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1. Inadequate intensive care physician supply in France: a point-prevalence prospective study

Author

Sacha Sarfati, Stephan Ehrmann, Dominique Vodovar, Boris Jung, Nadia Aissaoui, Cédric Darreau, Wulfran Bougouin, Nicolas Deye, Hatem Kallel, Khaldoun Kuteifan, Charles-Edouard Luyt, Nicolas Terzi, Thierry Vanderlinden, Christophe Vinsonneau, Grégoire Muller, Christophe Guitton, CEMIR (Collège des Enseignants de Médecine Intensive Réanimation, French National College of Intensive Care Scholars), and CNP MIR. (Conseil National Professionel de Médecine Intensive Réanimation, French National Council of Intensive Care Medicine)

Subjects
ICU, Intensivist, Medical staffing, Physician shortage, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities. Results Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements. Conclusion The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.

Published
2024
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2. Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024

Author

Nicolas de Prost, Etienne Audureau, Antoine Guillon, Lynda Handala, Sébastien Préau, Aurélie Guigon, Fabrice Uhel, Quentin Le Hingrat, Flora Delamaire, Claire Grolhier, Fabienne Tamion, Alice Moisan, Cédric Darreau, Jean Thomin, Damien Contou, Amandine Henry, Thomas Daix, Sébastien Hantz, Clément Saccheri, Valérie Giordanengo, Tài Pham, Amal Chaghouri, Pierre Bay, Jean-Michel Pawlotsky, Slim Fourati, and the SEVARVIR investigators

Subjects
SARS-CoV-2, Omicron, Subvariant, JN.1, Acute respiratory failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. Methods The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). Results During the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). Conclusions Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

Published
2024
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3. Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID)

Author

Luc Desmedt, Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Johann Auchabie, Julien Lorber, Béatrice La Combe, Pierre Kergoat, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Ergreteau, Philippe Seguin, Maëlle Martin, Jean Reignier, Jean-Baptiste Lascarrou, and Emmanuel Canet

Subjects
Invasive pulmonary aspergillosis, COVID‑19, Mechanical ventilation, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. Methods We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. Results The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0–27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00–1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32–3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. Conclusion Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality. Graphical Abstract

Published
2024
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4. Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study

Author

Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Charly Dano, Julien Lorber, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Egreteau, Philippe Seguin, Jean Reignier, Jean-Baptiste Lascarrou, and Emmanuel Canet

Subjects
COVID-19, Dexamethasone, Mortality, Intubation, Ventilator-associated pneumonia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Key messages What is already known on this topic Dexamethasone decreased day-28 mortality in the randomised controlled trial RECOVERY in patients admitted for COVID-19, including 74% who required oxygen and 16% invasive mechanical ventilation (iMV). Other trials targeting critically ill patients did not replicate this finding, leaving uncertainty about the benefits of dexamethasone. What this study adds In our large observational cohort of critically ill COVID-19 patients, of whom 61% required iMV, early systemic dexamethasone was not associated with lower day-28 mortality compared to no steroids. However, early dexamethasone was associated with less need for iMV, more days alive and off iMV, and a higher frequency of ventilator-associated pneumonia in the iMV sub-group. How this study might affect research, practice, or policy This study suggests that early dexamethasone may be warranted in critically ill COVID-19 patients, provided those receiving iMV are monitored closely for ventilatory-associated pneumonia.

Published
2022
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5. Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS

Author

Pauline Lamouche-Wilquin, Jérôme Souchard, Morgane Pere, Matthieu Raymond, Pierre Asfar, Cédric Darreau, Florian Reizine, Baptiste Hourmant, Gwenhaël Colin, Guillaume Rieul, Pierre Kergoat, Aurélien Frérou, Julien Lorber, Johann Auchabie, Béatrice La Combe, Philippe Seguin, Pierre-Yves Egreteau, Jean Morin, Yannick Fedun, Emmanuel Canet, Jean-Baptiste Lascarrou, and Agathe Delbove

Subjects
Mechanical ventilation, SARS-CoV-19, Nosocomial pneumonia, Dexamethasone, Methylprednisolone, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Rationale Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. Objectives To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). Methods We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. Measurements and main results Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05–1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61; P = 0.0003). Conclusions Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Published
2022
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6. Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial

Author

Djillali, ANNANE, Christian, BRUN-BUISSON, Benoit, MISSET, Jean, CHASTRE, François, BRIVET, Julien, BOHE, Carole, SCHWEBEL, Shidasp, SIAMI, Michel, SLAMA, Olivier, LEROY, Gilles, CAPELLIER, Michel, WOLFF, Mohamed, ALI BEN ALI, François, ANTONINI, Jean-François, LORIFERNE, Franck, PETITPAS, Claire, CHARPENTIER, Jean-Michel, CONSTANTIN, Gilles, D'HONNEUR, Bertrand, SOUWEINE, Xavier, FORCEVILLE, Bruno, MEGARBANE, Francois, BAUDIN, Gwenhaël, COLIN, Karim, ASEHNOUNE, Jean-Pierre, QUENOT, Bruno, FRANCOIS, Thierry, BOULAIN, Emmanuelle, MERCIER, Jean, REIGNIER, Roland, AMATHIEU, Fabrice, COOK, Alain, CARIOU, Loic, CHIMOT, Fouad, Fadel, Andrea, Polito, Bernard, Clair, Virginie, Maxime, David, Luis, Tarek, Sharshar, David, Orlikowski, Keyvan, RAZAZI, Nicolas, DE PROST, Guillaume, CARTEAUX, Maité, GARROUSTE ORGEAS, François, Philippart, Alain, Combes, Ania, Nieszkowska, Frederic, Jacobs, Dominique, Prat, Patrick, Lafforgue, Claire, ARA SOMOHANO, Clémence, MINET, Maxime, LUGOSI, Julien, Maizel, Jean Christophe, Navellou, Bruno, Mourvillier, Lila, Bouadma, Jean François, Timsit, Claude Denis, Martin, Julien, Textoris, Sandrine, Wiramus, Clément, BRUN, Benoît, RAGONNET, Ali, Ait-Hssain, Samia, Touati, Jean, Kuba, Vincent, Willems, Pierre, Lahillaire, Mohammed, Lassi, Marion, ANTONA, Alia, MEGHENEM, Marine, DEMESMAY, Eric, Boulet, Olivier, LOUTREL, Romain, DUMONT, Antoine, ROQUILLY, Pierre-Joachim, MAHE, Dominique, DEMEURE dit LATTE, Philippe, CHAMPIN, Jean François, ARNOULD, Raphaël, CINOTTI, Ronan, Le FLOCH, Marc, Clavel, Philippe, Vignon, Nicolas, Pichon, Emmanuelle, BEGOT, Anne-Laure, FEDOU, Catherine, CHAPELLAS, Antoine, GALY, Dalila, Benzekri Lefevre, Armelle, Mathonnet, Anne, Bretagnol, Isabelle, Runge, François, BARBIER, Grégoire, MULLER, Denis, GAROT, Pierre François, DEQUIN, Dominique, PERROTIN, Annick, LEGRAS, Julie, MANKIKIAN, Patrice, TALEC, Stephan, EHRMANN, Aurélie, JORET, Claire, LHOMMET, Emmanuelle, ROUVE, Laetitia, BODET-CONTENTIN, Youenn, JOUAN, Charlotte, SALMONGANDONNIERE, Laurent, MARTIN-LEFEVRE, Matthieu, HENRY-LAGARRIGUE, Aihem, YEHIA, Jean-Baptiste, LASCARROU, Christine, LEBERT, Jean-Claude, LACHERADE, Eric, LEVESQUE, Yen-Lan, NGUYEN, Fabrice, DAVIAUD, Adrien, BOUGLE, Jean Paul, MIRA, Jean Daniel, CHICHE, Frederic, PENE, Tristan, MORICHAU-BEAUCHANT, Guillaume, GERI, Pierre Henri, DESSALLES, Yannick, MONSEAU, Mélanie, SAINT-LEGER, Sandrine, BEDON-CARTE, Laetitia, Bodet-Contentin, Walid, Darwiche, Stephan, Ehrmann, Denis, Garot, Antoine, Guillon, Youenn, Jouan, Annick, Legras, Julie, Mankikian, Emmanuelle, Mercier, Marlene, Morisseau, Yonatan, Perez, Emmanuelle, Rouve, Charlotte, Salmon-Gandonniere, Julie, Helms, Hassene, Rahmani, Alexandra, Monnier, Hamid, Merdji, Raphael, Clere-Jehl, Laure, Stiel, Antoine, Studer, Pascal, Andreu, Jean-Baptiste, Roudaut, Marie, Labruyere, Marine, Jacquier, Francois, Barbier, Dalila, Benzekri, Thierry, Boulain, Sophie, Jacquier, Gregoire, Muller, Mai-Anh, Nai, Sophie, Tollec, Damien, Roux, Jonathan, Messika, Constance, Vuillard, Louis-Marie, Dumont, Laura, Federici, Noemie, Zucman, Marc, Amouretti, Djillali, Annane, Pierre, Moine, Paris, Meng, Rania, Bounab, Muriel-Sarah, Fartoukh, Michel, Djibre, Alexandre, Elabbadi, Marie-Ange, Azais, Konstantinos, Bachoumas, Arthur, Bailly, Remi, Bernardon, Gauthier, Blonz, Luc, Desmedt, Brian, Emonet, Maud, Fiancette, Matthieu, Henry, Jean-Claude, Lacherade, Jean-Baptiste, Lascarrou, Christine, Lebert, Julien, Lorber, Laurent Martin-, Lefevre, Caroline, Pouplet, Isabelle, Vinatier, Aihem, Yehia, Sarah, Benghanem, Julien, Charpentier, Clara, Vigneron, Anne-Laure, Fedou, Claire, Mancia, Emmanuelle, Begot, Thomas, Daix, Antoine, Galy, Celine, Gonzalez, Marine, Goudelin, Bruno, Evrard, Arnaud, Desachy, Julien, Vaidie, Guillaume, Gilbert, Cedric, Darreau, Benoit, Derrien, Marjorie, Saint-Martin, Patrice, Tirot, Mickael, Landais, Nicolas, Chudeau, Jean Christophe, Callahan, Dominique, Vivier, Charlene, Le Moal, Pierre-Yves, Olivier, Remy, Marnai, Francis, Schneider, Nicolas, Sedillot, Xavier, Tchenio, Adrien, Robine, Yves, Poncelin, Remi, Bruyere, Heming, Nicholas, Renault, Alain, Kuperminc, Emmanuelle, Brun-Buisson, Christian, Megarbane, Bruno, Quenot, Jean-Pierre, Siami, Shidasp, Cariou, Alain, Forceville, Xavier, Schwebel, Carole, Leone, Marc, Timsit, Jean-Francois, Misset, Benoît, Benali, Mohamed Ali, Colin, Gwenhael, Souweine, Bertrand, Asehnoune, Karim, Mercier, Emmanuelle, Chimot, Loïc, Charpentier, Claire, François, Bruno, Boulain, Thierry, Petitpas, Frank, Constantin, Jean Michel, Dhonneur, Gilles, Baudin, François, Combes, Alain, Bohé, Julien, Loriferne, Jean-François, Cook, Fabrice, Slama, Michel, Leroy, Olivier, Capellier, Gilles, Dargent, Auguste, Hissem, Tarik, Bounab, Rania, Maxime, Virginie, Moine, Pierre, Bellissant, Eric, and Annane, Djillali

Published
2024
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7. Indications et délai de l’intubation orotrachéale en réanimation : état des lieux

Author

Cédric Darreau, Agathe Delbove, Sophie Jacquier, Marjorie Saint-Martin, François-Michel Beloncle, Nicolas Lerolle, and Frédéric Martino

Subjects
Emergency Medicine, Emergency Nursing
Abstract

L’intubation oro-trachéale et la ventilation mécanique font partie de l’arsenal thérapeutique courant en médecine intensive et réanimation. Elles visent à suppléer une défaillance respiratoire et peuvent être associées à la prise en charge de défaillances neurologiques ou hémodynamiques. Néanmoins l’intubation et la ventilation mécanique sont associées à des effets indésirables potentiellement graves. Les indications ne sont pas toujours bien codifiées, la question du délai de l’intubation est rarement abordée dans les recommandations et les différences de pratiques entre les centres ou les praticiens prennent une place importante dans le processus de décision. Au-delà de l’indication, le choix du bon moment pour l’intubation doit prendre en compte rapport bénéfice risque de la ventilation invasive ainsi qu’un bénéfice potentiel à éviter une intubation inutile mais qui s’associe à un risque d’intubation trop tardive. Dans cette mise au point, nous proposons une revue des données de la littérature sur la place et le délai de l’intubation oro-trachéale dans la prise en charge des défaillances respiratoires, hémodynamiques et neurologiques les plus fréquemment rencontrées en médecine intensive et réanimation.

Published
2022
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8. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

Author

David Hajage, Alain Combes, Christophe Guervilly, Guillaume Lebreton, Alain Mercat, Arthur Pavot, Saad Nseir, Armand Mekontso-Dessap, Nicolas Mongardon, Jean Paul Mira, Jean-Damien Ricard, Alexandra Beurton, Guillaume Tachon, Loay Kontar, Christophe Le Terrier, Jean Christophe Richard, Bruno Mégarbane, Ruth H. Keogh, Aurélien Belot, Camille Maringe, Clémence Leyrat, Matthieu Schmidt, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W. Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, Sébastian Voicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Meriam Lamraoui, Claire Alessandri, Quentin de Roux, Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien Pili Floury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris-Saclay, CHU Lille, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS [Créteil] (UPEC/Faculté de Médecine de Créteil), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Foch [Suresnes], CHU Amiens-Picardie, Geneva University Hospital (HUG), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], London School of Hygiene and Tropical Medicine (LSHTM), RICHARD, Jean-Christophe, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, Adult, Respiratory Distress Syndrome, SARS-CoV-2, [SDV]Life Sciences [q-bio], acute respiratory distress syndrome (ARDS), COVID-19, extracorporeal membrane oxygenation, Critical Care and Intensive Care Medicine, Cohort Studies, [SDV] Life Sciences [q-bio], emulated target trial, acute respiratory distress syndrome, Treatment Outcome, surgical procedures, operative, Humans, Retrospective Studies
Abstract

International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2

Published
2022
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9. Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial

Author

Bruno François, Simon Lambden, Jean-Jacques Garaud, Marc Derive, Jean-Marie Grouin, Pierre Asfar, Cédric Darreau, Jean-Paul Mira, Jean-Pierre Quenot, Jérémie Lemarié, Emmanuelle Mercier, Jean-Claude Lacherade, Christophe Vinsonneau, Tom Fivez, Julie Helms, Julio Badie, Mitchell Levy, Valérie Cuvier, Margarita Salcedo-Magguilli, Anne-Lise Laszlo-Pouvreau, Pierre-François Laterre, and Sébastien Gibot

Subjects
General Medicine
Published
2023
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10. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial

Author

Stephan Ehrmann, Jie Li, Miguel Ibarra-Estrada, Yonatan Perez, Ivan Pavlov, Bairbre McNicholas, Oriol Roca, Sara Mirza, David Vines, Roxana Garcia-Salcido, Guadalupe Aguirre-Avalos, Matthew W Trump, Mai-Anh Nay, Jean Dellamonica, Saad Nseir, Idrees Mogri, David Cosgrave, Dev Jayaraman, Joan R Masclans, John G Laffey, Elsa Tavernier, Ahmad A Elshafei, Brady J Scott, Tyler Weiss, Ramandeep Kaur, Lauren J Harnois, Amanda Miller, Flor Cerda, Andrew Klein, Jacob R Burd, Kathleen Posa-Kearney, Matthew Trump, Julie Jackson, Trevor Oetting, Mark Greenwood, Lindsay Hazel, Lisa Kingery, Lindsey Morris, Joon Yong Moon, Julianne Garnett, Shijing Jia, Kristine Nelson, Camilla Giacomini, John Laffey, Aoife Brennan, Conor Judge, Maeve Kernan, Claire Kelly, Ritika Ranjan, Siobhan Casey, Kevin O'Connell, Evelyn Newell, David Gallagher, Alistair Nichol, Ger Curley, Miguel Ibarra Estrada, Roxana García-Salcido, Alexandra Vargas-Obieta, Sara A Aguirre-Díaz, Luz Alcántar-Vallín, Montserrat Alvarado-Padilla, Quetzalcóatl Chávez-Peña, José A López-Pulgarín, Julio C Mijangos-Méndez, Miguel Marín-Rosales, Jorge E García-Alvarado, Oscar G Baltazar-González, Maura C González-Guerrero, Paola G Gutiérrez Ramírez, Sean Gilman, Patrice Plamondon, Rachel Roy, Jason Shahin, Raham Ragoshai, Aasmine Kaur, Josie Campisi, Joseph Dahine, Stefanie Perron, Slimane Achouri, Ronald Racette, Anne Kulenkamp, Andrés Pacheco, Marina García-de-Acilu, Irene Dot, Laetitia Bodet-Contentin, Denis Garot, Emmanuelle Mercier, Charlotte Salmon Gandonnière, Marlène Morisseau, Youenn Jouan, Walid Darwiche, Annick Legras, Antoine Guillon, Pierre-François Dequin, Anne-Charlotte Tellier, Jean Reignier, Jean-Baptiste Lascarrou, Amélie Seguin, Luc Desmedt, Emmanuel Canet, Christophe Guitton, Rémy Marnai, Jean-Christophe Callahan, Mickaël Landais, Nicolas Chudeau, Cédric Darreau, Patrice Tirot, Marjorie Saint Martin, Charlene Le Moal, Grégoire Muller, Sophie Jacquier, Gwenaël Prat, Pierre Bailly, Nicola Ferrière, Arnaud W Thille, Jean-Pierre Frat, Clément Saccheri, Matthieu Buscot, Gaëtan Plantefève, Damien Contou, Damien Roux, Jean-Damien Ricard, Laura Federici, Noémie Zucman, Santiago Freita Ramos, Marc Amouretti, Sébastien Besset, Coralie Gernez, Agathe Delbove, Guillaume Voiriot, Alexandre Elabbadi, Muriel Fartoukh, Sébastien Préau, Raphaël Favory, Alexandre Pierre, Arnaud Sement, Nicolas Terzi, Florian Sigaud, Clara Candille, Emanuele Turbil, Julien Maizel, Clément Brault, Yoan Zerbib, Aurélie Joret, Cédric Daubin, Laurent Lefebvre, Alais Giraud, Adrien Auvet, Christophe Vinsonneau, Mehdi Marzouk, Jean-Pierre Quenot, Pascal Andreu, Marie Labruyère, Jean-Baptiste Roudaut, François Aptel, Alexandre Boyer, Philippe Boyer, Jean-Claude Lacherade, Hugo Hille, Marie Bouteloup, Matthieu Jeannot, Marc Feller, Guillaume Grillet, Bruno Levy, Antoine Kimmoun, Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Pulmonary and Respiratory Medicine, Canada, medicine.medical_specialty, medicine.medical_treatment, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Patient Positioning, 03 medical and health sciences, 0302 clinical medicine, Correspondence, Prone Position, medicine, Humans, Intubation, Prospective Studies, 030212 general & internal medicine, Wakefulness, Mexico, ComputingMilieux_MISCELLANEOUS, SARS-CoV-2, business.industry, Incidence (epidemiology), Hazard ratio, COVID-19, United States, 3. Good health, Prone position, Treatment Outcome, 030228 respiratory system, Respiratory failure, Spain, Relative risk, Emergency medicine, Observational study, France, Respiratory Insufficiency, business, Ireland, Nasal cannula
Abstract

Summary Background Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. Methods In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov , NCT04325906 , NCT04347941 , NCT04358939 , NCT04395144 , NCT04391140 , and NCT04477655 . Findings Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75−0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62−0·91), and the HR for mortality was 0·87 (0·68−1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. Interpretation Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. Funding Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interregional, Appel d'Offre 2020, Groupement Interregional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion a Tours de la Reanimation Medicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.

Published
2021
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11. Does Chloride Intake at the Early Phase of Septic Shock Resuscitation Impact on Renal Outcome?

Author

Thibault Balzer, Agathe Delbove, Marjorie Saint-Martin, Olivier Huet, Nicolas Lerolle, Xavier Chapalain, Cédric Darreau, Pierre-Yves Egreteau, Cecile Aubron, Sophie Jacquier, and Frédéric Martino

Subjects
Male, Resuscitation, Critical Care, Organ Dysfunction Scores, medicine.medical_treatment, Hemodynamics, Renal function, Critical Care and Intensive Care Medicine, Sepsis, Chlorides, medicine, Humans, Hospital Mortality, Prospective Studies, Propensity Score, Saline, Aged, Aged, 80 and over, Septic shock, business.industry, Acute kidney injury, Acute Kidney Injury, Length of Stay, Middle Aged, medicine.disease, Shock, Septic, Renal Replacement Therapy, Survival Rate, Anesthesia, Emergency Medicine, Fluid Therapy, SOFA score, Female, business
Abstract

Fluid administration is one of the first lines of treatment for hemodynamic management of sepsis and septic shock. Studies investigating the effects of chloride-rich fluids including normal saline on renal function report controversial findings.This is a prospective, observational, multicenter study. Patients with septic shock, defined according to Sepsis-2 definition, were eligible. A "high-dose" of chloride was defined as a chloride intake greater than 18 g administrated within the first 48 h of septic shock management. The purpose of this study was to investigate the impact of cumulative chloride infusion within the first 48 h of septic shock resuscitation on acute kidney injury (AKI).Two hundred thirty-nine patients with septic shock were included. Patients who received a "high-dose" of chloride had significantly higher Sequential Organ Failure Assessment score at the time of enrolment (P 0.001). Cumulative chloride load was higher in patients requiring renal replacement therapy (RRT) (31.1 vs. 25.2 g/48 h; P 0.005). Propensity score-weighted regression did not find any association between "high-dose" of chloride and AKI requiring RRT (OR: 0.97 [0.88-1.1]; P = 0.69). There was no association between "high-dose" of chloride and worsening kidney function at H48 (OR: 0.94 [0.83-1.1]; P = 0.42). There was also no association between "high-dose" of chloride and ICU length of stay (P = 0.61), 28-day mortality (P = 0.83), or hospital mortality (P = 0.89).At the early stage of resuscitation of critically ill patients with septic shock, administration of "high-dose" of chloride (18 g/48 h) was not associated with renal prognosis.

Published
2021

12. Impact of endotracheal intubation on septic shock outcome: A post hoc analysis of the SEPSISPAM trial

Author

Jean François Hamel, Agathe Delbove, Pierre Asfar, Nicolas Lerolle, and Cédric Darreau

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Critical Care, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Severity of Illness Index, Intensive care, Fraction of inspired oxygen, Severity of illness, Intubation, Intratracheal, medicine, Humans, Intubation, Aged, Retrospective Studies, Aged, 80 and over, Immunosuppression Therapy, Septic shock, business.industry, Mortality rate, Glasgow Coma Scale, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Shock, Septic, Surgery, Oxygen, Intensive Care Units, Treatment Outcome, Anesthesia, Multivariate Analysis, Female, business
Abstract

Introduction The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients. Methods This is a post hoc analysis of the database of the SEPSISPAM study, including patients with septic shock. Results Among the 776 patients, 633 (82%) were intubated within 12 hours of study inclusion (early intubation), 113 (15%) were never intubated, and 30 (4%) had delayed intubation. Intensive care units (ICUs) were classified according to frequency of early intubation: early intubation less than 80% of patients (lowest frequency: 7 ICUs, 254 patients), 80% to 90% (middle frequency: 5 ICUs, 170 patients), and greater than 90% (highest frequency: 6 ICUs, 297 patients). Type of ICU, pulmonary infection, lactate greater than 2 mmol/L, lower Pao 2 /fraction of inspired oxygen ratio, lower Glasgow score, and absence of immunosuppression were independently associated with early intubation. Patients never intubated had a lower initial severity and a low mortality rate. In comparison to patients intubated early, patients with delayed intubation had had fewer days alive without organ support by day 28. Intensive care units with the highest frequency of early intubation had a higher mortality rate in comparison to ICUs with middle frequency of early intubation. A nonsignificant increased mortality was observed in ICU with lowest frequency of early intubation. Conclusions Practices regarding the place of endotracheal intubation in septic shock may impact outcome.

Published
2015
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13. Anticoagulation strategy and safety in critically ill COVID-19 patients: a French retrospective multicentre study

Author

Pauline Lamouche-Wilquin, Léa Perrin, Morgane Pere, Matthieu Raymond, Pierre Asfar, Cedric Darreau, Florian Reizine, Gwenhaël Colin, Agathe Delbove, Johann Auchabie, Baptiste Hourmant, Aurélien Frérou, Béatrice La Combe, Jean Morin, Pierre Kergoat, Julien Lorber, Pierre-Yves Egreteau, Jérome Souchard, Emmanuel Canet, and Jean-Baptiste Lascarrou

Subjects
COVID-19, Anticoagulation strategies, Venous thromboembolism, Deep vein thrombosis, Pulmonary embolism, Intensive care unit, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Background Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. Methods We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. Results Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52–1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79–1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38–0.80; p

Published
2023
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14. Early intubation and patient-centered outcomes in septic shock: a secondary analysis of a prospective multicenter study

Author

Ricard Mellado-Artigas, Carlos Ferrando, Frédéric Martino, Agathe Delbove, Bruno L. Ferreyro, Cedric Darreau, Sophie Jacquier, Laurent Brochard, and Nicolas Lerolle

Subjects
Septic shock, Outcomes, Tracheal intubation, Mechanical ventilation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Purpose Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay. Methods This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping. Results A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86–2.39, p = 0.16). ICU and hospital length of stay were not different among groups [9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI − 7 to 8) days]. All sensitivity analyses confirmed the robustness of our findings. Conclusions An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings. Trial registration NCT02780466. Registered on May 19, 2016.

Published
2022
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15. Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial

Author

Shidasp Siami, Charlène Le Moal, Thomas DAIX, Sylvie Chevret, Yonatan Perez, Constance Vuillard, Damien Roux, Jonathan Messika, Stephan Ehrmann, Jean-Pierre Quenot, Dalila Benzekri, Gwenhaël Colin, Thierry Boulain, Julie Mankikian, Laura Federici, Jean Reignier, Jean-Paul Mira, Marie-Ange Azais, Djillali Annane, Jean-Claude Lacherade, Grégoire Muller, Christine Lebert, Nicholas Heming, Arthur Bailly, Emmanuelle Mercier, Jean-Baptiste Lascarrou, Julio Badie, Louis-Marie Dumont, Gaetan Plantefeve, Francis Schneider, Patrice Tirot, Isabelle Vinatier, Mickael Landais, Michel Djibré, Bruno Francois, Alexandra Monnier, Francois Barbier, Ferhat Meziani, Hamid Merdji, Pascal Andreu, Julie Helms, Laetitia Bodet-Contentin, Nicolas Pichon, Noémie Zucman, Mehran Monchi, Xavier Monnet, Marie Labruyère, Denis Garot, Hassène Rahmani, Jérôme Fleuriet, Pierre-Louis Declerq, Adrien Robine, Fabrice Uhel, Charles Cerf, Gilles Troché, Alexandrou Antigoni, Annane Djillali, Arlt Birte, Badie Julio, Benghanem Sarah, Berdaguer Ferrari Fernando, Cerf Charles, Chelly Dagdia Zaineb, Chevret Sylvie, Colin Gwenhaël, Daniel Christel, Declercq Pierre-Louis, Delbove Agathe, Devillier Philippe, Fleuriet Jérome, François Bruno, Garchon Henri-Jean, Godot Véronique, Grassin-Delyle Stanislas, Grisolia Mathieu, Guitton Christophe, Helms Julie, Heming Nicholas, Herzog Marielle, Kamel Toufik, Kedad Zoubida, Lassalle Philippe, Lhermite Guillaume, Megarbane Bruno, Mekontso Dessap Armand, Mercier Emmanuelle, Meziani Ferhat, Mira Jean-Paul, Monchi Mehran, Monnet Xavier, Muller Grégoire, Quenot Jean-Pierre, Reignier Jean, Robine Adrien, Rottman Martin, Roux Anne-Laure, Schneider Francis, Siami Shidasp, Tissieres Pierre, Troché Gilles, Uhel Fabrice, Zeitouni Karine, Plantefève Gaëtan, Walid Darwiche, Antoine Guillon, Youenn Jouan, Annick Legras, Marlene Morisseau, Emmanuelle Rouve, Charlotte Salmon-Gandonniere, Raphael Clere-Jehl, Laure Stiel, Antoine Studer, Jean-Baptiste Roudaut, Marine Jacquier, Sophie Jacquier, Armelle Mathonnet, Mai-Anh Nai, Isabelle Runge, Sophie Tollec, Marc Amouretti, Pierre Moine, Paris Meng, Rania Bounab, Muriel-Sarah Fartoukh, Alexandre Elabbadi, Konstantinos Bachoumas, Remi Bernardon, Gauthier Blonz, Luc Desmedt, Brian Emonet, Maud Fiancette, Matthieu Henry, Julien Lorber, Laurent Martin-Lefevre, Caroline Pouplet, Aihem Yehia, Sarah Benghanem, Julien Charpentier, Clara Vigneron, Anne-Laure Fedou, Claire Mancia, Emmanuelle Begot, Philippe Vignon, Antoine Galy, Celine Gonzalez, Marine Goudelin, Bruno Evrard, Arnaud Desachy, Julien Vaidie, Guillaume Gilbert, Cedric Darreau, Benoit Derrien, Marjorie Saint-Martin, Nicolas Chudeau, Jean Christophe Callahan, Dominique Vivier, Pierre-Yves Olivier, Remy Marnai, Nicolas Sedillot, Xavier Tchenio, Yves Poncelin, Remi Bruyere, Grimaldi Lamiae, and Derridj Nawal

Subjects
Medicine
Abstract

Introduction Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids.Methods and analysis RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%–10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids’ effect in each subset, and (2) measure of interaction.Ethics and dissemination The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration number ClinicalTrials.gov Registry (NCT04280497).

Published
2023
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17. Peut-on réduire la prescription des carbapénèmes en réanimation ? Un audit de 107 prescriptions

Author

Cédric Darreau, Frédéric Moal, Jean-Ralph Zahar, Sigismond Lasocki, and Marguerite Le Penndu

Subjects
Anesthesiology and Pain Medicine
Abstract

Introduction L’emergence de bacteries multi-resistantes (BMR) justifie une prescription raisonnee d’antibiotiques. Leur usage inapproprie peut induire la selection ou l’emergence de bacteries resistantes. Les carbapenemes (carba) sont des antibiotiques « de derniers recours » a large spectre qu’il convient de preserver par une prescription limitee. L’objectif de ce travail est d’evaluer la qualite de la prescription de carba et la frequence de la desescalade au 5 e jour dans un service de reanimation. Materiel et methodes Etude retrospective monocentrique, toutes les prescriptions nominatives de carba realisees de janvier 2012 a mai 2014 ont ete extraites de la base de donnee de la pharmacie et les dossiers des patients concernes ont ete etudies. Toutes les donnees concernant le traitement antibiotique et les differents episodes infectieux ont ete colligees. Les prescriptions de carba ont ete classees en probabilistes (P), orientees (O, sur une colonisation ou documentation anterieure a une bacterie dont le mecanisme de resistance justifiait la prescription) ou documentees (D, lorsqu’un prelevement microbiologique de l’infection en cours justifiait la prescription). Les donnees (mediane[Q1–Q3], moyenne ± ET ou n [%]) etaient comparees par des tests non parametriques (Kruskal-Wallis ou test exact de Fischer). Resultats Cent sept prescriptions ont ete analysees, dont 80 (75 %) probabilistes ou orientees [ n = 52 (65 %) et 28 (35 %) pour P et O respectivement] et 27 (25 %) documentees. Les patients des 3 groupes (P, O et D) etaient comparables (âge 64 ± 20 ans, IGS II 52 ± 15, 63 % hommes, 65 % chirurgie urgente). Les sites de l’infection traitee etaient 50 (47 %) poumons, 34 (32 %) abdomen, 8 (7 %) bacteriemies, 5 (5 %) urines, 4 (4 %) SNC, 4 (4 %) inconnus, 2 (2 %) os, sans differences entre les groupes ( p = 0,13). Les prescriptions D etaient plus souvent en journee (89 % vs 61 % et 71 % pour D, P et O, p = 0,04). Parmi les prescriptions P + O evaluables, 53/80 (66 %) etaient desescaladees au 5 e jour. Le maintien des carba a j + 5 sans justificatif microbiologique ne concernait que 12 (17 %) prescriptions P + O. Il n’y avait pas de difference entre les groupes P et O pour la desescalade a j5 ( p = 0,40), meme microbiologiquement justifiee ( p = 0,26), indiquant que la colonisation/infection prealable n’etait pas associee a une meilleure adaptation de la prescription initiale. Aucun critere initial de l’infection (absence de choc, score SOFA a j0 ou j2 de l’infection, baisse des globules blancs a j2, apyrexie, type d’infection…) n’etait associe a la desescalade a j5. La survie a j28 n’etait pas differente entre les 3 groupes (56, 57 et 70 % pour P, O et D, p = 0,47). Chez les patients ayant une infection documentee, 12 (44 %) recevaient une molecule couvrant deja la bacterie causale initialement, sans modification du pronostic ( Fig. 1 ). Discussion Les prescriptions de Carabapenemes dans notre reanimation sont majoritairement non documentees et la connaissance d’une colonisation ou d’une infection anterieure a BMR n’ameliore pas leur adequation. La desescalade etait frequente dans notre pratique, avec seulement 12 (11 % de l’ensemble des prescriptions) prescriptions maintenues a j5 sans justification microbiologique.

Published
2015
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18. Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

Author

Arnaud W, Thille, Arnaud, Gacouin, Rémi, Coudroy, Stephan, Ehrmann, Jean-Pierre, Quenot, Mai-Anh, Nay, Christophe, Guitton, Damien, Contou, Guylaine, Labro, Jean, Reignier, Gael, Pradel, Gaëtan, Beduneau, Laurence, Dangers, Clement, Saccheri, Gwénaël, Prat, Guillaume, Lacave, Nicholas, Sedillot, Nicolas, Terzi, Béatrice, La Combe, Jean-Paul, Mira, Antoine, Romen, Marie-Ange, Azais, Anahita, Rouzé, Jérôme, Devaquet, Agathe, Delbove, Martin, Dres, Jeremy, Bourenne, Alexandre, Lautrette, Joe, de Keizer, Stéphanie, Ragot, Jean-Pierre, Frat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Victor Dupouy, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Henri Mondor d'Aurillac, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Grenoble, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Groupe Hospitalier Bretagne Sud (GHBS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Pau, Centre Hospitalier Loire Vendée Océan, CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Supported by a grant (18-007) from the Programme Hospitalier de Recherche Clinique National 2018 of the French Ministry of Health., REVA Research Network: Anne Veinstein, Delphine Chatellier, Florence Boissier, Maeva Rodriguez, Céline Deletage, Céline Abonneau, Adel Maamar, Florian Reizine, Jean-Marc Tadie, Charlotte Salmon-Gandonniere, Emmanuelle Mercier, Stefan Mankikian, Pascal Andreu, Marine Jacquier, Marie Labruyère, Dalila Benzekri-Lefevre, Grégoire Muller, Armelle Mathonnet, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Gaëtan Plantefève, Paul Desaint, Radj Cally, Pierre Oudeville, Valentin Pointurier, Yannick Rabouel, Gauthier Blonz, Maité Agbakou, Thi My-Hue Nguyen, Marie-Hélène Hausermann, Christophe Girault, Dorothée Carpentier, Chloé Combe, Amélie Renou, Jean Dellamonica, Lucas Morand, Pierre Bailly, Christelle Teiten, Marine Paul, Hugo Bellut, Clio Torres, Camille Bouisse, Guillaume Rigault, Louis-Marie Galerneau, Pierre Bouju, Roland Smoning, Driss Laghlam, Morgane Bertrix, Alexandre Massri, Ugo Gouedard, Saad Nseir, Benjamin Zuber, Yannick Fedun, Côme Bureau, Julien Carvelli, Guillaume Gayraud, Quentin Levrat, Emmanuel Vivier, Christophe Leroy, Laurent Argaud, Alexandre Demoule, Gaetan Beduneau, Jean Dellamonica, Claude Guerin, Samir Jaber, Armand Mekontso-Dessap, Alain Mercat, Saad Nseir, Jean Roeseler, Matthieu Schmidt, Nicolas Terzi, Arnaud W Thille, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), and MORNET, Dominique

Subjects
Positive-Pressure Respiration, [SDV] Life Sciences [q-bio], Recurrence, Respiration, [SDV]Life Sciences [q-bio], Airway Extubation, Humans, General Medicine, Respiratory Insufficiency, Respiration, Artificial, Ventilator Weaning
Abstract

International audience; Background: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

Published
2022
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19. Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

Author

Dres, Martin, Hajage, David, Lebbah, Said, Kimmoun, Antoine, Pham, Tai, Béduneau, Gaëtan, Combes, Alain, Mercat, Alain, Guidet, Bertrand, Demoule, Alexandre, Schmidt, Matthieu, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Saint-Antoine [AP-HP], COVID-ICU investigators: Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Reignier Jean, Seguin Amélie, Garret Charlotte, Canet Emmanuel, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-AhnNay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Marie Anne Melone, Maxime Gauzi, Arnaud Guilbert, Geoffrey Kouadri, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clémet Hoffmann, Nicolas Donat, Violaine Muller, Thibault Martinez, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan L E Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, SqébastianVoicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Nicolas Mongardon, Olivier Langeron, Eric Levesque, Arié Attias, Charles de Roquetaillade, Benjamin G Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, ThiMy Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, RostaneGaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien PiliFloury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Florent Bavozet, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, and dres, martin

Subjects
[SDV] Life Sciences [q-bio], Acute respiratory distress syndrome, Frailty, [SDV]Life Sciences [q-bio], Old patients, COVID-19, Intensive care unit, Mortality, Intubation
Abstract

International audience; Abstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO 2 /FiO 2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO 2 /FiO 2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p

Published
2021
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20. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19

Author

Angus, Derek, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa, Horvat, Christopher, Hullegie, Sebastiaan, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mcauley, Daniel, Mcglothin, Anna, Mcguinness, Shay, Mcverry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger, Mcarthur, Colin, Webb, Steven, Gordon, Anthony, NIHR, Hôpital Raymond Poincaré [AP-HP], Writing Committee for the REMAP-CAP Investigators, Farah Al-Beidh, Derek Angus, Djillali Annane, Yaseen Arabi, Wilma van Bentum-Puijk, Scott Berry, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Allen Cheng, Menno De Jong, Lennie Derde, Lise Estcourt, Herman Goossens, Anthony Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick Lawler, Edward Litton, John Marshall, Colin McArthur, Daniel McAuley, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Kathryn Rowan, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Steve Webb, Ryan Zarychanski, Lewis Campbell, Andrew Forbes, David Gattas, Stephane Heritier, Lisa Higgins, Peter Kruger, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Paul Young, Sean Bagshaw, Nick Daneman, Niall Ferguson, Cheryl Misak, Marlene Santos, Sebastiaan Hullegie, Mathias Pletz, Gernot Rohde, Kathy Rowan, Brian Alexander, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Kelsey Linstrum, Jennifer Vates, Richard Beasley, Robert Fowler, Steve McGloughlin, Susan Morpeth, David Paterson, Bala Venkatesh, Tim Uyeki, Kenneth Baillie, Eamon Duffy, Rob Fowler, Thomas Hills, Katrina Orr, Asad Patanwala, Steve Tong, Mihai Netea, Shilesh Bihari, Marc Carrier, Dean Fergusson, Ewan Goligher, Ghady Haidar, Beverley Hunt, Anand Kumar, Mike Laffan, Patrick Lawless, Sylvain Lother, Peter McCallum, Saskia Middeldopr, Zoe McQuilten, Matthew Neal, John Pasi, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Alexandra Weissman, Neill Adhikari, Matthew Anstey, Emily Brant, Angelique de Man, Francois Lamonagne, Marie-Helene Masse, Andrew Udy, Donald Arnold, Phillipe Begin, Richard Charlewood, Michael Chasse, Mark Coyne, Jamie Cooper, James Daly, Iain Gosbell, Heli Harvala-Simmonds, Tom Hills, Sheila MacLennan, David Menon, John McDyer, Nicole Pridee, David Roberts, Manu Shankar-Hari, Helen Thomas, Alan Tinmouth, Darrell Triulzi, Tim Walsh, Erica Wood, Carolyn Calfee, Cecilia O’Kane, Murali Shyamsundar, Pratik Sinha, Taylor Thompson, Ian Young, Shailesh Bihari, Carol Hodgson, John Laffey, Danny McAuley, Neil Orford, Ary Neto, Michelle Detry, Mark Fitzgerald, Roger Lewis, Anna McGlothlin, Ashish Sanil, Christina Saunders, Lindsay Berry, Elizabeth Lorenzi, Eliza Miller, Vanessa Singh, Claire Zammit, Wilma van Bentum Puijk, Wietske Bouwman, Yara Mangindaan, Lorraine Parker, Svenja Peters, Ilse Rietveld, Kik Raymakers, Radhika Ganpat, Nicole Brillinger, Rene Markgraf, Kate Ainscough, Kathy Brickell, Aisha Anjum, Janis-Best Lane, Alvin Richards-Belle, Michelle Saull, Daisy Wiley, Julian Bion, Jason Connor, Simon Gates, Victoria Manax, Tom van der Poll, John Reynolds, Marloes van Beurden, Evelien Effelaar, Joost Schotsman, Craig Boyd, Cain Harland, Audrey Shearer, Jess Wren, Giles Clermont, William Garrard, Kyle Kalchthaler, Andrew King, Daniel Ricketts, Salim Malakoutis, Oscar Marroquin, Edvin Music, Kevin Quinn, Heidi Cate, Karen Pearson, Joanne Collins, Jane Hanson, Penny Williams, Shane Jackson, Adeeba Asghar, Sarah Dyas, Mihaela Sutu, Sheenagh Murphy, Dawn Williamson, Nhlanhla Mguni, Alison Potter, David Porter, Jayne Goodwin, Clare Rook, Susie Harrison, Hannah Williams, Hilary Campbell, Kaatje Lomme, James Williamson, Jonathan Sheffield, Willian van’t Hoff, Phobe McCracken, Meredith Young, Jasmin Board, Emma Mart, Cameron Knott, Julie Smith, Catherine Boschert, Julia Affleck, Mahesh Ramanan, Ramsy D’Souza, Kelsey Pateman, Arif Shakih, Winston Cheung, Mark Kol, Helen Wong, Asim Shah, Atul Wagh, Joanne Simpson, Graeme Duke, Peter Chan, Brittney Cartner, Stephanie Hunter, Russell Laver, Tapaswi Shrestha, Adrian Regli, Annamaria Pellicano, James McCullough, Mandy Tallott, Nikhil Kumar, Rakshit Panwar, Gail Brinkerhoff, Cassandra Koppen, Federica Cazzola, Matthew Brain, Sarah Mineall, Roy Fischer, Vishwanath Biradar, Natalie Soar, Hayden White, Kristen Estensen, Lynette Morrison, Joanne Smith, Melanie Cooper, Monash Health, Yahya Shehabi, Wisam Al-Bassam, Amanda Hulley, Christina Whitehead, Julie Lowrey, Rebecca Gresha, James Walsham, Jason Meyer, Meg Harward, Ellen Venz, Patricia Williams, Catherine Kurenda, Kirsy Smith, Margaret Smith, Rebecca Garcia, Deborah Barge, Deborah Byrne, Kathleen Byrne, Alana Driscoll, Louise Fortune, Pierre Janin, Elizabeth Yarad, Naomi Hammond, Frances Bass, Angela Ashelford, Sharon Waterson, Steve Wedd, Robert McNamara, Heidi Buhr, Jennifer Coles, Sacha Schweikert, Bradley Wibrow, Rashmi Rauniyar, Erina Myers, Ed Fysh, Ashlish Dawda, Bhaumik Mevavala, Ed Litton, Janet Ferrier, Priya Nair, Hergen Buscher, Claire Reynolds, John Santamaria, Leanne Barbazza, Jennifer Homes, Roger Smith, Lauren Murray, Jane Brailsford, Loretta Forbes, Teena Maguire, Vasanth Mariappa, Judith Smith, Scott Simpson, Matthew Maiden, Allsion Bone, Michelle Horton, Tania Salerno, Martin Sterba, Wenli Geng, Pieter Depuydt, Jan De Waele, Liesbet De Bus, Jan Fierens, Stephanie Bracke, Brenda Reeve, William Dechert, Michaël Chassé, François Martin Carrier, Dounia Boumahni, Fatna Benettaib, Ali Ghamraoui, David Bellemare, Ève Cloutier, Charles Francoeur, François Lamontagne, Frédérick D’Aragon, Elaine Carbonneau, Julie Leblond, Gloria Vazquez-Grande, Nicole Marten, Maggie Wilson, Martin Albert, Karim Serri, Alexandros Cavayas, Mathilde Duplaix, Virginie Williams, Bram Rochwerg, Tim Karachi, Simon Oczkowski, John Centofanti, Tina Millen, Erick Duan, Jennifer Tsang, Lisa Patterson, Shane English, Irene Watpool, Rebecca Porteous, Sydney Miezitis, Lauralyn McIntyre, Laurent Brochard, Karen Burns, Gyan Sandhu, Imrana Khalid, Alexandra Binnie, Elizabeth Powell, Alexandra McMillan, Tracy Luk, Noah Aref, Zdravko Andric, Sabina Cviljevic, Renata Đimoti, Marija Zapalac, Gordan Mirković, Bruno Baršić, Marko Kutleša, Viktor Kotarski, Ana Vujaklija Brajković, Jakša Babel, Helena Sever, Lidija Dragija, Ira Kušan, Suvi Vaara, Leena Pettilä, Jonna Heinonen, Anne Kuitunen, Sari Karlsson, Annukka Vahtera, Heikki Kiiski, Sanna Ristimäki, Amine Azaiz, Cyril Charron, Mathieu Godement, Guillaume Geri, Antoine Vieillard-Baron, Franck Pourcine, Mehran Monchi, David Luis, Romain Mercier, Anne Sagnier, Nathalie Verrier, Cecile Caplin, Shidasp Siami, Christelle Aparicio, Sarah Vautier, Asma Jeblaoui, Muriel Fartoukh, Laura Courtin, Vincent Labbe, Cécile Leparco, Grégoire Muller, Mai-Anh Nay, Toufik Kamel, Dalila Benzekri, Sophie Jacquier, Emmanuelle Mercier, Delphine Chartier, Charlotte Salmon, PierreFrançois Dequin, Francis Schneider, Guillaume Morel, Sylvie L’Hotellier, Julio Badie, Fernando Daniel Berdaguer, Sylvain Malfroy, Chaouki Mezher, Charlotte Bourgoin, Bruno Megarbane, Sebastian Voicu, Nicolas Deye, Isabelle Malissin, Laetitia Sutterlin, Christophe Guitton, Cédric Darreau, Mickaël Landais, Nicolas Chudeau, Alain Robert, Pierre Moine, Nicholas Heming, Virginie Maxime, Isabelle Bossard, Tiphaine Barbarin Nicholier, Gwenhael Colin, Vanessa Zinzoni, Natacham Maquigneau, André Finn, Gabriele Kreß, Uwe Hoff, Carl Friedrich Hinrichs, Jens Nee, Mathias Pletz, Stefan Hagel, Juliane Ankert, Steffi Kolanos, Frank Bloos, Sirak Petros, Bastian Pasieka, Kevin Kunz, Peter Appelt, Bianka Schütze, Stefan Kluge, Axel Nierhaus, Dominik Jarczak, Kevin Roedl, Dirk Weismann, Anna Frey, Vivantes Klinikum Neukölln, Lorenz Reill, Michael Distler, Astrid Maselli, János Bélteczki, István Magyar, Ágnes Fazekas, Sándor Kovács, Viktória Szőke, Gábor Szigligeti, János Leszkoven, Daniel Collins, Patrick Breen, Stephen Frohlich, Ruth Whelan, Bairbre McNicholas, Michael Scully, Siobhan Casey, Maeve Kernan, Peter Doran, Michael O’Dywer, Michelle Smyth, Leanne Hayes, Oscar Hoiting, Marco Peters, Els Rengers, Mirjam Evers, Anton Prinssen, Jeroen Bosch Ziekenhuis, Koen Simons, Wim Rozendaal, F Polderman, P de Jager, M Moviat, A Paling, A Salet, Emma Rademaker, Anna Linda Peters, E de Jonge, J Wigbers, E Guilder, M Butler, Keri-Anne Cowdrey, Lynette Newby, Yan Chen, Catherine Simmonds, Rachael McConnochie, Jay Ritzema Carter, Seton Henderson, Kym Van Der Heyden, Jan Mehrtens, Tony Williams, Alex Kazemi, Rima Song, Vivian Lai, Dinu Girijadevi, Robert Everitt, Robert Russell, Danielle Hacking, Ulrike Buehner, Erin Williams, Troy Browne, Kate Grimwade, Jennifer Goodson, Owen Keet, Owen Callender, Robert Martynoga, Kara Trask, Amelia Butler, Livia Schischka, Chelsea Young, Eden Lesona, Shaanti Olatunji, Yvonne Robertson, Nuno José, Teodoro Amaro dos Santos Catorze, Tiago Nuno Alfaro de Lima Pereira, Lucilia Maria Neves Pessoa, Ricardo Manuel Castro Ferreira, Joana Margarida Pereira Sousa Bastos, Simin Aysel Florescu, Delia Stanciu, Miahela Florentina Zaharia, Alma Gabriela Kosa, Daniel Codreanu, Yaseen Marabi, Eman Al Qasim, Mohamned Moneer Hagazy, Lolowa Al Swaidan, Hatim Arishi, Rosana Muñoz-Bermúdez, Judith Marin-Corral, Anna Salazar Degracia, Francisco Parrilla Gómez, Maria Isabel Mateo López, Jorge Rodriguez Fernandez, Sheila Cárcel Fernández, Rosario Carmona Flores, Rafael León López, Carmen de la Fuente Martos, Angela Allan, Petra Polgarova, Neda Farahi, Stephen McWilliam, Daniel Hawcutt, Laura Rad, Laura O’Malley, Jennifer Whitbread, Olivia Kelsall, Laura Wild, Jessica Thrush, Hannah Wood, Karen Austin, Adrian Donnelly, Martin Kelly, Sinéad O’Kane, Declan McClintock, Majella Warnock, Paul Johnston, Linda Jude Gallagher, Clare Mc Goldrick, Moyra Mc Master, Anna Strzelecka, Rajeev Jha, Michael Kalogirou, Christine Ellis, Vinodh Krishnamurthy, Vashish Deelchand, Jon Silversides, Peter McGuigan, Kathryn Ward, Aisling O’Neill, Stephanie Finn, Barbara Phillips, Dee Mullan, Laura Oritz-Ruiz de Gordoa, Matthew Thomas, Katie Sweet, Lisa Grimmer, Rebekah Johnson, Jez Pinnell, Matt Robinson, Lisa Gledhill, Tracy Wood, Matt Morgan, Jade Cole, Helen Hill, Michelle Davies, David Antcliffe, Maie Templeton, Roceld Rojo, Phoebe Coghlan, Joanna Smee, Euan Mackay, Jon Cort, Amanda Whileman, Thomas Spencer, Nick Spittle, Vidya Kasipandian, Amit Patel, Suzanne Allibone, Roman Mary Genetu, Mohamed Ramali, Alison Ghosh, Peter Bamford, Emily London, Kathryn Cawley, Maria Faulkner, Helen Jeffrey, Tim Smith, Chris Brewer, Jane Gregory, James Limb, Amanda Cowton, Julie O’Brien, Nikitas Nikitas, Colin Wells, Liana Lankester, Mark Pulletz, Patricia Williams, Jenny Birch, Sophie Wiseman, Sarah Horton, Ana Alegria, Salah Turki, Tarek Elsefi, Nikki Crisp, Louise Allen, Iain McCullagh, Philip Robinson, Carole Hays, Maite Babio-Galan, Hannah Stevenson, Divya Khare, Meredith Pinder, Selvin Selvamoni, Amitha Gopinath, Richard Pugh, Daniel Menzies, Callum Mackay, Elizabeth Allan, Gwyneth Davies, Kathryn Puxty, Claire McCue, Susanne Cathcart, Naomi Hickey, Jane Ireland, Hakeem Yusuff, Graziella Isgro, Chris Brightling, Michelle Bourne, Michelle Craner, Malcolm Watters, Rachel Prout, Louisa Davies, Suzannah Pegler, Lynsey Kyeremeh, Gill Arbane, Karen Wilson, Linda Gomm, Federica 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Lynn Wren, Felicity Willams, Richard Innes, Patricia Doble, Joanne Hutter, Charmaine Shovelton, Benjamin Plumb, Tamas Szakmany, Vincent Hamlyn, Nancy Hawkins, Sarah Lewis, Amanda Dell, Shameer Gopal, Saibal Ganguly, Andrew Smallwood, Nichola Harris, Stella Metherell, Juan Martin Lazaro, Tabitha Newman, Simon Fletcher, Jurgens Nortje, Deirdre Fottrell-Gould, Georgina Randell, Mohsin Zaman, Einas Elmahi, Andrea Jones, Kathryn Hall, Gary Mills, Kim Ryalls, Helen Bowler, Jas Sall, Richard Bourne, Zoe Borrill, Tracey Duncan, Thomas Lamb, Joanne Shaw, Claire Fox, Jeronimo Moreno Cuesta, Kugan Xavier, Dharam Purohit, Munzir Elhassan, Dhanalakshmi Bakthavatsalam, Matthew Rowland, Paula Hutton, Archana Bashyal, Neil Davidson, Clare Hird, Manish Chhablani, Gunjan Phalod, Amy Kirkby, Simon Archer, Kimberley Netherton, Henrik Reschreiter, Julie Camsooksai, Sarah Patch, Sarah Jenkins, David Pogson, Steve Rose, Zoe Daly, Lutece Brimfield, Helen Claridge, Dhruv Parekh, Colin Bergin, Michelle Bates, Joanne Dasgin, Christopher McGhee, Malcolm Sim, Sophie Kennedy Hay, Steven Henderson, Mandeep-Kaur Phull, Abbas Zaidi, Tatiana Pogreban, Lace Paulyn Rosaroso, Daniel Harvey, Benjamin Lowe, Megan Meredith, Lucy Ryan, Anil Hormis, Rachel Walker, Dawn Collier, Sarah Kimpton, Susan Oakley, Kevin Rooney, Natalie Rodden, Emma Hughes, Nicola Thomson, Deborah McGlynn, Andrew Walden, Nicola Jacques, Holly Coles, Emma Tilney, Emma Vowell, Martin Schuster-Bruce, Sally Pitts, Rebecca Miln, Laura Purandare, Luke Vamplew, Michael Spivey, Sarah Bean, Karen Burt, Lorraine Moore, Christopher Day, Charly Gibson, Elizabeth Gordon, Letizia Zitter, Samantha Keenan, Evelyn Baker, Shiney Cherian, Sean Cutler, Anna Roynon-Reed, Kate Harrington, Ajay Raithatha, Kris Bauchmuller, Norfaizan Ahmad, Irina Grecu, Dawn Trodd, Jane Martin, Caroline Wrey Brown, Ana-Marie Arias, Thomas Craven, David Hope, Jo Singleton, Sarah Clark, Nicola Rae, Ingeborg Welters, David Oliver Hamilton, Karen Williams, Victoria Waugh, David Shaw, Zudin Puthucheary, Timothy Martin, Filipa Santos, Ruzena Uddin, Alastair Somerville, Kate Colette Tatham, Shaman Jhanji, Ethel Black, Arnold Dela Rosa, Ryan Howle, Redmond Tully, Andrew Drummond, Joy Dearden, Jennifer Philbin, Sheila Munt, Alain Vuylsteke, Charles Chan, Saji Victor, Ramprasad Matsa, Minerva Gellamucho, Ben Creagh-Brown, Joe Tooley, Laura Montague, Fiona De Beaux, Laetitia Bullman, Ian Kersiake, Carrie Demetriou, Sarah Mitchard, Lidia Ramos, Katie White, Phil Donnison, Maggie Johns, Ruth Casey, Lehentha Mattocks, Sarah Salisbury, Paul Dark, Andrew Claxton, Danielle McLachlan, Kathryn Slevin, Stephanie Lee, Jonathan Hulme, Sibet Joseph, Fiona Kinney, Ho Jan Senya, Aneta Oborska, Abdul Kayani, Bernard Hadebe, Rajalakshmi Orath Prabakaran, Lesley Nichols, Matt Thomas, Ruth Worner, Beverley Faulkner, Emma Gendall, Kati Hayes, Colin Hamilton-Davies, Carmen Chan, Celina Mfuko, Hakam Abbass, Vineela Mandadapu, Susannah Leaver, Daniel Forton, Kamal Patel, Elankumaran Paramasivam, Matthew Powell, Richard Gould, Elizabeth Wilby, Clare Howcroft, Dorota Banach, Ziortza Fernández de Pinedo Artaraz, Leilani Cabreros, Ian White, Maria Croft, Nicky Holland, Rita Pereira, Ahmed Zaki, David Johnson, Matthew Jackson, Hywel Garrard, Vera Juhaz, Alistair Roy, Anthony Rostron, Lindsey Woods, Sarah Cornell, Suresh Pillai, Rachel Harford, Tabitha Rees, Helen Ivatt, Ajay Sundara Raman, Miriam Davey, Kelvin Lee, Russell Barber, Manish Chablani, Farooq Brohi, Vijay Jagannathan, Michele Clark, Sarah Purvis, Bill Wetherill, Ahilanandan Dushianthan, Rebecca Cusack, Kim de Courcy-Golder, Simon Smith, Susan Jackson, Ben Attwood, Penny Parsons, Valerie Page, Xiao Bei Zhao, Deepali Oza, Jonathan Rhodes, Tom Anderson, Sheila Morris, Charlotte Xia Le Tai, Amy Thomas, Alexandra Keen, Stephen Digby, Nicholas Cowley, Laura Wild, David Southern, Harsha Reddy, Andy Campbell, Claire Watkins, Sara Smuts, Omar Touma, Nicky Barnes, Peter Alexander, Tim Felton, Susan Ferguson, Katharine Sellers, Joanne Bradley-Potts, David Yates, Isobel Birkinshaw, Kay Kell, Nicola Marshall, Lisa Carr-Knott, Charlotte Summers, and Mégarbane, Bruno

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Writing Committee for the REMAP-CAP Investigators, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, General & Internal Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 11 Medical and Health Sciences
Abstract

Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Published
2020
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