key: cord-1026238-ce8owcjp
authors: Lebret, Marius; Fresnel, Emeline; Prieur, Guillaume; Quieffin, Jean; Dupuis, Johan; Lamia, Bouchra; Combret, Yann; Medrinal, Clément
title: High O(2) Flow Rates Required to Achieve Acceptable FiO(2) in CPAP-Treated Patients With Severe Covid-19: A Clinically Based Bench Study
date: 2021-09-01
journal: Arch Bronconeumol
DOI: 10.1016/j.arbr.2021.04.013
sha: f276fbc634e1549279cac6b9c28dce8c88d46f61
doc_id: 1026238
cord_uid: ce8owcjp

nan

while the remaining consolidation showed early homogeneous enhancement (<6 s) and delayed washout (>1 min) (Fig. 1B-F) . In view of these findings, we decided to biopsy the first of these areas with a 22 G fine needle; it was reported as alveolar metastasis of pancreatic adenocarcinoma (Fig. 1G) . Because the rest of the consolidation showed suggestive characteristics of a pneumonia process, we decided to perform fiberoptic bronchoscopy; samples obtained showed a fungal infection (Fig. 1H) .

In our patient we were able to differentiate between pneumonia and metastasis, as she presented pre-existing pulmonary consolidation containing a hypoechoic area. On contrast-enhanced ultrasound, the consolidation showed late homogeneous uptake with delayed washout, with the exception of the central and peripheral areas that showed late enhancement but early washout, suggestive of malignancy. This enhancement pattern also helped guide the percutaneous biopsy to the most suspicious target area to improve the diagnostic yield of the samples collected.

Ultrasound-guided biopsy is an alternative to CT-guided biopsy for peripheral or pleural lung lesions 1,3 and achieves a similar diagnostic effectiveness and yield as CT 5 . Additionally, ultrasoundguided percutaneous procedures offer certain advantages, such as real-time monitoring of the procedure, absence of radiation, lower costs and duration of the procedure, and the complication rates are similar to or lower than with CT-guided biopsy 1,2 . In many cases, contrast-enhanced chest ultrasound helps clarify the nature of the lesion under study and, if necessary, guides the biopsy needle towards areas of interest, avoiding necrotic foci 1,2,6 and targeting areas with a greater suspicion of malignancy, as in the case presented.

Se requieren altos índices de flujo de O2 para alcanzar una FiO2 aceptable en los pacientes con covid-19 tratados con CPAP: un estudio experimental basado en la clínica Dear Editor, During the Covid-19 pandemic, a lack of ventilatory equipment in intensive care units (ICU), or patient comorbidities meant that some patients received non invasive, continuous positive airway pressure (CPAP), with the highest fraction of inspired oxygen (FiO2) as a ceiling treatment. [1] [2] [3] In Le Havre hospital (France), between September and December 2020, around 30 patients were treated with bilevel home devices in CPAP mode using vented oronasal masks. In contrast with bench studies that reported high FiO 2 with oxygen flow rates < 30 L/min in optimal experimental conditions (i.e., low minute ventilation, good pulmonary compliance and no leakage), 4,5 many patients required O 2 flow rates > 70 L/min to maintain oxygen saturation (SpO 2 ) ≥ 90%. We hypothesised that due to the high respiratory demand of patients with severe Covid-19, a high O 2 flow rate would be required to reach adequate pressure levels with CPAP, thereby substantially increasing the oxygen flow rate needed to achieve a high FiO 2 . We carried out a bench study to measure the oxygen flow rates needed to reach high FiO 2 levels, using a pulmonary model that reproduced the characteristics of patients with severe Covid-19.

First, we extracted clinical data from 10 consecutive patients who were included in an ongoing clinical trial (EURO-CPAP CT2220141 approved by our institutional review board) from the CPAP built-in software. This case series is presented for descriptive purposes to illustrate our hypothesis. Then, we performed several bench experiments. We used a CPAP device (AirSense 10 AutoSet, ResMed, San Diego, CA, USA) set at 10 cmH 2 O, connected to an artificial lung (ASL 5000, Ingmar Medical, Pittsburgh, PA, USA). A low-resistance antibacterial filter (Clear-Guard, Intersurgical, Wokingham, UK), an oxygen inlet connector, a 15 mm single limb circuit, a Whisper Swivel II Exhalation port (Philips Respironics, Murrysville, PA, USA) that simulated intentional leaks, and the artificial lung were placed in series and connected to the CPAP device. A standard 4-mm diameter leak port was placed between the exhalation port and the artificial lung to mimic unintentional leakage. Oxygen was delivered into the system using two O 2 flow meters (EASY MED-O 2 , Air Liquide Healthcare, Paris, France) that could both deliver up to 50 L/min. Three different mechanical lung conditions were simulated by modulating the resistance (R) and the compliance (C) of the artificial lung, corresponding to the following experimental models:

A. Normal: R = 5 cmH 2 O/l s and C = 60 ml/cmH 2 O. B. Restrictive: R = 5 cmH 2 O/l s and C = 30 ml/cmH 2 O. C. Normal with by-pass leak using a T-connector as recommended to reduce the risk of droplet aerosolization. 6 Each model was run at breathing frequencies of 22, 30 and 35 cycles per minute (cpm), associated with inspiratory airway pressure drops of 2.5-6 cmH 2 O at 100 ms (P0.1) to reach tidal volumes of around 600 ml. The values of the inspiratory effort settings chosen for the simulation in the ASL5000 were based on pub- Fig. 1 . Dose-response relationship between oxygen (O2) flow rates delivered into the circuit, and fraction of inspired oxygen (FiO2) as a function of respiratory rate, presence/absence of non-intentional leakage, lung mechanics and leak port locations. Each Plot represents the mean FiO2 of the 10 cycles analysed. For each FiO2, the standard deviation was systematically below 0.3 and is therefore not represented on the graph. Panel A displays the results for the conventional intentional leak model, in which the unintentional leakage port was placed in series between the exhalation valve (intentional leak port) and the ASL 5000. Panel B displays the results for the same model as in panel A, but with restrictive lung mechanics. Panel C displays the results for by-pass leakage ports using an antibacterial filter between the ASL 5000 and both intentional and non-intentional leak ports. The blue lines represent the relationship between O2 flow and FiO2 without unintentional leaks, and the green lines represent the relationship between O2 flow and Fi2O with unintentional leaks. lished clinical values. [7] [8] [9] [10] [11] Each condition was run with and without unintentional leakage. FiO 2 was measured with 5, 15, 30, 50, 60 and 80 L/min of O 2 , and the experiment was stopped when 100% FiO 2 was reached. The sensor used was a paramagnetic oxygen transducer located in the ASL 5000 piston chamber which allowed a fast measurement with a response time below 350 ms. Ten respiratory cycles were analysed after the FiO 2 had reached an asymptote for each model at each O 2 flow rate. Normality and homogeneity were assessed using Shapiro-Wilk and Levene tests, respectively. Welch's ANOVA was used to compare respiratory rates at each O 2 flow rate. A Games-Howell post-hoc procedure was applied for multiple comparisons, with 22 cpm as the reference condition. Significance was set at 0.05. Statistical analysis was performed using IBM SPSS Statistics V25. Data from 10 consecutive patients with Covid-19 treated with CPAP and O 2 are presented in Table 1 . Six patients needed O 2 flow rates ≥ 50 L/min to maintain SpO 2 > 90%. Minimum O 2 flow rate was 15 L/min. All patients had severe infection (i.e., PaO 2 /FiO 2 ratio ≤ 150 at CPAP initiation). Fig. 1 shows the relationship between the O 2 flow rate delivered and the resulting FiO 2 in the simulation. Without unintentional leaks, a flow rate of at least 30 L/min was necessary to reach FiO 2 > 95%. FiO 2 differed significantly for each respiratory rate at each O 2 flow rate with and without unintentional leaks (p < 0.001). With unintentional leaks, O 2 flow rates of up to 80 l/min were required to reach 100% FiO 2 ( Fig. 1A-C) .

The results of this experimental bench study confirmed our clinical observation that high O 2 flow rates are required to achieve a high FiO 2 in patients with severe Covid-19 using CPAP and vented masks. An O2 flow rate of at least 30 L/min, and up to 80 L/min, was required to achieve 100% FiO2 for all three experimental models. Reduced compliance and unintentional leakage dramatically reduced FiO 2 . The arbitrary compliance of 30 ml/cmH 2 O used in model B is similar to that of patients with severe COVID-19. 12 Such a low level of compliance would reduce the FiO 2 with home CPAP and a vented mask, further confirming the need for high O 2 flow rates. In our clinical cohort, three patients required an O 2 flow rate above 80 L/min: this very high rate causes two concerns. Firstly, we did not know the lung compliance of these patients. Secondly, the O 2 flow rate required to achieve a given FiO 2 is likely to be underestimated with the experimental model compared to the clinical situation, since no gas exchange occurs with an artificial lung. For instance, in a patient, with a 21% FiO 2 , the partial pressure of O 2 in the inspired air will be 160 mm Hg, while in the expired air (at sea level) it will be 120 mm Hg due to oxygen absorption. Thus, in in vivo conditions even higher O 2 flows than those reported in this study may be required. 13 Another important point is that many teams use helmets to ventilate patients with Covid-19. 2, 14 Helmets could be more advantageous than oronasal masks because of the lower rate of unintentional leakage; this would allow lower oxygen flow rates to be used to achieve sufficient FiO 2 levels for patients with severe hypoxemia.

Studies have shown that patients who cannot be intubated require a high FiO 2 to maintain their SpO 2 above 92%, 3, 15 and that poor oxygenation is strongly associated with mortality. 3, 16 Our study provides valuable data to guide clinicians in the use of O 2 when using home CPAP in patients with severe Covid-19 who cannot be intubated. The results showed that these patients can be successfully treated with home CPAP devices, or NIV devices in CPAP mode, with vented masks, if a high O 2 flow rate is provided. However, close monitoring of unintentional leaks is crucial to ensure a sufficient FiO 2 for the treatment of severe hypoxemia in these patients.

All authors participated in the study design, research, and manuscript preparation. Dr. Marius Lebret is the guarantor of the content of the manuscript, including the data and analysis.

Funding was provided by Asten Santé.

ML reports receiving personal fees from Air Liquid Medical Systems and non-financial support from NOMICS over the past 3 years, for work unrelated to the work presented here. ML is a part-time employee of Air Liquide Medical System (Med2lab).

YC, CM and GP work as consultants for Air Liquid Medical System.

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Dr. Marius Lebret is the guarantor of the content of the manuscript, including the data and analysis.The authors would like to thank Asten Santé for providing funding the trial. The authors would also like to thank Johanna Robertson for English editing.