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1. Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment

Author

Jean-Michel Constantin, Axelle Van Lander, Laurent Argaud, Jean-Christophe Richard, Bertrand Souweine, Céline Lambert, Renaud Guérin, Alexandre Fratani, Jean Dellamonica, Russell Chabanne, Jeremy Bourenne, Kada Klouche, Margot Smirdec, Nicolas Terzi, Pierre Asfar, Jean-Pierre Quenot, A Lautrette, Cécile Aubron, Philippe Verdier, Virginie Guastella, Pierre-Marie Bertrand, Anne Medard, Jean-Marc Doise, Nathanael Eisenmann, Samir Jaber, Bruno Pereira, Jean Reignier, Jean-Philippe Rigaud, Mercé Jourdain, Julie Delmas, CHU Clermont-Ferrand, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Anesthésie et de Soins Intensifs [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôtel-Dieu de Nantes, Centre hospitalier de Dieppe, Centre Hospitalier Chalon-sur-Saône William Morey, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Rodez, Centre Hospitalier de Cannes, Hôpital de Montluçon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Grenoble, Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), 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)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), 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), 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)-Université Claude Bernard Lyon 1 (UCBL), and MORNET, Dominique

Subjects
Adult, Male, medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], Relative standard deviation, Decision Making, Intensivist, Critical Care and Intensive Care Medicine, Advance directives, 03 medical and health sciences, 0302 clinical medicine, Qualitative analysis, Life sustaining treatment, Physicians, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Trial registration, Fear of pain, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, Middle Aged, Decisions to forgo life-sustaining treatment, [SDV] Life Sciences [q-bio], 030228 respiratory system, Withholding Treatment, Emergency medicine, ICU, Female, France, business
Abstract

Background There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. Methods We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients’ characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). Results A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. Conclusions ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist’s decision took priority. Further research is needed to improve the matching of the physicians’ decision with the patient’s wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530.

Published
2020
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2. Early Changes Over Time in the Radiographic Assessment of Lung Edema Score Are Associated With Survival in ARDS

Author

Yoann Launey, Olivier Langeron, Claire Roger, Marion Monnin, M. Cisse, Julie A. Bastarache, Matthieu Jabaudon, Audrey De Jong, Emmanuel Futier, Jean-Pierre Quenot, Philippe Seguin, Mathieu Calypso, Matthieu Conseil, Benoit Veber, Garry Duclos, François Legay, Serge Molliex, Raiko Blondonnet, Julie Carr, Pablo Massanet, Mathilde Barbaz, Fabien Grelon, Jean-Etienne Bazin, Caroline Boutin, Céline Lambert, Emmanuelle Hammad, Jules Audard, Mona Assefi, Anne-Charlotte Tellier, Thomas Godet, Alexandre Lautrette, Hadanou Nanadougmar, Bernard Cosserant, Claire Dahyot-Fizelier, Charlotte Arbelot, Hervé Quintard, Jean-Yves Lefrant, Raphael Cinotti, Achile Sossou, Gerald Chanques, Martine Ferrandière, Thomas Lebouvrier, Marc Leone, Marinne Le Core, Renaud Guérin, Frank Petitas, Thomas Crozon, Edouard Lemarche, Saber Barbar, Camille Verlhac, Jean-Christophe Orban, Sigismond Lasocki, Hervé Dupont, Julien Clauzel, Jean-Michel Constantin, Fouad Belafia, Pascal Andreu, Thomas Rimmelé, Carole Ichai, Russell Chabanne, Karim Asehnoune, Jerome Morel, Antoine Roquilly, Nathanael Eisenmann, Pierre-Marie Bertrand, Samir Jaber, Auguste Dargent, Bertrand Souweine, Lorraine B. Ware, Laurent Muller, Bruno Pereira, Benjamin Cohen, Sophie Cayot, and Laurent Zieleskiewicz

Subjects
Pulmonary and Respiratory Medicine, Male, ARDS, Organ Dysfunction Scores, Pulmonary Edema, Critical Care and Intensive Care Medicine, Severity of Illness Index, survival, RALE, Radiographic Assessment of Lung Edema, 03 medical and health sciences, 0302 clinical medicine, radiographic score, medicine, Clinical endpoint, Image Processing, Computer-Assisted, Humans, 030212 general & internal medicine, Simplified Acute Physiology Score, Lung, Survival analysis, sRAGE, soluble receptor for advanced glycation end-products, Proportional Hazards Models, FACTT, Fluid and Catheter Treatment Trial, Respiratory Distress Syndrome, business.industry, Surrogate endpoint, Hazard ratio, treatable trait, LIVE, Lung Imaging for Ventilation sEtting in ARDS, Middle Aged, Pulmonary edema, medicine.disease, Prognosis, SAPS, Simplified Acute Physiology Score, Survival Analysis, HR, hazard ratio, 3. Good health, CHU, Centre Hospitalier Universitaire, Clinical trial, Radiography, Outcome and Process Assessment, Health Care, 030228 respiratory system, Anesthesia, Critical Care: Original Research, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Background The Radiographic Assessment of Lung Edema (RALE) score is associated with the severity of ARDS, and treatments targeted at reducing pulmonary edema such as conservative fluid management cause a reduction in RALE score over time. Research Question Are early changes in RALE score over time associated with survival in patients with ARDS? Study Design and Methods Data from patients enrolled in three centers in the Lung Imaging for Ventilation sEtting in ARDS (LIVE) trial with available chest radiographs at baseline (day 0) and days 2 or 3 were used. The RALE was scored by two independent reviewers. The primary end point was death by day 90, considering RALE score both at baseline and as a time-varying covariate in a marginal Cox survival model. Results RALE was scored from 135, 64, and 88 radiographs on days 0, 2, and 3, respectively. Both baseline RALE (hazard ratio [HR] for each one-point increment, 1.04; 95% CI, 1.01-1.08; P = .006) and the change in RALE over time (HR for each one-point decrease per unit of time, 0.99; 95% CI, 0.99-0.99; P = .03) were associated with death by day 90, even after adjustment for age, sex, BMI, Simplified Acute Physiology Score II, vasopressor use, and total volume of fluids received since study entry. Interpretation The change in RALE during the first days after ARDS onset is independently associated with survival and may be useful as a surrogate end point in future clinical trials of new therapeutics in ARDS.

Published
2020

3. Driving pressure and acute respiratory distress syndrome in critically ill patients

Author

Pauline Berthelin, Nathanael Eisenmann, Bertrand Souweine, Damien Bouvier, Thibaut Pranal, Sophie Cayot, Bruno Pereira, Jean-Michel Constantin, Raiko Blondonnet, Matthieu Jabaudon, Corinne Belville, Vincent Sapin, Alexandre Lautrette, Thierry Gillart, Russell Chabanne, Loïc Blanchon, Thomas Godet, Elodie Joubert, and Laurence Roszyk

Subjects
Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, education.field_of_study, ARDS, business.industry, medicine.medical_treatment, Population, Odds ratio, Emergency department, medicine.disease, Intensive care unit, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, law, Internal medicine, medicine, 030212 general & internal medicine, Risk factor, business, education, Tidal volume
Abstract

Background and objective Elevated driving pressure (ΔP) may be associated with increased risk of acute respiratory distress syndrome (ARDS) in patients admitted via the emergency department and with post-operative pulmonary complications in surgical patients. This study investigated the association of higher ΔP with the onset of ARDS in a high-risk, intensive care unit (ICU) population. Methods This is a secondary analysis of a prospective multicentre observational study. Data for this ancillary study were obtained from intubated adult patients with at least one ARDS risk factor upon ICU admission enrolled in a previous multicentre observational study. Patients were followed up for the development of ARDS within 7 days (primary outcome). Univariate and multivariate analyses tested the association between ΔP (measured at ICU admission (baseline) or 24 h later (day 1)) and the development of ARDS. Results A total of 221 patients were included in this study, among whom 34 (15%) developed ARDS within 7 days. These patients had higher baseline ΔP than those who did not (mean ± SD: 12.5 ± 3.1 vs 9.8 ± 3.4 cm H2 O, respectively, P = 0.0001). The association between baseline ΔP and the risk of developing ARDS was robust to adjustment for baseline tidal volume, positive-end expiratory pressure, illness severity, serum lactate and sepsis, pneumonia, severe trauma and shock as primary ARDS risk factors (odds ratio: 1.20; 95% CI: 1.03-1.41; P = 0.02). The same results were found with day 1 ΔP. Conclusion Among at-risk ICU patients, higher ΔP may identify those who are more likely to develop ARDS.

Published
2018
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4. Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements

Author

Loic Dopeux, Christelle Simon, Gaëtan Plantefève, Konstantinos Bachoumas, Bertrand Souweine, Roland De Varax, Thibault Duburcq, Julien Bohé, Francis Schneider, Jean-Baptiste Lascarrou, Alexandre Herbland, Pascale Roques, Marcel Benedit, Delphine Bregeaud, Matthieu Jabaudon, Marie-Hélène Hausermann, Aurélie Godard, Russell Chabanne, Samuel Groyer, Albrice Levrat, Frédérique Ganster, Christophe Leroy, Muriel Fartoukh, Laura Frederici, Benoit Painvin, Stephane Rouleau, Ahmed-Saïd Laggoune, Benjamin Rieu, Edouard Soum, Jean Morin, Paul Rooze, Jean-Charles Chakarian, Aurélie Joret, Hervé Dupont, Stéphanie Gelinotte, Vlad Botoc, Nathanael Eisenmann, Jean Reignier, Aurélie Le Thuaut, Toufik Kamel, Timothée Trampont, Cédric Bruel, CH de Saint-Malo [Broussais], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Victor Dupouy, Hôpital Saint-Louis de La Rochelle (CH La Rochelle), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier de Versailles André Mignot (CHV), Pôle de Médecine Périopératoire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Les Hôpitaux Universitaires de Strasbourg (HUS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service de réanimation polyvalente, Groupe Hospitalier Paris Saint-Joseph (hpsj), Medical and Surgical Intensive Care Unit, Groupe Hospitalier Paris Saint Joseph, Paris, Hôtel-Dieu de Nantes, CHU La Roche sur Yon, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Service d'Anesthésie - Réanimation, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Anesthésie Réanimation chirurgicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service des urgences [CHU Limoges], CHU Limoges, Service de Réanimation Médicale Sud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier de Dieppe, 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), CHU Pontchaillou [Rennes], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Reanimation Hôpital de Moulins Yzeure, Moulins, France, Pôle Urgences [CHU Clermont-Ferrand], Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and DESSAIVRE, Louise

Subjects
medicine.medical_specialty, Flail chest, Epidural analgesia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Chest trauma, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, Medicine, Intubation, Mechanical ventilation, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Retrospective cohort study, lcsh:RC86-88.9, medicine.disease, Intensive care unit, [SDV] Life Sciences [q-bio], 030228 respiratory system, SAPS II, Anesthesia, Injury Severity Score, business
Abstract

Background Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV. Study design and methods This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015. Results Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7. Conclusions EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.

Published
2020
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5. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial

Author

Jean-Michel Constantin, Matthieu Jabaudon, Jean-Yves Lefrant, Samir Jaber, Jean-Pierre Quenot, Olivier Langeron, Martine Ferrandière, Fabien Grelon, Philippe Seguin, Carole Ichai, Benoit Veber, Bertrand Souweine, Thomas Uberti, Sigismond Lasocki, François Legay, Marc Leone, Nathanael Eisenmann, Claire Dahyot-Fizelier, Hervé Dupont, Karim Asehnoune, Achille Sossou, Gérald Chanques, Laurent Muller, Jean-Etienne Bazin, Antoine Monsel, Lucile Borao, Jean-Marc Garcier, Jean-Jacques Rouby, Bruno Pereira, Emmanuel Futier, Cayot Sophie, Godet Thomas, Guerin Renaud, Verlac Camille, Chabanne Russel, Cosserant Bernard, Blondonnet Raiko, Lautrette Alexandre, Eisenmann Nathanael, Muller Laurent, Massanet Pablo, Boutin Caroline, Barbar Saber, Roger Claire, Belafia Fouad, Cisse Moussa, Monnin Marion, Conseil Matthieu, Carr Julie, De Jong Audrey, Dargent Auguste, Andreu Pascal, Lebouvrier Thomas, Launey Yoann, Roquilly Antoine, Cinotti Raphael, Tellier Anne-Charlotte, Barbaz Mathilde, Cohen Benjamin, Lemarche Edouard, Bertrand Pierre-Marie, Arberlot Charlotte, Zieleskiewicz Laurent, Hammad Emmanuelle, Duclos Garry, Mathie Calypso, Dupont Herve, Veber Benoit, Orban Jean-Christophe, Quintard Hervé, Rimmele Thomas, Crozon-Clauzel Julien, Le Core Marinne, Grelon Fabien, Assefi Mona, Petitas Frank, Morel Jerome, Molliex Serge, Hadanou Nanadougmar, CHU Clermont-Ferrand, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Le Mans (CH Le Mans), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital St Roch, Département d'anesthésie-Réanimation-Samu, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Edouard Herriot Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU de Saint-Brieuc, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Anesthesiology and Critical Care Medicine, Emile-Roux general hospital, Le Puy-en-Velay, Université de Montpellier (UM), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [APHP], Hopital Général, Le Mans, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Hospital General Saint-Brieuc, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Régional de Lutte Contre le Cancer Jean Perrin, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), University Hospital of Clermont-Ferrand, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Fraction of inspired oxygen, Intensive care, medicine, Prone Position, Tidal Volume, Humans, Single-Blind Method, 030212 general & internal medicine, Prospective Studies, Precision Medicine, Lung, Positive end-expiratory pressure, Tidal volume, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Hazard ratio, Middle Aged, medicine.disease, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Editorial Commentary, Treatment Outcome, 030228 respiratory system, Female, France, business
Abstract

The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589.From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012.Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).

Published
2019
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6. Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study

Author

Nathanael Eisenmann, Yvan Skrzypczak, Thierry Gillart, Thibaut Pranal, Vincent Sapin, Alexandre Lautrette, Bruno Pereira, Julien Pascal, Pauline Berthelin, Russell Chabanne, Matthieu Jabaudon, Laurence Roszyk, Bertrand Souweine, Sophie Cayot, Thomas Godet, Raiko Blondonnet, Loïc Blanchon, Jean-Michel Constantin, Corinne Belville, Jean-Sébastien Faure, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 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)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Biochimie, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Jabaudon, Matthieu

Subjects
Male, ARDS, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Receptor for Advanced Glycation End Products, lcsh:Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, lcsh:Science, Prospective cohort study, MESH: Aged, Respiratory Distress Syndrome, education.field_of_study, Multidisciplinary, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Middle Aged, 3. Good health, Intensive Care Units, medicine.anatomical_structure, Cohort, Female, medicine.medical_specialty, Population, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Intensive care, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Risk factor, education, Aged, Lung, MESH: Humans, business.industry, MESH: Receptor for Advanced Glycation End Products, lcsh:R, 030208 emergency & critical care medicine, medicine.disease, MESH: Male, 030228 respiratory system, MESH: Biomarkers, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Respiratory Distress Syndrome, Adult, lcsh:Q, MESH: Intensive Care Units, business, MESH: Female, Biomarkers
Abstract

International audience; Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS. Acute respiratory distress syndrome (ARDS) still carries a high mortality rate 1,2 , and a major challenge in targeting the prevention and early treatment of ARDS is the inability to accurately predict which patients will develop the syndrome 3-6. The Lung Injury Prediction Score (LIPS) was developed to identify patients at high risk of developing ARDS; however, its positive predictive value is limited (0.14-0.23) 7. To improve prediction, one method may be to combine clinical data with plasma biomarkers that reflect the pathogenesis of ARDS such as angiopoietin-2 (Ang-2), a marker of lung endothelial injury 8. In contrast, the soluble receptor for advanced gly-cation end-products (sRAGE), a marker of lung epithelial injury 9 , may predict ARDS more accurately in selected at-risk patients, e.g. after cardiac surgery 10 , severe trauma 11 , or after major surgery 12. Soluble forms of RAGE (sRAGE) include the extracellular domain of membrane RAGE that is cleaved by proteinases 13 and endogenous secretory RAGE (esRAGE), among other forms produced by alternative splicing 14,15. sRAGE has good diagnostic value for ARDS and is associated with lung injury severity, the degree of lung epithelial injury, impaired alveolar fluid clearance, and prognosis in ARDS 16,17. Although it remains unclear whether esRAGE may be involved in ligand binding or may have any functional effects by itself, esRAGE levels were lower in the plasma and alveolar fluid from patients with ARDS than in mechanically ventilated controls without ARDS in a previous study 18. In addition, and although not yet ready for clinical use, genomic applications could facilitate better prediction

Published
2018
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7. [Jugular venous and arterial concentrations of serum S100B protein in patients with severe head injury]

Author

Pierre Schoeffler, Nathanael Eisenmann, Juliette Bonneau, Damien Bouvier, D. Guelon, Vincent Sapin, Thierry Gillart, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Severe head injury, Adolescent, [SDV]Life Sciences [q-bio], S100 Calcium Binding Protein beta Subunit, Severity of Illness Index, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Craniocerebral Trauma, Humans, Medicine, Glasgow Coma Scale, In patient, Nerve Growth Factors, 030212 general & internal medicine, S100b protein, Aged, Aged, 80 and over, Gynecology, business.industry, Osmolar Concentration, S100 Proteins, Arteries, General Medicine, Middle Aged, Prognosis, 3. Good health, surgical procedures, operative, Case-Control Studies, cardiovascular system, Female, Jugular Veins, business, 030217 neurology & neurosurgery, hormones, hormone substitutes, and hormone antagonists
Abstract

L’evaluation du pronostic des victimes de traumatismes crâniens graves (TCG) est difficile dans la prise en charge de ces patients. Devant la faible sensibilite du score de Glasgow, la proteine S100B semble etre un bon marqueur pronostique. Cependant peu d’etudes sont basees sur des prelevements centraux en jugulaire. L’objectif de notre etude est de comparer l’interet de cinetiques arterielles et jugulaires des concentrations seriques de S100B chez le patient victime d’un TCG. Pour cela, nous avons mene une etude prospective au sein du CHU de Clermont-Ferrand, sur 17 patients orientes en service de reanimation suite a un TCG, dans le but d’evaluer l’interet d’une cinetique de dosages seriques de la proteine S100B en arteriel et en jugulaire au decours de leur prise en charge. Le dosage de la proteine S100B a demontre une concentration mediane de 0,16 μg/L en arteriel et de 0,25 μg/L en jugulaire. Pour l’ensemble des prelevements des 17 patients, la mediane de concentration arterielle en S100B est significativement differente de la mediane de concentration jugulaire. Cette difference significative arterio-jugulaire n’est pas retrouvee dans le sous-groupe des TCG de mauvaise evolution ni dans le sous-groupe des prelevements realises avant les 24 premieres heures post traumatisme. Dans le sous-groupe des TCG de mauvais pronostic, il n’existe pas, contrairement a ce que l’on observe en arteriel, de diminution significative du taux jugulaire de S100B apres les 24 premieres heures post traumatisme. En regard de ces resultats, les dosages en jugulaire semblent donc presenter un meilleur interet pronostique qu’en arteriel.

Published
1970
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