Publications by authors named "Laurent Argaud"

213 Publications

Assessment of open-source, intermediate and ICU ventilators to face the COVID-19 pandemic: A bench study.

Eur J Anaesthesiol 2022 Jan 3. Epub 2022 Jan 3.

From the Médecine Intensive-Réanimation, Hôpital Edouard Herriot, University Hospital Lyon (CG, MC, FD, FC, LA), Institut Mondor de Recherches Biomédicales, INSERM 955, CNRS ERL 7000 (BL), Faculté de Santé (3ème étage, porte 3026), Créteil (BL) and Médecine Intensive-Réanimation, CHU Grenoble Alpes CS 10217, Grenoble Cedex 9, France (NT).

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http://dx.doi.org/10.1097/EJA.0000000000001657DOI Listing
January 2022

Response.

Chest 2021 12;160(6):e678

Médecine Intensive-Réanimation, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France; Université de Lyon, INSERM UMR1060 (CarMeN), Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2021.07.048DOI Listing
December 2021

Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study.

Mycoses 2022 Feb 8;65(2):226-232. Epub 2021 Dec 8.

AP-HP, Hôpital Saint-Louis, Medical ICU, Université de Paris, Paris, France.

Objectives: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality.

Methods: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts.

Results: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality.

Conclusions: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.
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http://dx.doi.org/10.1111/myc.13407DOI Listing
February 2022

Nationwide retrospective study of critically ill adults with sickle cell disease in France.

Sci Rep 2021 11 30;11(1):23132. Epub 2021 Nov 30.

Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Hôtel-Dieu, 30 Bd. Jean Monnet, 44093, Nantes Cedex 1, France.

Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.
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http://dx.doi.org/10.1038/s41598-021-02437-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632921PMC
November 2021

Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study.

Lancet Respir Med 2021 Nov 26. Epub 2021 Nov 26.

CHU Necker Enfants Malades-APHP, Paris, France.

Background: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care.

Methods: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221.

Findings: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001).

Interpretation: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19.

Funding: Pfizer.
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http://dx.doi.org/10.1016/S2213-2600(21)00442-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626095PMC
November 2021

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

PLoS One 2021 24;16(11):e0260656. Epub 2021 Nov 24.

Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260656PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612507PMC
December 2021

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

Lancet Respir Med 2021 Nov 11. Epub 2021 Nov 11.

Service de Réanimation Polyvalente, Centre Hospitalier Intercommunal de Poissy Saint Germain en Laye, Poissy, France; Service de Médecine Intensive et Réanimation, Centre Hospitalier De Tarbes, Tarbes, France.

Background: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury.

Methods: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580.

Findings: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089).

Interpretation: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials.

Funding: Programme Hospitalier de Recherche Clinique.
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http://dx.doi.org/10.1016/S2213-2600(21)00440-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585489PMC
November 2021

Electrocardiogram monitoring in the prone position in coronavirus disease 2019 acute respiratory distress syndrome.

Eur J Cardiovasc Nurs 2021 11;20(8):792-796

Service de Médecine Intensive - Réanimation, Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive - Réanimation, 5, place d'Arsonval, Lyon F-69437, France.

Aims: Prone positioning is increasingly used for treating coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). In these high-risk patients for cardiovascular events who may spend more than 16 h a day in the prone position, an adequate monitoring of electrocardiogram (ECG) is mandatory. However, effects of prone positioning on the ECG are unknown as is the validity of the ECG recorded with electrodes placed dorsally. We aimed to compare ECG data obtained in the prone position from five electrodes positioned conventionally and dorsally, and to assess the effects of the change of position (from supine to prone) on the ECGs in patients with COVID-19 ARDS.

Methods And Results: In patients with COVID-19 ARDS for whom the prone position was indicated, seven-lead ECG (frontal plane leads and V6) performed in the supine and the prone position with electrodes positioned conventionally and dorsally were compared. A total of 22 patients [20 (91%) males] were included. Among them, 10 (45%) patients had structural or ischaemic heart disease. After prone positioning, PR duration significantly increased and QRS duration significantly decreased whereas QT interval did not significantly change. In the prone position, there were excellent correlations between QRS axis, PR, RR, QRS, and QT intervals durations measured with electrodes placed on the torso and dorsally (with no change in the position of V6).

Conclusion: Prone positioning induced significant change in the ECG. In the prone position, ECG can be reliably monitored with four electrodes translated from conventional position to the back and with a precordial electrode left in V6 position.
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http://dx.doi.org/10.1093/eurjcn/zvab094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574317PMC
November 2021

Effects of dexamethasone on immune dysfunction and ventilator-associated pneumonia in COVID-19 acute respiratory distress syndrome: an observational study.

J Intensive Care 2021 Oct 18;9(1):64. Epub 2021 Oct 18.

Faculté de médecine Lyon-Est, Université de Lyon, Université Claude Bernard Lyon 1, F-69437, Lyon, France.

Dexamethasone improves survival of patients with COVID-19 acute respiratory distress syndrome, but might shorten the delay between the start of invasive mechanical ventilation and the occurrence of ventilator-associated pneumonia, suggesting possible worsening of COVID-19-induced immune dysfunction with this treatment. In a prospective observational study, we found that mechanically ventilated patients with COVID-19 treated with dexamethasone presented earlier ventilator-associated pneumonia, had significantly lower monocyte Human Leukocyte Antigen-DR expression and number of circulating CD4 + cells after ICU admission, than those not treated with corticoids.
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http://dx.doi.org/10.1186/s40560-021-00580-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522132PMC
October 2021

Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial.

Trials 2021 Oct 11;22(1):692. Epub 2021 Oct 11.

Université Lyon 1, Université de Lyon, Lyon, France.

Background: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation.

Methods: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO/FiO ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles.

Discussion: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing.

Trial Registration: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.
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http://dx.doi.org/10.1186/s13063-021-05665-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503716PMC
October 2021

Prone Position in Coronavirus Disease 2019 and Noncoronavirus Disease 2019 Acute Respiratory Distress Syndrome: An International Multicenter Observational Comparative Study.

Crit Care Med 2021 Sep 24. Epub 2021 Sep 24.

Department of Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, United Kingdom. Centre of Human Applied Physiological Sciences, King's College London, London, United Kingdom. Department of Anesthesiology and Intensive Care, ASST Santi e Paolo Hospital, University of Milan, Milan, Italy. University of Grenoble-Alpes, Grenoble, France. Médecine Intensive-Réanimation, Hôpital Edouard Herriot 5, Lyon, France. Service d'Anesthésie-Réanimation, Hôpital Edouard Herriot 5, Lyon, France. Service d'Anesthésie-Réanimation, Médecine Intensive Groupement Hospitalier Lyon, Pierre Bénite, France. Service de Réanimation polyvalente, Centre Hospitalier Général, Roanne, France.

Objectives: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival.

Design: Retrospective, observational, multicenter, international cohort study.

Setting: Seven ICUs in Italy, United Kingdom, and France.

Patients: Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome).

Intervention: None.

Measurements And Main Results: Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse PaO2/FIO2 (13.0 kPa [interquartile range, 10.5-15.5 kPa] vs 14.1 kPa [interquartile range, 10.5-18.6 kPa]; p = 0.017) but greater compliance (38 mL/cm H2O [interquartile range, 27-53 mL/cm H2O] vs 31 mL/cm H2O [interquartile range, 21-37 mL/cm H2O]; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d [interquartile range, 0.7-5.0 d] vs 1.0 d [interquartile range, 0.5-2.9 d]; p = 0.03).The proportion of responders, defined by an increase in PaO2/FIO2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d [interquartile range, 0.7-4.2 d] vs 2.5 d [interquartile range, 0.8-6.2 d]; p = 0.06)]. Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa [interquartile range, 4-21 kPa] vs 7 kPa [interquartile range, 2-13 kPa]; p = 0.002).The variables independently associated with the "responder" category were PaO2/FIO2 preproning (odds ratio, 0.89 kPa-1 [95% CI, 0.85-0.93 kPa-1]; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 [95% CI, 0.89-0.99 d-1]; p = 0.019).The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 [95% CI, 1.01-1.05 yr-1]; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 [95% CI, 1.002-1.084 d-1]; p = 0.047); and change in PaO2/FIO2 on proning (odds ratio, 0.97 kPa-1 [95% CI, 0.95-0.99 kPa-1]; p = 0.002).

Conclusions: Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.
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http://dx.doi.org/10.1097/CCM.0000000000005354DOI Listing
September 2021

Seroconversion in septic ICU patients presenting with COVID-19: necessary but not sufficient.

Arch Med Res 2021 11 6;52(8):850-857. Epub 2021 Sep 6.

Pathophysiology of Injury-Induced Immunosuppression, Université Claude Bernard Lyon 1-Hospices Civils de Lyon-bioMérieux/Joint Research Unit HCL-bioMérieux, Edouard Herriot Hospital, Lyon, France; Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, Lyon, France. Electronic address:

Background: As COVID-19 pandemic and vaccination effects progress, research now focuses on adaptive immunological response to SARS-CoV-2. Few studies specifically investigated intensive care unit (ICU) patients, and little is known about kinetics of humoral response in such critically ill patients. In this context, the main objective of the present work was to perform a longitudinal analysis of the humoral response in critically ill COVID-19 patients with prolonged ICU stays in regard with initial inflammatory response, disease severity and mortality.

Methods: Over a 3 week period, circulating immunoglobulins (Ig) against SARS-CoV-2 along with several immunological and clinical parameters were measured in 64 ICU COVID-19 patients.

Results: Critically ill COVID-19 patients mounted a dynamic and sustained antibody response of both IgM and IgG as soon as the first day of ICU hospitalization. This serological response was not associated with any of the classical immunological parameters measured at ICU admission or with initial severity clinical scores. IgM and IgG levels and seroconversion trajectories were not associated with unfavourable outcome.

Conclusion: Despite rapid seroconversion and elevated humoral response, COVID-19 patients are still characterized by elevated mortality. Additional studies, including cytotoxic T cell functions, are mandatory to understand the immunological mechanisms contributing to long stay of COVID-19 patients in ICU.
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http://dx.doi.org/10.1016/j.arcmed.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418908PMC
November 2021

Short- and long-term prognosis of acute critically ill patients with systemic rheumatic diseases: A retrospective multicentre study.

Medicine (Baltimore) 2021 Sep;100(35):e26164

Université de Lyon, France.

Abstract: Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjögren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.
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http://dx.doi.org/10.1097/MD.0000000000026164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415942PMC
September 2021

Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study.

Crit Care Med 2022 Jan;50(1):e71-e79

Université de Lyon, INSERM UMR1060 (CarMeN), IRIS, Lyon, France.

Objectives: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure.

Design: Randomized blinded study (animal model).

Setting: University animal research facility.

Subjects: Twenty-four adult male "New Zealand White" rabbits.

Interventions: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period.

Measurements And Main Results: Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis.

Conclusions: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.
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http://dx.doi.org/10.1097/CCM.0000000000005233DOI Listing
January 2022

Combined use of a broad-panel respiratory multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP): a multicentre, parallel-group, open-label, individual randomised trial conducted in French intensive care units.

BMJ Open 2021 08 18;11(8):e048187. Epub 2021 Aug 18.

Service de Réanimation Infectieuse, Hôpital Bichat, Assistance Publique-Hopitaux de Paris, Paris, Île-de-France, France.

Introduction: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care.

Methods And Analysis: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period.

Ethics And Dissemination: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses.

Trial Registration Number: NCT03452826; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-048187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375718PMC
August 2021

Clinical and biological clusters of sepsis patients using hierarchical clustering.

PLoS One 2021 4;16(8):e0252793. Epub 2021 Aug 4.

UMR 1137 IAME INSERM- Paris Diderot University, Paris, France.

Background: Heterogeneity in sepsis expression is multidimensional, including highly disparate data such as the underlying disorders, infection source, causative micro-organismsand organ failures. The aim of the study is to identify clusters of patients based on clinical and biological characteristic available at patients' admission.

Methods: All patients included in a national prospective multicenter ICU cohort OUTCOMEREA and admitted for sepsis or septic shock (Sepsis 3.0 definition) were retrospectively analyzed. A hierarchical clustering was performed in a training set of patients to build clusters based on a comprehensive set of clinical and biological characteristics available at ICU admission. Clusters were described, and the 28-day, 90-day, and one-year mortality were compared with log-rank rates. Risks of mortality were also compared after adjustment on SOFA score and year of ICU admission.

Results: Of the 6,046 patients with sepsis in the cohort, 4,050 (67%) were randomly allocated to the training set. Six distinct clusters were identified: young patients without any comorbidities, admitted in ICU for community-acquired pneumonia (n = 1,603 (40%)); young patients without any comorbidities, admitted in ICU for meningitis or encephalitis (n = 149 (4%)); elderly patients with COPD, admitted in ICU for bronchial infection with few organ failures (n = 243 (6%)); elderly patients, with several comorbidities and organ failures (n = 1,094 (27%)); patients admitted after surgery, with a nosocomial infection (n = 623 (15%)); young patients with immunosuppressive conditions (e.g., AIDS, chronic steroid therapy or hematological malignancy) (n = 338 (8%)). Clusters differed significantly in early or late mortality (p < .001), even after adjustment on severity of organ dysfunctions (SOFA) and year of ICU admission.

Conclusions: Clinical and biological features commonly available at ICU admission of patients with sepsis or septic shock enabled to set up six clusters of patients, with very distinct outcomes. Considering these clusters may improve the care management and the homogeneity of patients in future studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336799PMC
November 2021

Assessment of Magnetic Resonance Imaging Changes and Functional Outcomes Among Adults With Severe Herpes Simplex Encephalitis.

JAMA Netw Open 2021 07 1;4(7):e2114328. Epub 2021 Jul 1.

Critical Care Unit, University Hospital of Rangueil, Toulouse, France.

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting.

Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission.

Design, Setting, And Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020.

Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission.

Main Outcomes And Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale.

Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions).

Conclusions And Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.14328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317014PMC
July 2021

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

Int J Environ Res Public Health 2021 07 15;18(14). Epub 2021 Jul 15.

Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France.

Introduction: can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. , the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for testing are obtained on admission, every 3-5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l'Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.
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http://dx.doi.org/10.3390/ijerph18147528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307155PMC
July 2021

Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial.

Ann Intensive Care 2021 Jul 22;11(1):114. Epub 2021 Jul 22.

Médecine Intensive Réanimation, CHU de Poitiers, Poitiers, France.

Background: Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity.

Methods: Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO/FiO < 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure.

Results: Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI - 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77-93] with noninvasive ventilation and 86% [78-92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission.

Conclusions: Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov ).
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http://dx.doi.org/10.1186/s13613-021-00892-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295638PMC
July 2021

Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol.

BMJ Open 2021 07 6;11(7):e044449. Epub 2021 Jul 6.

Intensive Care Unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.

Introduction: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission.

Methods And Analysis: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes.

Ethics And Dissemination: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals.

Trial Registration Number: NCT04422340.
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http://dx.doi.org/10.1136/bmjopen-2020-044449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264162PMC
July 2021

Differential effects of prone position in COVID-19-related ARDS in low and high recruiters.

Intensive Care Med 2021 09 28;47(9):1044-1046. Epub 2021 Jun 28.

Service de Médecine Intensive-Réanimation, Hospices Civils de Lyon, Hôpital Edouard Herriot, 5, place d'Arsonval, Cedex 03, 69437, Lyon, France.

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http://dx.doi.org/10.1007/s00134-021-06466-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236780PMC
September 2021

Bicentric evaluation of stabilizing sampling tubes for assessment of monocyte HLA-DR expression in clinical samples.

Cytometry B Clin Cytom 2021 Jun 12. Epub 2021 Jun 12.

Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, Lyon, France.

Background: Diminished expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR), measured by standardized flow cytometry procedure, is a reliable indicator of immunosuppression in severely injured intensive care unit patients. As such, it is used as stratification criteria in clinical trials evaluating novel immunostimulating therapies. Preanalytical constraints relative to the short delay between blood sampling and flow cytometry staining have nevertheless limited its use in multicentric studies. The objective of the present work was to compare mHLA-DR expression between whole blood samples simultaneously drawn in EDTA or Cyto-Chex BCT tubes.

Methods: In two university hospitals, mHLA-DR was assessed in fresh whole blood from septic patients (n = 12) and healthy donors (n = 6) simultaneously sampled on EDTA and Cyto-Chex BCT tubes. Staining was performed immediately after sampling and after blood storage at room temperature.

Results: We confirmed that samples collected in Cyto-Chex tube had substantially enhanced stability for mHLA-DR results (48-72 h) over those collected in EDTA. On baseline values, despite good correlation between tubes (r = 0.98, p < 0.001), mHLA-DR expression was systematically lower with Cyto-Chex BCT.

Conclusion: The present reports confirms the potential of Cyto-Chex BCT tubes to stabilize mHLA-DR expression before staining and extends the work of Quadrini et al. [Cytometry B 2021;100:103-114]. In centers without rapid access to flow cytometry facilities, it enables to tolerate delays in mHLA-DR staining. However, a 30% gap exists between results obtained with EDTA and Cyto-Chex BCT tubes. As current thresholds for clinical decisions were obtained with EDTA samples, further studies are needed to confirm clinical thresholds with Cyto-Chex BCT tubes.
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http://dx.doi.org/10.1002/cyto.b.22025DOI Listing
June 2021

Prediction of Brain Death After Out-of-Hospital Cardiac Arrest: Development and Validation of the Brain Death After Cardiac Arrest Score.

Chest 2021 07 8;160(1):139-147. Epub 2021 Jun 8.

Médecine Intensive-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; INSERM UMR1060 (CarMeN), Université de Lyon, Lyon, France. Electronic address:

Background: Among patients successfully resuscitated after an out-of-hospital cardiac arrest (OHCA), 10% to 15% evolve toward brain death (BD), thus becoming potential organ donors.

Research Question: Is it possible to establish a score for early estimation of BD risk after OHCA?

Study Design And Methods: The BD after cardiac arrest (BDCA) score was developed from data available within 24 hours after OHCA from two OHCA trials: Cyclosporine in Cardiac Arrest Resuscitation and Erythropoietin After OHCA. The BDCA score was then validated in another large prospective multicenter data set. The main outcome was the occurrence of BD. Independent prognostic covariates for BD were identified using a binomial two-stage adaptive least absolute shrinkage and selection operator procedure.

Results: The development cohort included 569 patients alive 24 hours after OHCA, among whom 84 (14.8%) experienced BD. Independent predictors of BD used to build the BDCA score were being female (4 points), nonshockable rhythm (24 points), cardiac cause of OHCA (-6 points), neurological cause of OHCA (45 points), natremia at 24 hours (natremia in millimoles per liter minus 140 points), and vasoactive drug at admission (4 points) and at 24 hours (6 points). The area under the curve (AUC) of the BDCA score was 0.82 (95% CI, 0.77-0.86), and the discrimination value in the validation cohort (n = 487) was consistent (AUC, 0.81; 95% CI, 0.76-0.86). In the validation cohort, BD occurred in 4.0%, 20.4%, and 67.7% of patients with scores of < 20, 20 to 50, and > 50, respectively.

Interpretation: The BDCA score allows early detection of patients with a high probability of experiencing BD, which may help increase organ donation after OHCA.

Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01595958, and ClinicalTrials.gov; No.: NCT00999583; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.01.056DOI Listing
July 2021

Lung ultrasound score as a tool to monitor disease progression and detect ventilator-associated pneumonia during COVID-19-associated ARDS.

Heart Lung 2021 Sep-Oct;50(5):700-705. Epub 2021 May 31.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, F-69437, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, Faculté de médecine Lyon-Est, F-69373, Lyon, France.

Background: Lung ultrasound can accurately detect pandemic coronavirus disease (COVID-19) pulmonary lesions. A lung ultrasound score (LUS) was developed to improve reproducibility of the technique.

Objectives: To evaluate the clinical value of LUS monitoring to guide COVID-19-associated acute respiratory distress syndrome (ARDS) management.

Methods: We conducted a single center, prospective observational study, including all patients admitted with COVID-19-associated ARDS between March and April 2020. A systematic daily LUS evaluation was performed.

Results: Thirty-three consecutive patients were included. LUS was significantly and negatively correlated to P/F. LUS increased significantly over time in non-survivors compared to survivors. LUS increased in 83% of ventilatory associated pneumonia (VAP) episodes, when compared to the previous LUS evaluation. LUS was not significantly higher in patients presenting post-extubation respiratory failure.

Conclusions: In conclusion, our study demonstrates that LUS variations are correlated to disease severity and progression, and LUS monitoring could contribute to the early diagnosis of VAPs.
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http://dx.doi.org/10.1016/j.hrtlng.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165084PMC
August 2021

Symptoms of Mental Health Disorders in Critical Care Physicians Facing the Second COVID-19 Wave: A Cross-Sectional Study.

Chest 2021 09 21;160(3):944-955. Epub 2021 May 21.

Medical Intensive Care Unit, AP-HP, Saint Louis University Hospital, Paris, France.

Background: Working in the ICU during the first COVID-19 wave was associated with high levels of mental health disorders.

Research Question: What are the mental health symptoms in health care providers (HCPs) facing the second wave?

Study Design And Methods: A cross-sectional study (October 30-December 1, 2020) was conducted in 16 ICUs during the second wave in France. HCPs completed the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised (for post-traumatic stress disorder), and the Maslach Burnout Inventory.

Results: Of 1,203 HCPs, 845 responded (70%) (66% nursing staff, 32% medical staff, 2% other professionals); 487 (57.6%) had treated more than 10 new patients with COVID-19 in the previous week. Insomnia affected 320 (37.9%), and 7.7% were taking a psychotropic drug daily. Symptoms of anxiety, depression, post-traumatic stress disorder, and burnout were reported in 60.0% (95% CI, 56.6%-63.3%), 36.1% (95% CI, 32.9%-39.5%), 28.4% (95% CI, 25.4%-31.6%), and 45.1% (95% CI, 41.7%-48.5%) of respondents, respectively. Independent predictors of such symptoms included respondent characteristics (sex, profession, experience, personality traits), work organization (ability to rest and to care for family), and self-perceptions (fear of becoming infected or of infecting family and friends, feeling pressure related to the surge, intention to leave the ICU, lassitude, working conditions, feeling they had a high-risk profession, and "missing the clapping"). The number of patients with COVID-19 treated in the first wave or over the last week was not associated with symptoms of mental health disorders.

Interpretation: The prevalence of symptoms of mental health disorders is high in ICU HCPs managing the second COVID-19 surge. The highest tiers of hospital management urgently need to provide psychological support, peer-support groups, and a communication structure that ensure the well-being of HCPs.
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http://dx.doi.org/10.1016/j.chest.2021.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137352PMC
September 2021

Burden of critically ill patients with influenza in a French catchment population.

Sci Rep 2021 05 18;11(1):10526. Epub 2021 May 18.

Service de Médecine Intensive-Réanimation, Hospices Civils de Lyon, Hôpital Edouard Herriot, 5, place d'Arsonval, 69437 Lyon Cedex 03, 69003, Lyon, France.

Despite the particular focus given to influenza since the 2009 influenza A(H1N1) pandemic, true burden of influenza-associated critical illness remains poorly known. The aim of this study was to identify factors influencing influenza burden imposed on intensive care units (ICUs) in a catchment population during recent influenza seasons. From 2008 to 2013, all adult patients admitted with a laboratory-confirmed influenza infection to one of the ICUs in the catchment area were prospectively included. A total of 201 patients (mean age: 63 ± 16, sex-ratio: 1.1) were included. The influenza-related ICU-bed occupancy rate averaged 4.3% over the five influenza seasons, with the highest mean occupancy rate (16.9%) observed during the 2012 winter. In-hospital mortality for the whole cohort was 26%. Influenza A(H1N1)pdm infections (pdm in the mentioned nomenclature refers to Pandemic Disease Mexico 2009), encountered in 51% of cases, were significantly associated with neither longer length of stay nor higher mortality (ICU and hospital) when compared to infections with other virus subtypes. SOFA score (OR, 1.12; 95% CI, 1.04-1.29) was the only independent factor significantly associated with a prolonged hospitalization. These results highlight both the frequency and the severity of influenza-associated critical illness, leading to a sustained activity in ICUs. Severity of the disease, but not A(H1N1)pdm virus, appears to be a major determinant of ICU burden related to influenza.
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http://dx.doi.org/10.1038/s41598-021-89912-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131583PMC
May 2021

Day-90 survival in critically-ill patients with COVID-19 and hydroxychloroquine: a propensity analysis.

Ann Transl Med 2021 Apr;9(7):524

Medical Intensive Care Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France.

Background: There are limited data on the effect of hydroxychloroquine on medium term outcomes in patients with coronavirus disease 2019 (COVID-19) requiring intensive care. We aimed to evaluate the effects of hydroxychloroquine on day 90 mortality in this specific population.

Methods: This retrospective, multicenter, propensity matched cohort analysis, used data of adult patients with laboratory confirmed COVID-19 admitted to 3 university affiliated intensive care units between March 7, 2020, to April 7, 2020 in Lyon, France. Patients received either hydroxychloroquine (loading dose of 400 mg twice daily at day 1 followed by 200 mg twice daily from day 2 to day 10) or standard of care without hydroxychloroquine. We compared all-cause mortality at day-90 after ICU admission between propensity score matched groups receiving hydroxychloroquine or standard of care.

Results: A total of 157 patients were included with a day-28 and day-90 mortality rate of 23.6% and 32.5%, respectively. The median (interquartile) age was 67 years (56-76 years), 105 (66.9%) were men, 65 (41.4%) fulfilled criteria for acute respiratory distress syndrome, and 64 (41%) received hydroxychloroquine (HCQ) for 10 days (4-10 days). In the propensity score matched cohort (59 patients in each group), day-90 mortality was 35.6% for patients who received HCQ and 23.7% for patients who did not (P=0.23). Kaplan Meier survival analysis showed no statistically significant association between HCQ therapy and mortality (P=0.20 by log-rank test).

Conclusions: In this study, off-label use of HCQ in critically ill patients with COVID-19 was not associated with any significant change in medium-term prognosis, confirming results of studies in less severe patients.
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http://dx.doi.org/10.21037/atm-20-7811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105785PMC
April 2021

Regional lung viscoelastic properties in supine and prone position in a porcine model of acute respiratory distress syndrome.

J Appl Physiol (1985) 2021 07 13;131(1):15-25. Epub 2021 May 13.

Université de Grenoble, Grenoble, France.

Regional viscoelastic properties of thoracic tissues in acute respiratory distress syndrome (ARDS) and their change with position and positive end-expiratory pressure (PEEP) are unknown. In an experimental porcine ARDS, dorsal and ventral lung (R,L and E,L) and chest wall (R,cw and E,cw) viscoelastic resistive (R) and elastic (E) parameters were measured at 20, 15, 10, and 5 cmHO PEEP in supine and prone position. E and R were obtained by fitting the decay of pressure after end-inspiratory occlusion to the equation: P (t) =R e, where t is the length of occlusion and τ time constant. E was equal to R/τ. R,cw and E,cw were measured from esophageal, dorsal, and ventral pleural pressures. Global R,L and E,L were obtained from the global transpulmonary pressure (airway pressure-esophageal pressure), and regional R,L and E,L from the dorsal and ventral airway pressure-pleural pressure difference. Lung ventilation was measured by electrical impedance tomography (EIT). Global R,cw and E,cw did not change with PEEP or position. Global R,L [median(Q1-Q3)] was 37.1 (11.0-65.1), 5.1 (4.3-5.5), 12.1 (8.4-19.5), and 41.0 (26.6-53.5) cmHO/L/s in supine, and 15.3 (9.1-41.9), 7.9 (5.7-11.0), 8.0 (5.1-12.1), and 12.9 (6.4-19.4) cmHO/L in prone from 20 to 5 cmHO PEEP ( = 0.06 for PEEP and = 0.06 for position). Dorsal R,L significantly and positively correlated with the amount of collapse measured with EIT. Global and regional lung and chest wall viscoelastic parameters can be described by a simple rheological model. Regional E and R were uninfluenced by PEEP and position except for PEEP on dorsal E,L and position on dorsal E,cw. In a porcine model of acute respiratory distress syndrome, data were successfully fitted to a rheological model of the nonlinear behavior of viscoelastic properties of lung and chest wall at different positive end-expiratory pressure (PEEP) in the supine and prone position. Prone position tended to decrease lung viscoelastic resistive component. PEEP had a significant effect on dorsal lung viscoelastic elastance. Finally, lung viscoelastic resistance correlated with the amount of lung collapse assessed by electrical impedance tomography.
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http://dx.doi.org/10.1152/japplphysiol.00104.2021DOI Listing
July 2021

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BMJ Open 2021 05 11;11(5):e045041. Epub 2021 May 11.

Service de Médecine Intensive Réanimation, Centre Hospitalier de Valenciennes, Valenciennes, France.

Introduction: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.

Methods And Analysis: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.

Ethics And Dissemination: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT03573739.
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http://dx.doi.org/10.1136/bmjopen-2020-045041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117996PMC
May 2021
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