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Background: To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2., Methods: This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021., Findings: ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference., Interpretation: Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres., Funding: None., Competing Interests: Declaration of interests MS reports lecture fees from Getinge, Drager, and Xenios, outside of the submitted work. AM-D reports grants from Addmedica, Baxter, Ferring, Fisher & Paykel, and Philips, and personal fees from Air Liquide, outside of the submitted work. PSc reports lecture fees from Getinge and scientific grants from the European Society of Intensive Medicine (ESICM) and the European Commission (Horizon 2020 Fast Track to Innovation; NCT04115709), and has co-organised an ARDS fellowship for the ESICM sponsored by Medtronic. BL reports fees from Abiomed, Getinge, Baxter, Novartis, Sanofi, Amomed, and Orion, outside of the submitted work. GG has received personal fees (payment for lectures) from Getinge, Draeger Medical, Biotest, GSK, Pfizer, Fisher & Paykel, and Cook Medical, and research grants from MSD and Fisher & Paykel. CG reports fees from Xenios, outside of the submitted work. JR reports lecture fees from Werfen and Gilead, and advisory fees from Medtronic, outside of the submitted work. AC reports grants from Getinge, and personal fees from Getinge, Baxter, and Xenios, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO., Methods: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group)., Results: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06)., Conclusions: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www., Clinicaltrials: gov ( NCT03918603 ). Registered 17 April 2019., (© 2022. The Author(s).)

Background: Although rarely addressed in the literature, a key question in the care of critically pregnant women with severe acute respiratory distress syndrome (ARDS), especially at the time of extracorporeal membrane oxygenation (ECMO) decision, is whether delivery might substantially improve the mother's and child's conditions. This multicenter, retrospective cohort aims to report maternal and fetal short- and long-term outcomes of pregnant women with ECMO-rescued severe ARDS according to the timing of the delivery decision taken before or after ECMO cannulation., Methods: We included critically ill women with ongoing pregnancy or within 15 days after a maternal/child-rescue-aimed delivery supported by ECMO for a severe ARDS between October 2009 and August 2021 in four ECMO centers. Clinical characteristics, critical care management, complications, and hospital discharge status for both mothers and children were collected. Long-term outcomes and premature birth complications were assessed., Results: Among 563 women on venovenous ECMO during the study period, 11 were cannulated during an ongoing pregnancy at a median (range) of 25 (21-29) gestational weeks, and 13 after an emergency delivery performed at 32 (17-39) weeks of gestation. Pre-ECMO PaO 2 /FiO 2 ratio was 57 (26-98) and did not differ between the two groups. Patients on ECMO after delivery reported more major bleeding (46 vs. 18%, p = 0.05) than those with ongoing pregnancy. Overall, the maternal hospital survival was 88%, which was not different between the two groups. Four (36%) of pregnant women had a spontaneous expulsion on ECMO, and fetal survival was higher when ECMO was set after delivery (92% vs. 55%, p = 0.03). Among newborns alive, no severe preterm morbidity or long-term sequelae were reported., Conclusion: Continuation of the pregnancy on ECMO support carries a significant risk of fetal death while improving prematurity-related morbidity in alive newborns with no difference in maternal outcomes. Decisions regarding timing, place, and mode of delivery should be taken and regularly (re)assess by a multidisciplinary team in experienced ECMO centers., (© 2022. The Author(s).)

Background: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies., Methods: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to "conventional" ECMO management (Supine group) in patients with severe ARDS., Results: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42-1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072)., Conclusions: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease., (© 2021 by The American Society of Hematology.)

Background: Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits. However, new studies have provided evidence contradicting these results., Method: A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48 h. An English language restriction was applied. Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model. Sensitivity and meta-regression analysis were performed., Results: From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO 2 /FIO 2 of 104 ± 35 mmHg. The cisatracurium group had the same risk of death at 28 days (RR, 0.90; 95% CI, 0.78-1.03; I 2  = 50%, p  = 0.12) and 90 days (RR, 0.81; 95% CI, 0.62-1.06; I 2  = 56%, p  = 0.06) as the control group (no cisatracurium). The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups. Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)-induced weakness. The PaO 2 /FIO 2 ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO 2 /FIO 2 ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity. Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes., Conclusion: NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness. However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Background: Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS). However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO). We tried to determine the frequency of Herpesviridae reactivation and its impact on patients' prognosis during ECMO for severe ARDS., Results: During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a veno-venous ECMO were included. Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone). HSV reactivation occurred earlier than CMV after the beginning of MV [(6-15) vs. 19 (13-29) days; p < 0.01] and after ECMO implementation [(2-8) vs. 14 (10-20) days; p < 0.01]. In univariate analysis, HSV/CMV reactivation was associated with a longer duration of mechanical ventilation [(22-52.5) vs. 17.5 (9-28) days; p < 0.01], a longer duration of ECMO [15 (10-22.5) vs. 9 (5-14) days; p < 0.01], and a prolonged ICU [29 (19.5-47.5) vs. 16 (9-30) days; p < 0.01] and hospital stay [44 (29-63.5) vs. 24 (11-43) days; p < 0.01] as compared to non-reactivated patients. However, in multivariate analysis, viral reactivation remained associated with prolonged MV only. When considered separately, both HSV and CMV reactivation were associated with a longer duration of MV as compared to non-reactivation patients [29 (19.5-41) and 28 (20.5-37), respectively, vs. 17.5 (9-28) days; p < 0.05]. Co-reactivation patients had a longer duration of MV [58.5 (38-72.3); p < 0.05] and ICU stay [51.5 (32.5-69) vs. 27.5 (17.75-35.5) and 29 (20-30.5), respectively] as compared to patients with HSV or CMV reactivation alone. In multivariate analysis, HSV reactivation remained independently associated with a longer duration of MV and hospital length of stay., Conclusions: Herpesviridae reactivation is frequent among patients with severe ARDS under veno-venous ECMO and is associated with a longer duration of mechanical ventilation. The direct causative link between HSV and CMV reactivation and respiratory function worsening under ECMO remains to be confirmed.

Background: The link between bacterial resistance and prognosis remains controversial. Predominant pathogen causing ventilator-associated pneumonia (VAP) is Pseudomonas aeruginosa (Pa), which has increasingly become multidrug resistant (MDR). The aim of this study was to evaluate the relationship between MDR VAP Pa episodes and 30-day mortality., Methods: From a longitudinal prospective French multicenter database (2010-2016), Pa VAP onset and physiological data were recorded. MDR was defined as non-susceptibility to at least 1 agent in 3 or more antimicrobial categories. To analyze if MDR episodes were associated with greater in-hospital 30-day mortality, we performed a multivariate survival analysis using the multivariate nonlinear frailty model., Results: A total of 230 patients presented 286 Pa VAP. A maximum of 3 episodes per patient was observed; 73 episodes were MDR and 213 were susceptible. In the multivariate model, factors independently associated with 30-day mortality included hospitalization in the 6 months preceding the first episode (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.50-3.60; P = .0002), chronic renal failure (HR, 2.34; 95% CI, 1.15-4.77; P = .0196), and Pa VAP recurrence (HR, 2.29; 95% CI, 1.79-4.87; P = .032). Finally, MDR Pa VAP was not associated with death (HR, 0.87; 95% CI; 0.52-1.45; P = .59)., Conclusions: This study did not identify a relationship between the resistance profile of Pseudomonas aeruginosa and mortality., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses., Methods: We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed., Results: Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate., Conclusions: The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.