Bruno Levy1,2,3, Nicolas Girerd4,5, Julien Amour6, Emmanuel Besnier7,8, Nicolas Nesseler9,10, Julie Helms11, Clément Delmas12, Romain Sonneville13, Catherine Guidon14, Bertrand Rozec15,16, Helène David17,18, David Bougon19, Oussama Chaouch20, Oulehri Walid21, Dupont Hervé22, Nicolas Belin23, Lucie Gaide-Chevronnay24, Patrick Rossignol19, Antoine Kimmoun1, Kevin Duarte25, Arthur S Slutsky26,27, Daniel Brodie28, Jean-Luc Fellahi29,30, Alexandre Ouattara31,32, Alain Combes33,34. 1. Médecine Intensive et Réanimation, CHRU Nancy, Pôle Cardio-Médico-Chirurgical, Vandoeuvre-les-Nancy, France. 2. INSERM U1116, Faculté de Médecine, Vandoeuvre-les-Nancy, France. 3. Université de Lorraine, Nancy, France. 4. Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy, Institut Lorrain du Coeur et des Vaisseaux, Nancy, Frances. 5. INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, Nancy, France. 6. Institut de Perfusion, de Réanimation et d'Anesthésie de Chirurgie Cardiaque Paris Sud, Hôpital Privé Jacques Cartier, Massy, France. 7. Department of Anaesthesiology and Critical Care, Rouen University Hospital, Rouen, France. 8. Normandie University, UNIROUEN, INSERM U1096, EnVi, Rouen, France. 9. Department of Anesthesia and Critical Care, Pontchaillou, University Hospital of Rennes, Rennes, France. 10. University Rennes, CHU de Rennes, Inra, INSERM, Institut NUMECAN - UMR_A 1341, UMR_S 1241, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, France. 11. Université de Strasbourg, Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Strasbourg, France. 12. Intensive Cardiac Care Unit, Rangueil University Hospital, Toulouse, France. 13. AP-HP, Bichat Hospital, Medical and infectious diseases ICU, Paris, France. 14. Pôle Anesthésie-Réanimation, Marseille, France. 15. Service d'Anesthésie-Réanimation, Hôpital G&R Laennec CHU de Nantes, Nantes, France. 16. L'institut du Thorax INSERM, CNRS, CHU Nantes, UNIV Nantes, Nantes, France. 17. Department of Anesthesiology and Critical Care Medicine, Arnaud de Villeneuve Hospital, CHU Montpellier, Montpellier, France. 18. Montpellier University, INSERM, CNRS, PhyMedExp, Montpellier, France. 19. Service de Réanimation, Centre Hospitalier Annecy, Genevois, France. 20. Hôpital Européen Georges Pompidou, AP-HP, Department of Anesthesiology and Critical Care Medicine, Université Paris Descartes, Paris, France. 21. Service d'Anesthésie-Réanimation et Médecine péri-Opératoire, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 22. Réanimation Médico-Chirurgicale Cardio-Thoracique, Vasculaire et Respiratoire, CHU Amiens Picardie, Amiens, France. 23. Service de Réanimation Médicale, CHU Besançon, Besançon, France. 24. Unité de Réanimation Cardiovasculaire et Thoracique, Pôle Anesthésie Réanimation, CHU de Grenoble Alpes, Grenoble, France. 25. Université de Lorraine, Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy, Institut Lorrain du Coeur et des Vaisseaux, Nancy, France. 26. Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada. 27. Department of Medicine, Surgery, and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. 28. Department of Medicine, College of Physicians and Surgeons, Columbia University, and the Center for Acute Respiratory Failure, New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York. 29. Service d'Anesthésie-Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 30. Laboratoire CarMeN, INSERM 1060, Université Lyon 1 Claude Bernard, Lyon, France. 31. CHU Bordeaux, Department of Anaesthesia and Critical Care, Magellan Medico-Surgical Centre, Bordeaux, France. 32. University Bordeaux, INSERM, UMR 1034, Biology of Cardiovascular Diseases, Pessac, France. 33. Sorbonne Université, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. 34. Service de Médecine Intensive-Réanimation, Institut de Cardiologie, APHP Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France.
Abstract
IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To 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 PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The 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. RESULTS: Among 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 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). 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 RELEVANCE: In 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.
IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To 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 PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The 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. RESULTS: Among 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 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). 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 RELEVANCE: In 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.
Authors: Niklas Nielsen; Jørn Wetterslev; Tobias Cronberg; David Erlinge; Yvan Gasche; Christian Hassager; Janneke Horn; Jan Hovdenes; Jesper Kjaergaard; Michael Kuiper; Tommaso Pellis; Pascal Stammet; Michael Wanscher; Matt P Wise; Anders Åneman; Nawaf Al-Subaie; Søren Boesgaard; John Bro-Jeppesen; Iole Brunetti; Jan Frederik Bugge; Christopher D Hingston; Nicole P Juffermans; Matty Koopmans; Lars Køber; Jørund Langørgen; Gisela Lilja; Jacob Eifer Møller; Malin Rundgren; Christian Rylander; Ondrej Smid; Christophe Werer; Per Winkel; Hans Friberg Journal: N Engl J Med Date: 2013-11-17 Impact factor: 91.245
Authors: Tanveer Rab; Supawat Ratanapo; Karl B Kern; Mir Babar Basir; Michael McDaniel; Perwaiz Meraj; Spencer B King; William O'Neill Journal: J Am Coll Cardiol Date: 2018-10-16 Impact factor: 24.094
Authors: Roland Prondzinsky; Susanne Unverzagt; Henning Lemm; Nikolas-Arne Wegener; Axel Schlitt; Konstantin M Heinroth; Sebastian Dietz; Ute Buerke; Patrick Kellner; Harald Loppnow; Martin G Fiedler; Joachim Thiery; Karl Werdan; Michael Buerke Journal: Clin Res Cardiol Date: 2012-01-03 Impact factor: 5.460
Authors: Pedro A Villablanca; Gaurav Rao; David F Briceno; Marissa Lombardo; Harish Ramakrishna; Anna Bortnick; Mario García; Mark Menegus; Daniel Sims; Mohammed Makkiya; Farouk Mookadam Journal: Heart Date: 2016-02-10 Impact factor: 5.994
Authors: Jasmeet Soar; Katherine M Berg; Lars W Andersen; Bernd W Böttiger; Sofia Cacciola; Clifton W Callaway; Keith Couper; Tobias Cronberg; Sonia D'Arrigo; Charles D Deakin; Michael W Donnino; Ian R Drennan; Asger Granfeldt; Cornelia W E Hoedemaekers; Mathias J Holmberg; Cindy H Hsu; Marlijn Kamps; Szymon Musiol; Kevin J Nation; Robert W Neumar; Tonia Nicholson; Brian J O'Neil; Quentin Otto; Edison Ferreira de Paiva; Michael J A Parr; Joshua C Reynolds; Claudio Sandroni; Barnaby R Scholefield; Markus B Skrifvars; Tzong-Luen Wang; Wolfgang A Wetsch; Joyce Yeung; Peter T Morley; Laurie J Morrison; Michelle Welsford; Mary Fran Hazinski; Jerry P Nolan Journal: Resuscitation Date: 2020-10-21 Impact factor: 5.262