1. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial
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Bruno, Levy, Nicolas, Girerd, Julien, Amour, Emmanuel, Besnier, Nicolas, Nesseler, Julie, Helms, Clément, Delmas, Romain, Sonneville, Catherine, Guidon, Bertrand, Rozec, Helène, David, David, Bougon, Oussama, Chaouch, Oulehri, Walid, Dupont, Hervé, Nicolas, Belin, Lucie, Gaide-Chevronnay, Patrick, Rossignol, Antoine, Kimmoun, Kevin, Duarte, Arthur S, Slutsky, Daniel, Brodie, Jean-Luc, Fellahi, Alexandre, Ouattara, Alain, Combes, Michel, Kindo, 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), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Privé Jacques Cartier [Massy], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Columbia University [New York], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], 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), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The trial was sponsored and conducted by the Direction de la Recherche Clinique, CHU Nancy, with a grant from the French Ministry of Health., HYPO-ECMO Trial Group and the International ECMO Network (ECMONet): Mathieu Mattei MD, Carine Thivillier MD, Thomas Auchet MD, Pierrre Perez MD, Caroline Fritz MD, Pablo Maureira MD, PhD, Maxime Hubert MD, Yihua Liu MD, PhD, Ferhat Meziani MD, PhD, Hamid Merdji MD, Alexandra Monnier MD, Raphaël Clere-Jehl MD, Ania Nieszkowska MD, Marc Pineton MD, Juliette Chommeloux MD, Guillaume Hékimian MD, Guillaume Lebreton MD, Astrid Quessard MD, Julien Imbault MD, Alain Rémy MD, Mathieu Pernot MD, Pierre Joseph MD, Giovanni Scollo MD, Matteo Pozzi MD, PhD, Étienne Escudier MD, Michel Muller MD, Didier Dorez MD, Michel Sirodot MD, Fabien Doguet MD, Vincent Scherrer MD, Chadi Aludaat MD, Michael Bernasinski MD, Elie Zogheib MD, PhD, Thierry Caus MD, PhD, Philippe Bizouarn MD, PhD, Mickael Vourc'h MD, PhD, Jean-Christian Roussel MD, PhD, Thomas Senage MD, PhD, Erwan Flecher MD, PhD, Jean-Philippe Verhoye MD, PhD, Antoine Roisne MD, Sébastien Biedermann MD, Fanny Vardon-Bounes MD, PhD, Laure Crognier MD, Jean Porterie MD, Pascal Colson MD, PhD, Philippe Gaudard MD, PhD, Philippe Rouviere MD, Lila Bouadma MD, PhD, Fabrice Sinnah MD, PhD, Patrick Nataf MD, PhD, Marylou Para MD, Pauline Dureau MD, Nima Djavidi MD, Adrien Bouglé MD, PhD, Pascal Leprince MD, PhD, Géraldine Dessertaine MD, Michel Durand MD, Pierre Albaladejo MD, Cecile Martin MD, François Belon MD, Gael Piton MD, PhD, Hadrien Winiszewski MD, Andrea Perroti MD, David Tonon MD, Bernard Cholley MD, PhD, Diane Zlotnik MD, Paul Achouh MD, PhD, Hélène Nougue MD, PhD, Olivier Collange MD, PhD, Paul Michel Mertes MD, PhD, Michel Kindo MD, PhD, and Jonchère, Laurent
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Male ,Time Factors ,[SDV]Life Sciences [q-bio] ,Shock, Cardiogenic ,Hemorrhage ,General Medicine ,Middle Aged ,Respiration, Artificial ,Body Temperature ,[SDV] Life Sciences [q-bio] ,Renal Replacement Therapy ,Stroke ,Extracorporeal Membrane Oxygenation ,Hypothermia, Induced ,Sepsis ,Confidence Intervals ,Intubation, Intratracheal ,Heart Transplantation ,Humans ,Female ,France ,Heart-Assist Devices ,Erythrocyte Transfusion ,Original Investigation - Abstract
ImportanceThe optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.ObjectiveTo determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Design, Setting, and ParticipantsRandomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for InterventionsEarly moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166).Main Outcomes and MeasuresThe primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO.ResultsAmong the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, −8.3% [95% CI, −16.3% to −0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.57 (95% CI, 0.36 to 0.90; P = .02) for the moderate hypothermia group compared with the normothermia group and the risk difference was −12.7% (95% CI, −22.3% to −3.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group.Conclusions and RelevanceIn this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive.Trial RegistrationClinicalTrials.gov Identifier: NCT02754193
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- 2022
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