Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation
Authors: Levy Bruno , Girerd Nicolas , Amour Julien , Besnier Emmanuel , Nesseler Nicolas , Helms Julie , Delmas Clément , Sonneville Romain , Guidon Catherine , Rozec Bertrand , David Helène , Bougon David , Chaouch Oussama , Walid Oulehri , Hervé Dupont , Belin Nicolas , Gaide-Chevronnay Lucie , Rossignol Patrick , Kimmoun Antoine , Duarte Kevin , Slutsky Arthur S. , Brodie Daniel , Fellahi Jean-Luc , Ouattara Alexandre , Combes Alain ,   HYPO-ECMO Trial Group and the International ECMO Network (ECMONet), Mattei Mathieu , Thivillier Carine , Auchet Thomas , Perez Pierrre , Fritz Caroline , Maureira Pablo , Hubert Maxime , Liu Yihua , Meziani Ferhat , Merdji Hamid , Monnier Alexandra , Clere-Jehl Raphaël , Nieszkowska Ania , Pineton Marc , Chommeloux Juliette , Hékimian Guillaume , Lebreton  Guillaume , Quessard Astrid , Imbault Julien , Rémy Alain , Pernot  Mathieu , Joseph Pierre , Scollo Giovanni , Pozzi Matteo , Escudier Étienne , Muller Michel , Dorez Didier , Sirodot Michel , Doguet Fabien , Scherrer Vincent , Aludaat Chadi , Bernasinski Michael , Zogheib Elie , Caus Thierry , Bizouarn Philippe , Vourc’h Mickael , Roussel Jean-Christian , Senage Thomas , Flecher Erwan , Verhoye Jean-Philippe , Roisne Antoine , Biedermann Sébastien , Vardon-Bounes Fanny , Crognier Laure , Porterie Jean , Colson Pascal , Gaudard Philippe , Rouviere Philippe , Bouadma Lila , Sinnah Fabrice , Nataf Patrick , Para Marylou , Dureau Pauline , Djavidi Nima , Bouglé Adrien , Leprince Pascal , Dessertaine Géraldine , Durand Michel , Albaladejo Pierre , Martin Cecile , Belon François , Piton Gael , Winiszewski Hadrien , Perroti Andrea , Tonon David , Cholley Bernard , Zlotnik Diane , Achouh Paul , Nougue Hélène , Collange Olivier , Mertes Paul Michel , Kindo Michel 
Published: February 2022

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 &amp;lt;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 0.57 (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 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