Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial
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, 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, 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, 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
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.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Levy reported receiving personal fees from Abiomed, Gettinge, Baxter, Novartis, Sanofi, Amomed, and Orion. Dr Girerd reported receiving personal fees from Novartis, Bayer, AstraZeneca, Lilly, Boehringer, and Vifor. Dr Besnier reported receiving personal fees from Amomed Pharma, Orion Pharma, and the Laboratoire Français du Fractionnement et des Biotechnologies (LFB). Dr Delmas reported receiving personal fees from Abiomed and Abbott Laboratories. Dr Sonneville reported receiving grants from the French Ministry of Health, the European Society of Intensive Care Medicine, and the French Society of Anesthesiology and Intensive Care Medicine. Dr Rozec reported receiving personal fees from Baxter, Aguettant, LFB, Institut Supérieur d'électronique de Paris (ISEP), Nordic Pharma, Amomed, Haemonetics, Aspen, Boston Scientific, Ethypharm, and Medtronic and nonfinancial support from ISEP. Dr Gaide-Chevronnay reported receiving personal fees from LFB. Dr Rossignol reported receiving personal fees from Idorsia, G3P, CinCor, AstraZeneca, Bayer, Grunenthal, CVRx, Novartis, Novo Nordisk, Relypsa, Roche, Servier, Stealth Peptides, and Vifor Fresenius Medical Care Renal Pharma; receiving grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma; and being the co-founder of CardioRenal. Dr Kimmoun reported receiving personal fees from Aspen and Aguettant. Dr Slutsky reported receiving personal fees from Baxter, Xenios, and Fresenius Medical Care and being the chair of the scientific committee of the International ECMO Network. Dr Brodie reported receiving grants from ALung Technologies; serving on medical advisory boards and receiving personal fees from Abiomed, Xenios, Medtronic, and Cellenkos; and being the president-elect of the Extracorporeal Life Support Organization and the chair of the executive committee of the International ECMO Network. Dr Ouattara reported receiving personal fees from Abiomed, Nordic Pharma, LFB, VifOR Pharma, Orion Pharma, ISEP, Masimo, and Medtronic. Dr Combes reported receiving personal fees from Getinge, Baxter, and Fresenius-Xenios. No other disclosures were reported.
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Source: PubMed