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Objectives: Vascular complications after venoarterial extracorporeal membrane oxygenation (ECMO) remains poorly studied, although they may highly impact patient management after ECMO removal. Our aim was to assess their frequency, predictors, and management., Design: Retrospective, observational cohort study., Setting: Two ICUs from a tertiary referral academic hospital., Patients: Adult patients who were successfully weaned from venoarterial ECMO between January 2021 and January 2022., Interventions: None., Primary Outcome: Vascular complications frequency related to ECMO cannula., Measurements and Main Results: A total of 288 patients were implanted with venoarterial ECMO during the inclusion period. One hundred ninety-four patients were successfully weaned, and 109 underwent a CT examination to assess for vascular complications until 4 days after the weaning procedure. The median age of the cohort was 58 years (interquartile range [IQR], 46-64 yr), with a median duration of ECMO support of 7 days (IQR, 5-12 d). Vascular complications were observed in 88 patients (81%). The most frequent complication was thrombosis, either cannula-associated deep vein thrombosis (CaDVT) ( n = 63, 58%) or arterial thrombosis ( n = 36, 33%). Nonthrombotic arterial complications were observed in 48 patients (44%), with 35 (31%) presenting with bleeding. The most common site of CaDVT was the inferior vena cava, occurring in 33 (50%) of cases, with 20% of patients presenting with pulmonary embolism. There was no association between thrombotic complications and ECMO duration, anticoagulation level, or ECMO rotation flow. CT scans influenced management in 83% of patients. In-hospital mortality was 17% regardless of vascular complications., Conclusions: Vascular complications related to venoarterial ECMO cannula are common after ECMO implantation. CT allows early detection of complications after weaning and impacts patient management. Patients should be routinely screened for vascular complications by CT after decannulation., Competing Interests: Dr. Luyt received funding from Advanz Pharma and Merck; he received funding from Merck. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: The present study was designed to investigate the evolution and the impact of respiratory muscles function and limb muscles strength on weaning success in prolonged weaning of tracheotomized patients. The primary objective was to determine whether the change in respiratory muscles function and limb muscles strength over the time is or is not associated with weaning success., Methods: Tracheotomized patients who were ventilator dependent upon admission at a weaning center were eligible. Diaphragm function was assessed with the phrenic nerve stimulation technique and with ultrasound to measure the diaphragm thickening fraction (TFdi) and diaphragm excursion (EXdi). Global respiratory muscle function was assessed with the maximal inspiratory pressure (MIP) and the forced vital capacity (FVC). Limb muscle strength was measured with the Medical Research Council Score (MRC). Measurements were made on a weekly basis. Patients were compared according to their outcome at discharge: complete weaning, partial weaning or death., Results: Among the 60 patients who were enrolled, 30 patients finally achieved complete weaning, 20 had partial weaning and 10 died. At 6 months, 6 patients were lost of follow-up, 33 achieved complete weaning, 10 had partial weaning and 11 died. In median, 2 (1-9) assessments were performed per patient. Diaphragm dysfunction was present in all patients with a median Ptr,stim of 5.5 cmH 2 O (3.0-7.5). Ptr,stim, MIP, TFdi and EXdi at admission were not different between patients who achieved complete weaning and their counterparts. At discharge of the weaning center, MIP, Ptr,stim and EXdi significantly increased in patients who achieved complete weaning. The MRC score significantly increased only in patients with complete weaning. At discharge, diaphragm dysfunction was highly prevalent even in patients with complete weaning (Ptr,stim < 11 cmH 2 O in n = 11 (37%))., Conclusion: Respiratory muscle function and limb muscles strength are severely impaired in patients with prolonged weaning from mechanical ventilation. Significant improvement of diaphragm ultrasound indices was associated with successful weaning from mechanical ventilation and ICU-acquired weakness upon admission was significantly associated with good outcome suggesting that it was an amendable determinant of weaning failure in this population., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethics Committee of Sorbonne University approved the study (CER 2020-36). Oral information about the study was given to patients or relatives. Consent for publication: Not applicable. Competing interests: Martin Dres received fees from Lungpacer (expertise, lectures). A Demoule reports personal fees from Medtronic, grants, personal fees and non-financial support from Philips, personal fees from Baxter, personal fees from Hamilton, personal fees and non-financial support from Fisher & Paykel, grants from French Ministry of Health, personal fees from Getinge, grants and personal fees from Respinor, grants and non-financial support from Lungpacer, outside the submitted work. The other authors have no conflicts of interest to declare., (© 2024. The Author(s).)

Background: Monitoring fluid therapy is challenging in patients assisted with Veno-arterial ECMO. The aim of our study was to evaluate the usefulness of capillary refill time to assess the response to fluid challenge in patients assisted with VA-ECMO., Methods: Retrospective monocentric study in a cardiac surgery ICU. We assess fluid responsiveness after a fluid challenge in patients on VA-ECMO. We recorded capillary refill time before and after fluid challenge and the evolution of global hemodynamic parameters., Results: A total of 27 patients were included. The main indications for VA-ECMO were post-cardiotomy cardiogenic shock (44%). Thirteen patients (42%) were responders and 14 non-responders (58%). In the responder group, the index CRT decreased significantly (1.7 [1.5; 2.1] vs. 1.2 [1; 1.3] s; p = 0.01), whereas it remained stable in the non-responder group (1.4 [1.1; 2.5] vs. 1.6 [0.9; 1.9] s; p = 0.22). Diagnosis performance of CRT variation to assess response after fluid challenge shows an AUC of 0.68 (p = 0.10) with a sensitivity of 79% [95% CI, 52-92] and a specificity of 69% [95% CI, 42-87], with a threshold at 23%., Conclusion: In patients treated with VA-ECMO index capillary refill time is a reliable tool to assesses fluid responsiveness., Specialty: Critical care, Cardiac surgery, ECMO., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: This study aimed to identify perioperative risk factors of acute kidney injury after heart transplantation and to evaluate 1-year clinical outcomes., Design: A retrospective single-center cohort study., Setting: At a university hospital., Participants: All patients who underwent heart transplantation from January 2015 to December 2020., Interventions: None., Measurements and Main Results: The authors recorded acute kidney injury after heart transplantation. One-year mortality and renal function also were recorded. Risk factors of acute kidney injury were evaluated using a multivariate logistic regression model. Long-term survival was compared between patients developing acute kidney injury and those who did not, using a log-rank test. Among 209 patients included in this study, 134 patients (64% [95% CI (58; 71)]) developed posttransplantation acute kidney injury. Factors independently associated with acute kidney injury were high body mass index (odds ratio [OR]: 1.18 [1.02-1.38] per kg/m 2 ; p = 0.030), prolonged duration of cold ischemic period (OR: 1.11 [1.01-1.24] per 10 minutes; p = 0.039), and high dose of intraoperative dobutamine support (OR: 1.24 [1.06-1.46] per µg/kg/min; p = 0.008). At 1 year, patients who developed postoperative acute kidney injury had higher mortality rates (20% v 8%, p = 0.015). Among 172 survivors at 1 year, 82 survivors (48%) had worsened their renal function compared with preheart transplantation., Conclusions: This study highlighted the high incidence of acute kidney injury after heart transplantation and its impact on patient outcomes. Risk factors such as body mass index, prolonged cold ischemic period duration, and level of inotropic support with dobutamine were identified, providing insights for preventive strategies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery., Methods: In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat., Results: Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80)., Conclusion: Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: While numerous randomized controlled trials (RCTs) have been conducted in the field of trauma, a substantial portion of them are yielding negative results. One potential contributing factor to this trend could be the lack of agreement regarding the chosen definitions across different trials. The primary objective was to identify the terminology and definitions utilized for the characterization of multiple trauma patients within randomized controlled trials (RCTs)., Methods: A systematic review of the literature was performed in MEDLINE, EMBASE and clinicaltrials.gov between January 1, 2002, and July 31, 2022. RCTs or RTCs protocols were eligible if they included multiple trauma patients. The terms employed to characterize patient populations were identified, and the corresponding definitions for these terms were extracted. The subsequent impact on the population recruited was then documented to expose clinical heterogeneity., Results: Fifty RCTs were included, and 12 different terms identified. Among these terms, the most frequently used were "multiple trauma" (n = 21, 42%), "severe trauma" (n = 8, 16%), "major trauma" (n = 4, 8%), and trauma with hemorrhagic shock" (n = 4, 8%). Only 62% of RCTs (n = 31) provided a definition for the terms used, resulting a total of 21 different definitions. These definitions primarily relied on the injury severity score (ISS) (n = 15, 30%), displaying an important underlying heterogeneity. The choice of the terms had an impact on the study population, affecting both the ISS and in-hospital mortality. Eleven protocols were included, featuring five different terms, with "severe trauma" being the most frequent, occurring six times (55%)., Conclusion: This systematic review uncovers an important heterogeneity both in the terms and in the definitions employed to recruit trauma patients within RCTs. These findings underscore the imperative of promoting the use of a unique and consistent definition., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Postoperative pain management after orthotopic liver transplantation is complex due to impaired liver function and frequent acute kidney dysfunction. Subcostal transversus abdominis plane (TAP) block may be of interest in this population. The aim of this study was to evaluate the impact of subcostal TAP block on opioid consumption after liver transplantation., Methods: We conducted a before-and-after single center study. During the first period, we included patients whom did not receive an analgesic TAP block. During the second period, we included those with bilateral ultrasound-guided subcostal TAP block (20 mL ropivacaïne 0.2% each side). Patients requiring sedation within 48 hours of surgery as well as patients with combined liver and kidney transplants or skin-only closures were excluded. The primary outcome was cumulative oral morphine consumption within 48 hours after surgery. Secondary outcomes included pain scores and TAP block-related complications., Results: A total of 132 patients were included in the non-TAP block group and 78 patients in the TAP block group. The median oral morphine equivalent consumption (IQR) within 48 hours following surgery was 74 mg (39; 112) for the non-TAP block group and 50 mg (20; 80) for the TAP block group (p<0.001). There was no difference in pain scores between the two groups. No complications related to the TAP block were reported., Conclusion: Subcostal TAP block appears to have a small opioid reducing effect after orthotopic liver transplantation surgery., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Retrospective cohorts have suggested that levosimendan may facilitate the weaning of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We therefore studied this clinical question by emulating a randomized trial with observational data., Methods: All patients with refractory postcardiotomy cardiogenic shock and assisted with VA-ECMO, admitted to a surgical intensive care unit at La Pitié-Salpêtrière Hospital between 2016 and 2019, were eligible. To avoid immortal-time bias, we emulated a target trial sequentially comparing levosimendan administration versus no levosimendan administration in patients treated with VA-ECMO. The primary outcome was time to successful ECMO weaning. The secondary outcomes were 30-day and 1-year mortality. We performed a multivariable analysis to adjust for confounding at baseline., Results: Two hundred and thirty-nine patients were included in the study allowing building a nested trials cohort of 1434 copies of patients. No association of levosimendan treatment and VA-ECMO weaning was found (HR = 0.91, [0.57; 1.45], p = 0.659 in multivariable analysis), or 30-day mortality (OR = 1.03, [0.52; 2.03], p = 0.940) and 1-year mortality (OR = 1.00, [0.53; 1.89], p = 0.999)., Conclusions: Using the emulated target trial framework, this study did not find any association of levosimendan treatment and ECMO weaning success after postcardiotomy cardiogenic shock. However, the population of interest remains heterogeneous and subgroups might benefit from levosimendan., (© 2023. The Author(s).)

Background: Post-cardiotomy low cardiac output syndrome (PC-LCOS) is a life-threatening complication after cardiac surgery involving a cardiopulmonary bypass (CPB). Mechanical circulatory support with veno-arterial membrane oxygenation (VA-ECMO) may be necessary in the case of refractory shock. The objective of the study was to develop a machine-learning algorithm to predict the need for VA-ECMO implantation in patients with PC-LCOS., Patients and Methods: Patients were included in the study with moderate to severe PC-LCOS (defined by a vasoactive inotropic score (VIS) > 10 with clinical or biological markers of impaired organ perfusion or need for mechanical circulatory support after cardiac surgery) from two university hospitals in Paris, France. The Deep Super Learner, an ensemble machine learning algorithm, was trained to predict VA-ECMO implantation using features readily available at the end of a CPB. Feature importance was estimated using Shapley values., Results: Between January 2016 and December 2019, 285 patients were included in the development dataset and 190 patients in the external validation dataset. The primary outcome, the need for VA-ECMO implantation, occurred respectively, in 16% (n = 46) and 10% (n = 19) in the development and the external validation datasets. The Deep Super Learner algorithm achieved a 0.863 (0.793-0.928) ROC AUC to predict the primary outcome in the external validation dataset. The most important features were the first postoperative arterial lactate value, intraoperative VIS, the absence of angiotensin-converting enzyme treatment, body mass index, and EuroSCORE II., Conclusions: We developed an explainable ensemble machine learning algorithm that could help clinicians predict the risk of deterioration and the need for VA-ECMO implantation in moderate to severe PC-LCOS patients., (Copyright © 2022 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: The evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic., Aims: To develop and validate a score to predict outcomes in patients hospitalized with COVID-19., Methods: All consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort., Results: Among 2873 patients analysed (57.9% men; 66.6±17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n=2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75-0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores., Conclusions: The CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources., (Copyright © 2022. Published by Elsevier Masson SAS.)

Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1-4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016., (© 2022. The Author(s).)

Background: Although predictive models have already integrated demographic factors and comorbidities as risk factors for a prolonged hospital stay, factors related to anaesthesia management in ambulatory surgery have not been yet characterized. This study aims to identify anaesthetic factors associated with a prolonged discharge time in ambulatory surgery., Methods: All clinical records of patients who underwent ambulatory cholecystectomy in a French University Hospital (Hôpital Saint Antoine, Paris) between January 1st, 2012 and December 31st, 2018 were retrospectively reviewed. The primary endpoint was the discharge time, defined as the time between the end of surgery and discharge. A multivariable Cox proportional-hazards model was fitted to investigate the factors associated with a prolonged discharge time., Results: Five hundred and thirty-five (535) patients were included. The median time for discharge was 150 min (interquartile range - IQR [129-192]). A bivariable analysis highlighted a positive correlation between discharge timeline and the doses-weight of ketamine and sufentanil. In the multivariable Cox proportional hazards model analysis, the anaesthesia-related factors independently associated with prolonged discharge time were the dose-weight of ketamine in interaction with the dose weight of sufentanil (HR 0.10 per increment of 0.1 mg/kg of ketamine or 0.2 μg/kg of sufentanil, CI 95% [0.01-0.61], p = 0.013) and the non-use of a non-steroidal anti-inflammatory drug (NSAID) (HR 0.81 [0.67-0.98], p = 0.034). Twenty patients (4%) had unscheduled hospitalization following surgery., Conclusion: Anaesthesia management, namely the use of ketamine and the non-use of NSAID, affects time to hospital discharge., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Hospital-acquired pneumonia (HAP) is the most common and severe complication in patients treated with venoarterial extracorporeal membrane oxygenation (VA ECMO) and its diagnosis remains challenging. Nothing is known about the usefulness of lung ultrasound (LUS) in early detection of HAP in patients treated with VA ECMO. Also, LUS and chest radiography were performed when HAP was suspected in cardiac critically ill adult VA ECMO presenting with acute respiratory failure. The sonographic features of HAP in VA ECMO patients were determined and we assessed the performance of the lung ultrasound simplified clinical pulmonary score (LUS-sCPIS), the sCPIS and bioclinical parameters or chest radiography alone for early diagnosis of HAP., Results: We included 70 patients, of which 44 (63%) were independently diagnosed with HAP. LUS examination revealed that color Doppler intrapulmonary flow (P = 0.0000043) and dynamic air bronchogram (P = 0.00024) were the most frequent HAP-related signs. The LUS-sCPIS (area under the curve = 0.77) yielded significantly better results than the sCPIS (area under the curve = 0.65; P = 0.004), while leukocyte count, temperature and chest radiography were not discriminating for HAP diagnosis., Discussion: Diagnosis of HAP is a daily challenge for the clinician managing patients on venoarterial ECMO. Lung ultrasound can be a valuable tool as the initial imaging modality for the diagnosis of pneumonia. Color Doppler intrapulmonary flow and dynamic air bronchogram appear to be particularly insightful for the diagnosis of HAP., (© 2022. The Author(s).)

Aims: Although cardiac involvement has prognostic significance in coronavirus disease 2019 (COVID-19) and is associated with severe forms, few studies have explored the prognostic role of transthoracic echocardiography (TTE). We investigated the link between TTE parameters and prognosis in COVID-19., Methods and Results: Consecutive patients with COVID-19 admitted to 24 French hospitals were retrospectively included. Comprehensive data, including clinical and biological parameters, were recorded at admission. Focused TTE was performed during hospitalization, according to clinical indication. Patients were followed for a primary composite outcome of death or transfer to intensive care unit (ICU) during hospitalization. Among 2878 patients, 445 (15%) underwent TTE. Most of these had cardiovascular risk factors, a history of cardiovascular disease, and were on cardiovascular treatments. Dilatation and dysfunction were observed in, respectively, 12% (48/412) and 23% (102/442) of patients for the left ventricle, and in 12% (47/407) and 16% (65/402) for the right ventricle (RV). Primary composite outcome occurred in 44% (n = 196) of patients [9% (n = 42) for death without ICU transfer and 35% (n = 154) for admission to ICU]. RV dilatation was the only TTE parameter associated with the primary outcome. After adjustment, male sex [hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.09 - 2.25; P = 0.02], higher body mass index (HR 1.10, 95% CI 1.02 - 1.18; P = 0.01), anticoagulation (HR 0.53, 95% CI 0.33 - 0.86; P = 0.01), and RV dilatation (HR 1.66, 95% CI 1.05 - 2.64; P = 0.03) remained independently associated with the primary outcome., Conclusion: Echocardiographic evaluation of RV dilatation could be useful for assessing risk of severe COVID-19 developing in hospitalized patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Although 18-45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18-45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18-45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18-45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18-45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population.

Background: Our study aimed to compare the clinical outcomes of patients with and without diabetes admitted to hospital with COVID-19., Methods: This retrospective multicentre cohort study comprised 24 tertiary medical centres in France, and included 2851 patients (675 with diabetes) hospitalized for COVID-19 between 26 February and 20 April 2020. A propensity score-matching (PSM) method (1:1 matching including patients' characteristics, medical history, vital statistics and laboratory results) was used to compare patients with and without diabetes (n = 603 per group). The primary outcome was admission to an intensive care unit (ICU) and/or in-hospital death., Results: After PSM, all baseline characteristics were well balanced between those with and without diabetes: mean age was 71.2 years; 61.8% were male; and mean BMI was 29 kg/m 2 . A history of cardiovascular, chronic kidney and chronic obstructive pulmonary diseases were found in 32.8%, 22.1% and 6.4% of participants, respectively. The risk of experiencing the primary outcome was similar in patients with or without diabetes [hazard ratio (HR): 1.16, 95% confidence interval (CI): 0.95-1.41; P = 0.14], and was 1.29 (95% CI: 0.97-1.69) for in-hospital death, 1.26 (95% CI: 0.9-1.72) for death with no transfer to an ICU and 1.14 (95% CI: 0.88-1.47) with transfer to an ICU., Conclusion: In this retrospective study cohort of patients hospitalized for COVID-19, diabetes was not significantly associated with a higher risk of severe outcomes after PSM., Trial Registration Number: NCT04344327., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis. Only limited data are available on the characteristics and outcomes of patients hospitalized for COVID-19 in France., Aims: To investigate the characteristics, cardiovascular complications and outcomes of patients hospitalized for COVID-19 in France., Methods: The Critical COVID-19 France (CCF) study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection hospitalized in 24 centres between 26 February and 20 April 2020. Patients admitted directly to intensive care were excluded. Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death., Results: Of 2878 patients included (mean±SD age 66.6±17.0 years, 57.8% men), 360 (12.5%) died in the hospital setting, of which 7 (20.7%) were transferred to intensive care before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P<0.001), male sex (HR 1.69, 95% CI 1.11-2.57; P=0.01), diabetes (HR 1.72, 95% CI 1.12-2.63; P=0.01), chronic kidney failure (HR 1.57, 95% CI 1.02-2.41; P=0.04), elevated troponin (HR 1.66, 95% CI 1.11-2.49; P=0.01), elevated B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide (HR 1.69, 95% CI 1.0004-2.86; P=0.049) and quick Sequential Organ Failure Assessment score ≥2 (HR 1.71, 95% CI 1.12-2.60; P=0.01) were independently associated with in-hospital death., Conclusions: In this large nationwide cohort of patients hospitalized for COVID-19 in France, cardiovascular comorbidities and risk factors were associated with a substantial morbi-mortality burden., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimer, and increased frequency of venous thromboembolism., Aim: To explore the association between D-dimer at admission and in-hospital mortality in patients hospitalised for COVID-19, with or without symptomatic venous thromboembolism., Methods: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality and venous thromboembolism) of patients hospitalised for COVID-19 in medical wards were retrospectively analysed in a multicenter study in 24 French hospitals., Results: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration>1128ng/mL as the best cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 60-69), with a sensitivity of 71.1% (95% CI 62-78) and a specificity of 55.6% (95% CI 52-58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalisation. Among 545 (47.2%) patients with D-dimer concentration>1128ng/mL at admission, 86 (15.8%) deaths occurred during hospitalisation. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration>1128ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05-4.69; P<0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31-3.4; P<0.01)., Conclusions: D-dimer concentration>1128ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalised for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalisation., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population., Aims: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19., Methods: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death., Results: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure., Conclusions: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited., Aims: To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction., Methods: We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation., Results: Overall, 2809 patients (mean age 66.4±16.9years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score>1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06-1.90; P=0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13-2.27; P=0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79-1.81; P=0.41)., Conclusions: History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.

Objective: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) commonly is used to manage refractory cardiogenic shock after cardiac surgery, with 31% to 76% of patients successfully weaned off their ECMO. However, it is associated with high mortality rates, and 20% to 65% of weaned patients do not survive to hospital discharge. This study aimed to assess the incidence of ECMO weaning-related shock, the risk factors, and prognosis in the intensive care unit (ICU)., Design: Retrospective observational cohort study., Setting: Surgical ICU of Cardiology Institute of Pitié-Salpêtrière University Hospital (Paris-France)., Participants: Patients who were assisted with a peripheral VA-ECMO from January 2015 to December 2017 were included. Patients with venovenous, central, or right ECMO were excluded., Measurements: The authors collected data on patients' characteristics, during and after surgery. The indications for VA-ECMO implantation were ventricular dysfunction, primary graft dysfunction, and refractory cardiac arrest. Weaning-related shock was defined as the need to introduce or increase the dose of catecholamine at ECMO explantation or in the following week., Results: After weaning off VA-ECMO, 56 of 146 patients (38.4%) presented weaning-related shock: 55% were septic shocks, 12.5 % were caused by right ventricle failure, and 7.1% by hemorrhage. ICU mortality was 42% versus 8% in patients who did not present shock. Multivariate analysis showed that patients with pulmonary hypertension and those with norepinephrine before weaning were more likely to develop shock., Conclusion: ECMO weaning-related shock is frequent in patients with refractory cardiogenic shock after cardiac surgery. This is most commonly caused by sepsis and causes higher mortality rates, calling for further evaluation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Postcardiotomy cardiogenic shock occurs in 2-6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients., Design: Retrospective observational cohort study between January 2013 and December 2016., Setting: An 18-bed surgical ICU in a university hospital., Patients: A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients., Interventions: None., Measurements and Main Results: The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3-16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31-6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01-1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02-1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001-1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006-1.018]; p < 0.001) on the day of implantation., Conclusions: Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients., Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7., Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7., Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Aims: While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse. We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients., Methods and Results: In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19. Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded. Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA. The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001). In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively]. In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002)., Conclusion: PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

When used as an add-on to regional anesthesia, virtual reality (VR) has been reported to provide anxiety-reducing benefits and sedation-sparing effects. However, its impact on patient satisfaction is still a matter of controversy. We investigated the feasibility and benefits of implementing intraoperative VR distraction in a French University Hospital (Hôpital Saint-Antoine, AP-HP). This monocentric observational before-after study included 100 patients who underwent ambulatory upper limb surgery under peripheral nerve block in January 2019, 50 before and 50 after implementation of an intraoperative VR distraction protocol. Primary outcome was patient self-rated satisfaction score evaluated right after surgery. Secondary outcomes included 2-month patient-reported satisfaction score, perioperative self-rated anxiety and intraoperative hemodynamic changes. Compared to former standard care, VR distraction was associated with significantly higher postoperative satisfaction scores (10 [IQR 9; 10] vs. 9 [8; 10], p < 0.001) still reported two months after surgery (10 [10;10] vs. 10 [8.5;10], p = 0.06). Patient median intraoperative anxiety score was lower in the VR group, compared to Standard Care group (0 [0; 2] vs. 3 [0.25; 7], p < 0.001), and occurrence of intraoperative hemodynamic changes was also lessened in the VR group (2% vs. 16%, 0R = 0.11[95% CI 0.002-0.87], p = 0.031). The present findings suggest that VR distraction program in the operating room could effectively improve patient satisfaction with anxiety-reduction and hemodynamic benefits.

Objectives: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease., Design: A multicentric retrospective cohort study between January 2010 and August 2017., Setting: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network., Patients: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded., Interventions: None., Measurement and Main Results: We included 134 patients (median Sequential Organ Failure Assessment 10 [8-12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9-22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32-7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21-3.31; p = 0.016) were independently associated with invasive fungal disease., Conclusions: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.

Background: Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB., Methods: This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB. TPVB was performed before surgery under ultrasound guidance with 20 mL of 0.75% ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the anterior chest wall. The PDR was defined as the maximal increase in pupil diameter after a standardized noxious stimulus, expressed as a percentage of the initial pupil diameter. The PDR was recorded twice in the same eye for each patient after a stimulus on both the TPVB and the control sides. Postoperative pain scores were recorded in a postanesthesia care unit. The primary outcome was the difference between the PDR on the TPVB and the control sides., Results: The median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%-66%) on the control side. There was a significant difference in the PDR between the TPVB and the control sides with a Hodges-Lehmann estimate of absolute difference of 37% points (95% confidence interval, 25-52, P < .001). Median postoperative pain scores (interquartile range) in the postanesthesia care unit were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a linear correlation between maximal postoperative pain scores and the PDR on the TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence interval, 0.06-0.66, P = .02). No correlation was found between the number of blocked dermatomes and maximal postoperative pain scores (P = .06) or between the number of blocked dermatomes and the PDR on the TPVB side (P = .15)., Conclusions: This proof-of-concept trial suggests that the effect of TPVB could be monitored by measuring the PDR after anterior chest wall stimulation in the dermatome of interest.