Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Software for CT-image Analysis to Assist the Choice of Mechanical-ventilation Settings in Acute Respiratory Distress Syndrome

International audienceAcute respiratory distress syndrome (ARDS) is a critical impairment of the lung function, which occurs - among others - in severe cases of patients with Covid-19. Its therapeutic management is based on mechanical ventilation, but this may aggravate the patient's condition if the settings are not adapted to the actual lung state. Computed tomography images allow for assessing the lung ventilation with fine spatial resolution, but their quantitative analysis is hampered by the contrast loss due to the disease. This article describes software developed to assist the clinicians in this analysis by implementing semi-automatic algorithms as well as interactive tools. The focus is the assessment of the cyclic hyperinflation, which may lead to ventilator-induced lung injury. For this purpose aerated parts of the lungs were segmented in twenty ARDS patients, half with Covid-19. The results were in very good agreement with manual segmentation performed by experts: 5:3% (5.1 ml) mean difference in measured cyclic hyperinflation

Pressure support and positive end-expiratory pressure versus T-piece during spontaneous breathing trial in difficult weaning from mechanical ventilation: study protocol for the SBT-ICU study

International audienceAbstract Background Spontaneous breathing trials are performed in critically ill intubated patients in order to assess readiness to be weaned from mechanical ventilation. In patients with difficult weaning (i.e. not extubated after their first SBT), performing SBT using pressure support with or without positive end-expiratory pressure or using T-piece is debated. As ventilatory support during SBT is greater on pressure support than on T-piece and as positive end-expiratory pressure can prevent weaning-induced pulmonary oedema, we hypothesized that their combination and large use of post-extubation non-invasive ventilation may shorten the time until successful extubation as compared with T-piece, without increasing the rate of reintubation. Methods SBT-ICU is a monocentric prospective open labelled, randomized controlled superiority trial comparing two mechanical ventilation weaning strategies; i.e. daily spontaneous breathing trials using pressure support with positive end-expiratory pressure or T-piece. The primary outcome will be time until successful extubation (defined by as extubation, without reintubation or death within the seven following days). Discussion This paper describes the protocol of the SBT-ICU trial. Enrolment of patients in the study is ongoing. Trial registration ClinicalTrials.gov NCT03861117. Registered on March 1, 2019, before the beginning of inclusion

Non-invasive quantification of acute macrophagic lung inflammation with [11C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome

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Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study

International audienceBackground Experimentally, ultra-protective ventilation (UPV, tidal volumes [V T ] &lt; 4 mL.kg −1 ) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS. Methods ARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (V T 1 mL.kg −1 , positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH 2 O and respiratory rate [RR] at 5 min −1 under VV-ECMO) or PV (V T 6 mL.kg −1 , PEEP set to obtain plateau pressure between 28 and 30 cmH 2 O and RR at 25 min −1 ) during 4 h. After 4 h, a positron emission tomography with [ 11 C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [ 11 C](R)-PK11195 lung uptake. [ 11 C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis. Results Five pigs were randomized to each study group. Arterial O 2 partial pressure to inspired O 2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68–80] mmHg in a PV group vs. 87 [69–133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [ 11 C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20–0.59] in UPV animals and 1.01 [IQR, 0.75–1.59] in PV animals, p = 0.01). Regional [ 11 C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance. Conclusion In an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of V T -derived determinants of VILI

Prone position decreases acute lung inflammation measured by [ 11 C](R)-PK11195 positron emission tomography in experimental acute respiratory distress syndrome

International audienceProne position decreases acute lung macrophage inflammation quantified in vivo with [ 11 C](R)-PK11195 positron emission tomography in an experimental acute respiratory distress syndrome. Regional macrophage inflammation is maximal in the most anterior and posterior lung section of supine animals, in relation with increased regional tidal strain and hyperinflation, and reduced regional lung compliance

Data_Sheet_1_Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study.docx

BackgroundExperimentally, ultra-protective ventilation (UPV, tidal volumes [VT] −1) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS.MethodsARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (VT 1 mL.kg−1, positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH2O and respiratory rate [RR] at 5 min−1 under VV-ECMO) or PV (VT 6 mL.kg−1, PEEP set to obtain plateau pressure between 28 and 30 cmH2O and RR at 25 min−1) during 4 h. After 4 h, a positron emission tomography with [11C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [11C](R)-PK11195 lung uptake. [11C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis.ResultsFive pigs were randomized to each study group. Arterial O2 partial pressure to inspired O2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68–80] mmHg in a PV group vs. 87 [69–133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [11C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20–0.59] in UPV animals and 1.01 [IQR, 0.75–1.59] in PV animals, p = 0.01). Regional [11C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance.ConclusionIn an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of VT-derived determinants of VILI.</p

Quantitative-analysis of computed tomography in COVID-19 and non COVID-19 ARDS patients: A case-control study

International audienceHighlights• Lung weight is significantly increased in all COVID+ ARDS patients.• Lung potential for recruitment of COVID+ ARDS patients is lower than COVID− ARDS.• A substantial proportion of COVID+ patients exhibit large amount of tidal hyperinflation.PurposeThe aim of this study was to assess whether the computed tomography (CT) features of COVID-19 (COVID+) ARDS differ from those of non-COVID-19 (COVID−) ARDS patients.Materials and methodsThe study is a single-center prospective observational study performed on adults with ARDS onset ≤72 h and a PaO2/FiO2 ≤ 200 mmHg. CT scans were acquired at PEEP set using a PEEP-FiO2 table with VT adjusted to 6 ml/kg predicted body weight.Results22 patients were included, of whom 13 presented with COVID-19 ARDS. Lung weight was significantly higher in COVID− patients, but all COVID+ patients presented supranormal lung weight values. Noninflated lung tissue was significantly higher in COVID− patients (36 ± 14% vs. 26 ± 15% of total lung weight at end-expiration, p < 0.01). Tidal recruitment was significantly higher in COVID− patients (20 ± 12 vs. 9 ± 11% of VT, p < 0.05). Lung density histograms of 5 COVID+ patients with high elastance (type H) were similar to those of COVID− patients, while those of the 8 COVID+ patients with normal elastance (type L) displayed higher aerated lung fraction

Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial

Abstract Background The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation. Methods The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH2O) and PEEP (5 cmH2O). In case of SBT success, an additional SBT with TP was performed. Failure of this SBT-TP was an additional criterion for post-extubation NIV in this group in addition to other recommended criteria. In the standard weaning group, SBT was performed with TP, and NIV was performed according to international guidelines. The primary outcome criterion was the time between inclusion and successful extubation evaluated with a Cox model with adjustment on randomization strata. Results From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58–73] vs. 62 [55–71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50–436] vs. 95 [47–232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55–1.42] using the standard weaning group as a reference; p = 0.60). All secondary outcomes were not significantly different between groups. Conclusion An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy. Trial registration The trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient. https://clinicaltrials.gov/study/NCT03861117

Precision of CT-derived alveolar recruitment assessed by human observers and a machine learning algorithm in moderate and severe ARDS

International audienceBACKGROUND: Assessing measurement error in alveolar recruitment on computed tomography (CT) is of paramount importance to select a reliable threshold identifying patients with high potential for alveolar recruitment and to rationalize positive end-expiratory pressure (PEEP) setting in acute respiratory distress syndrome (ARDS). The aim of this study was to assess both intra- and inter-observer smallest real difference (SRD) exceeding measurement error of recruitment using both human and machine learning-made lung segmentation (i.e., delineation) on CT. This single-center observational study was performed on adult ARDS patients. CT were acquired at end-expiration and end-inspiration at the PEEP level selected by clinicians, and at end-expiration at PEEP 5 and 15 cmH(2)O. Two human observers and a machine learning algorithm performed lung segmentation. Recruitment was computed as the weight change of the non-aerated compartment on CT between PEEP 5 and 15 cmH(2)O. RESULTS: Thirteen patients were included, of whom 11 (85%) presented a severe ARDS. Intra- and inter-observer measurements of recruitment were virtually unbiased, with 95% confidence intervals (CI(95%)) encompassing zero. The intra-observer SRD of recruitment amounted to 3.5 [CI(95%) 2.4-5.2]% of lung weight. The human-human inter-observer SRD of recruitment was slightly higher amounting to 5.7 [CI(95%) 4.0-8.0]% of lung weight, as was the human-machine SRD (5.9 [CI(95%) 4.3-7.8]% of lung weight). Regarding other CT measurements, both intra-observer and inter-observer SRD were close to zero for the CT-measurements focusing on aerated lung (end-expiratory lung volume, hyperinflation), and higher for the CT-measurements relying on accurate segmentation of the non-aerated lung (lung weight, tidal recruitment…). The average symmetric surface distance between lung segmentation masks was significatively lower in intra-observer comparisons (0.8 mm [interquartile range (IQR) 0.6-0.9]) as compared to human-human (1.0 mm [IQR 0.8-1.3] and human-machine inter-observer comparisons (1.1 mm [IQR 0.9-1.3]). CONCLUSIONS: The SRD exceeding intra-observer experimental error in the measurement of alveolar recruitment may be conservatively set to 5% (i.e., the upper value of the CI(95%)). Human-machine and human-human inter-observer measurement errors with CT are of similar magnitude, suggesting that machine learning segmentation algorithms are credible alternative to humans for quantifying alveolar recruitment on CT