Ferrari, Irene Coloretti, Sophie Venturelli, Elena Munari, Martina Tosi, Erika Roat, Ilenia Gatto, and Caciagli Valeria

Immuno-Lab: Andrea Cossarizza, Caterina Bellinazzi, Rebecca Borella, Sara De Biasi, Anna De Gaetano, Lucia Fidanza, Lara Gibellini, Anna Iannone, Domenico Lo Tartaro, Marco Mattioli, Milena Nasi, Annamaria Paolini, and Marcello Pinti

Infectious Disease Unit: Cristina Mussini, Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, and Luca Corradi

Respiratory Diseases Unit: Enrico Clini, Roberto Tonelli, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Giulia Bruzzi, Chiara Nani, Fabiana Trentacosti, Pierluigi Donatelli, Maria Rosaria Pellegrino, Linda Manicardi, Antonio Moretti, Morgana Vermi, and Caterina Cerbone

Virology and Molecular Microbiology Unit: Monica Pecorari, William Gennari, Antonella Grottola, Giulia Fregni Serpini, and Mario Sarti



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GI, BE, VS, and GM designed the study, enrolled the patients, analyzed data, and wrote the paper. BS and CI reviewed and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ilenia Gatto.

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The study was approved by the ethical committee (658/2020/OSS*/AOUMO SIRER ID 417), and informed consent was obtained from participants.

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Gatto, I., Biagioni, E., Coloretti, I. et al. Difference in PaO2/FiO2 between high-flow nasal cannula and Venturi mask in hypoxemic COVID-19 patients. J Anesth Analg Crit Care 2, 23 (2022).

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