Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

doi:10.1056/NEJMoa1906661

Randomized Controlled Trial

. 2019 Dec 12;381(24):2327-2337.

doi: 10.1056/NEJMoa1906661. Epub 2019 Oct 2.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

Jean-Baptiste Lascarrou¹, Hamid Merdji¹, Amélie Le Gouge¹, Gwenhael Colin¹, Guillaume Grillet¹, Patrick Girardie¹, Elisabeth Coupez¹, Pierre-François Dequin¹, Alain Cariou¹, Thierry Boulain¹, Noelle Brule¹, Jean-Pierre Frat¹, Pierre Asfar¹, Nicolas Pichon¹, Mickael Landais¹, Gaëtan Plantefeve¹, Jean-Pierre Quenot¹, Jean-Charles Chakarian¹, Michel Sirodot¹, Stéphane Legriel¹, Julien Letheulle¹, Didier Thevenin¹, Arnaud Desachy¹, Arnaud Delahaye¹, Vlad Botoc¹, Sylvie Vimeux¹, Frederic Martino¹, Bruno Giraudeau¹, Jean Reignier¹; CRICS-TRIGGERSEP Group

Collaborators, Affiliations

Collaborators

CRICS-TRIGGERSEP Group:
B Giraudeau, A Le Gouge, P Asfar, F Beloncle, G Bouvier, N Chudeau, M Conte, C Darreau, A Donzeau, N Hubert, A Kouatchet, N Lerolle, F Martino, A Mercat, S Mortaza, M Pierrot, T Raveau, T Reydel, M Saint Martin, V Souday, O Baudin-Jacquemin, C Cracco, A Desachy, C Lafon, S Rouleau, D Bougon, P Charretier, R Chouquer, D Dorez, E Escudier, S Gay, S Hautefeuille, A Hyacinthe, A Levrat, M Muller, M Sirodot, D Contou, M Enser, O Pajot, G Plantefeve, M Thirion, J Tirolien, H Mentec, A Ait Hssain, C Bachelier, P Bertrand, D Brégeaud, L Calvet, L Charrier, E Coupez, A Laggoune, G Lardillon, A Lautrette, C Leroy, C Lory, R Malhomme, E Soum, B Souweine, P Andreu, R Bruyère, P E Charles, A Dargent, A Large, S Mortreux, A Pavon, S Prin, J P Quenot, J B Roudaut, A Toitot, M Azais, K Bachoumas, A Bailly, L Camous, G Colin, L Crosby, M Fiancette, M Henry Lagarrique, J C Lacherade, C Lebert, L Martin Lefevre, C Pouplet, A Seguin, I Vinatier, A Yehia, A Bildea, S Brodeur, B Derrien, F Grelon, M Landais, C Le Moal, P Tirot, D Vivier, G Gasan, M Jonard, M Lemyze, J Mallat, F Pepy, J Temime, D Thevenin, P Girardie, B Voisin, E Begot, C Chapellas, M Clavel, T Daix, A Fedou, B Francois, A Galy, C Gonzalez, C Hodler, C Mancia, N Pichon, P Vignon, G Belliard, G Grillet, P Bardou, F Bellec, M Bonnivard, A Marco, J Roustan, S Vimeux, A Delbove, N Brule, C Bretonniere, B Gaborit, C Garret, C Guitton, J B Lascarrou, A Le Meur, J Lorber, D Marest, M Martin, L Nicolet, E Pontis, J Reignier, M Vourc'h, O Zambon, F Barbier, D Benzekri, T Boulain, A Bretagnol, A Mathonnet, G Muller, M Nay, I Runge, M Skarzynski, T Kamel, S André, M Arnaout, O Ben Hadj Salem, S Bourcier, A Cariou, J D Chiche, J Charpentier, M Duprey, A Ferre, L Guillemet, M Jamme, P Jaquet, P Jaubert, J Llitjos, J P Mira, M Paul, F Pene, A Roccabianca, G Savary, S Spagnolo, S Valade, F Ardisson, K Elkoun, P Lafforgue, B Madeux, P Piednoir, B Pons, G Thiery, F Boissier, S Cabasson, D Chatellier, R Coudroy, J Dufour, J Frat, V Goudet, M Hoppe, A Jamet, F Joly, J Marechal, R Robert, A Thille, A Veinstein, P Beuret, J C Chakarian, S Devillez, X Fabre, L Gergelé, B Philippon-Jouve, C Brasse, A Delahaye, J Delmas, S Ena, P Letocart, E Moreau, N Barbarot, J Bousser, A Courte, M Debarre, P Fillatre, A Godard, A Goepp, F Legay, J Letheulle, F Marjot-Zimbacca, F Mateos, V Botoc, S Chevalier, P Detouche, J Gouêllo, N Guinard, C Quentin, P Sichel, N Anca Raluca, A Berger, A Boivin, R Clere-Jehl, X Delabranche, S Heenen, J Helms, T Khouri, C Kummerlen, H Merdji, F Meziani, A Monnier, Y Rabouël, H Rahmani, D Schnell, L Bodet Contentin, W Darwiche, P Dequin, S Ehrmann, D Garot, J Grouille, A Guillon, A Joret, Y Jouan, A Legras, C Lhommet, J Mankikian, E Mercier, M Morisseau, D Perrotin, E Rouve, C Salmon-Gandonnière, F Bruneel, J Fink, A Gros, G Lacave, V Laurent, S Legriel, S Merceron, J Moyer, C Simon, G Troché, N Zappella, B Zuber, L C Lacherade

Affiliation

¹ From Médecine Intensive Réanimation, University Hospital Center, Nantes (J.-B.L., N.B., J.R.), the Paris Cardiovascular Research Center, INSERM Unité 970 (J.-B.L., A.C.), the Medical Intensive Care Unit, Cochin University Hospital Center (A.C.), and the AfterROSC Network (J.-B.L., A.C., N.P., S.L.), Paris, Université de Strasbourg, Faculté de Médecine (H.M.), Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Service de Médecine Intensive Réanimation (H.M.), and Unité Mixte de Recherche (UMR) 1260, Regenerative Nano Medecine, INSERM, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg (H.M.), Strasbourg, INSERM Centres d'Investigation Clinique (CIC) 1415, Centre Hospitalier Régional Universitaire de Tours (A.L.G., B.G.), the Medical Intensive Care Unit, University Hospital Center (P.-F.D.), INSERM UMR 1100-Centre d'Etude des Pathologies Respiratoires, Tours University (P.-F.D.), and Université de Tours (B.G.), Tours, the Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon (G.C.), the Medical Intensive Care Unit, South Brittany General Hospital Center, Lorient (G.G.), Médecine Intensive Réanimation, Centre Hospitalier Universitaire Lille, and Université de Lille, Faculté de Médicine, Lille (P.G.), the Medical Intensive Care Unit, University Hospital Center, Clermond-Ferrand (E.C.), the Medical Intensive Care Unit, Regional Hospital Center, Orleans (T.B.), the Medical Intensive Care Unit, University Hospital Center, INSERM CIC 1402, Équipe ALIVE, and Université de Poitiers, Faculté de Médecine et de Pharmacie de Poitiers, Poitiers (J.-P.F.), the Medical Intensive Care Unit, University Hospital Center, Angers (P.A.), Service de Réanimation Polyvalente, University Hospital Center, and CIC 1435, University Hospital Center, Limoges (N.P.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Le Mans (M.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Argenteuil (G.P.), the Medical Intensive Care Unit, University Hospital Center, Dijon (J.-P.Q.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Roanne (J.-C.C.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Annecy (M.S.), the Medical-Surgical Intensive Care Unit, Versailles Hospital, Versailles (S.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Saint Brieuc (J.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Lens (D.T.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Angouleme (A. Desachy), the Medical-Surgical Intensive Care Unit, General Hospital Center, Rodez (A. Delahaye), the Medical-Surgical Intensive Care Unit, General Hospital Center, Saint Malo (V.B.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Montauban (S.V.), and the Medical Intensive Care Unit, University Hospital Center, Point-a-Pitre (F.M.) - all in France.

PMID: 31577396
DOI: 10.1056/NEJMoa1906661

Randomized Controlled Trial

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

Jean-Baptiste Lascarrou et al. N Engl J Med. 2019.

. 2019 Dec 12;381(24):2327-2337.

doi: 10.1056/NEJMoa1906661. Epub 2019 Oct 2.

Authors

Collaborators

CRICS-TRIGGERSEP Group:
B Giraudeau, A Le Gouge, P Asfar, F Beloncle, G Bouvier, N Chudeau, M Conte, C Darreau, A Donzeau, N Hubert, A Kouatchet, N Lerolle, F Martino, A Mercat, S Mortaza, M Pierrot, T Raveau, T Reydel, M Saint Martin, V Souday, O Baudin-Jacquemin, C Cracco, A Desachy, C Lafon, S Rouleau, D Bougon, P Charretier, R Chouquer, D Dorez, E Escudier, S Gay, S Hautefeuille, A Hyacinthe, A Levrat, M Muller, M Sirodot, D Contou, M Enser, O Pajot, G Plantefeve, M Thirion, J Tirolien, H Mentec, A Ait Hssain, C Bachelier, P Bertrand, D Brégeaud, L Calvet, L Charrier, E Coupez, A Laggoune, G Lardillon, A Lautrette, C Leroy, C Lory, R Malhomme, E Soum, B Souweine, P Andreu, R Bruyère, P E Charles, A Dargent, A Large, S Mortreux, A Pavon, S Prin, J P Quenot, J B Roudaut, A Toitot, M Azais, K Bachoumas, A Bailly, L Camous, G Colin, L Crosby, M Fiancette, M Henry Lagarrique, J C Lacherade, C Lebert, L Martin Lefevre, C Pouplet, A Seguin, I Vinatier, A Yehia, A Bildea, S Brodeur, B Derrien, F Grelon, M Landais, C Le Moal, P Tirot, D Vivier, G Gasan, M Jonard, M Lemyze, J Mallat, F Pepy, J Temime, D Thevenin, P Girardie, B Voisin, E Begot, C Chapellas, M Clavel, T Daix, A Fedou, B Francois, A Galy, C Gonzalez, C Hodler, C Mancia, N Pichon, P Vignon, G Belliard, G Grillet, P Bardou, F Bellec, M Bonnivard, A Marco, J Roustan, S Vimeux, A Delbove, N Brule, C Bretonniere, B Gaborit, C Garret, C Guitton, J B Lascarrou, A Le Meur, J Lorber, D Marest, M Martin, L Nicolet, E Pontis, J Reignier, M Vourc'h, O Zambon, F Barbier, D Benzekri, T Boulain, A Bretagnol, A Mathonnet, G Muller, M Nay, I Runge, M Skarzynski, T Kamel, S André, M Arnaout, O Ben Hadj Salem, S Bourcier, A Cariou, J D Chiche, J Charpentier, M Duprey, A Ferre, L Guillemet, M Jamme, P Jaquet, P Jaubert, J Llitjos, J P Mira, M Paul, F Pene, A Roccabianca, G Savary, S Spagnolo, S Valade, F Ardisson, K Elkoun, P Lafforgue, B Madeux, P Piednoir, B Pons, G Thiery, F Boissier, S Cabasson, D Chatellier, R Coudroy, J Dufour, J Frat, V Goudet, M Hoppe, A Jamet, F Joly, J Marechal, R Robert, A Thille, A Veinstein, P Beuret, J C Chakarian, S Devillez, X Fabre, L Gergelé, B Philippon-Jouve, C Brasse, A Delahaye, J Delmas, S Ena, P Letocart, E Moreau, N Barbarot, J Bousser, A Courte, M Debarre, P Fillatre, A Godard, A Goepp, F Legay, J Letheulle, F Marjot-Zimbacca, F Mateos, V Botoc, S Chevalier, P Detouche, J Gouêllo, N Guinard, C Quentin, P Sichel, N Anca Raluca, A Berger, A Boivin, R Clere-Jehl, X Delabranche, S Heenen, J Helms, T Khouri, C Kummerlen, H Merdji, F Meziani, A Monnier, Y Rabouël, H Rahmani, D Schnell, L Bodet Contentin, W Darwiche, P Dequin, S Ehrmann, D Garot, J Grouille, A Guillon, A Joret, Y Jouan, A Legras, C Lhommet, J Mankikian, E Mercier, M Morisseau, D Perrotin, E Rouve, C Salmon-Gandonnière, F Bruneel, J Fink, A Gros, G Lacave, V Laurent, S Legriel, S Merceron, J Moyer, C Simon, G Troché, N Zappella, B Zuber, L C Lacherade

Affiliation

¹ From Médecine Intensive Réanimation, University Hospital Center, Nantes (J.-B.L., N.B., J.R.), the Paris Cardiovascular Research Center, INSERM Unité 970 (J.-B.L., A.C.), the Medical Intensive Care Unit, Cochin University Hospital Center (A.C.), and the AfterROSC Network (J.-B.L., A.C., N.P., S.L.), Paris, Université de Strasbourg, Faculté de Médecine (H.M.), Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Service de Médecine Intensive Réanimation (H.M.), and Unité Mixte de Recherche (UMR) 1260, Regenerative Nano Medecine, INSERM, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg (H.M.), Strasbourg, INSERM Centres d'Investigation Clinique (CIC) 1415, Centre Hospitalier Régional Universitaire de Tours (A.L.G., B.G.), the Medical Intensive Care Unit, University Hospital Center (P.-F.D.), INSERM UMR 1100-Centre d'Etude des Pathologies Respiratoires, Tours University (P.-F.D.), and Université de Tours (B.G.), Tours, the Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon (G.C.), the Medical Intensive Care Unit, South Brittany General Hospital Center, Lorient (G.G.), Médecine Intensive Réanimation, Centre Hospitalier Universitaire Lille, and Université de Lille, Faculté de Médicine, Lille (P.G.), the Medical Intensive Care Unit, University Hospital Center, Clermond-Ferrand (E.C.), the Medical Intensive Care Unit, Regional Hospital Center, Orleans (T.B.), the Medical Intensive Care Unit, University Hospital Center, INSERM CIC 1402, Équipe ALIVE, and Université de Poitiers, Faculté de Médecine et de Pharmacie de Poitiers, Poitiers (J.-P.F.), the Medical Intensive Care Unit, University Hospital Center, Angers (P.A.), Service de Réanimation Polyvalente, University Hospital Center, and CIC 1435, University Hospital Center, Limoges (N.P.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Le Mans (M.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Argenteuil (G.P.), the Medical Intensive Care Unit, University Hospital Center, Dijon (J.-P.Q.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Roanne (J.-C.C.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Annecy (M.S.), the Medical-Surgical Intensive Care Unit, Versailles Hospital, Versailles (S.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Saint Brieuc (J.L.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Lens (D.T.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Angouleme (A. Desachy), the Medical-Surgical Intensive Care Unit, General Hospital Center, Rodez (A. Delahaye), the Medical-Surgical Intensive Care Unit, General Hospital Center, Saint Malo (V.B.), the Medical-Surgical Intensive Care Unit, General Hospital Center, Montauban (S.V.), and the Medical Intensive Care Unit, University Hospital Center, Point-a-Pitre (F.M.) - all in France.

PMID: 31577396
DOI: 10.1056/NEJMoa1906661

Abstract

Background: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated.

Methods: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed.

Results: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups.

Conclusions: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.).

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Comment in

Therapeutic hypothermia after cardiac arrest: We have found the missing piece puzzle!
Rozier R, Bruckert V, Orban JC. Rozier R, et al. Anaesth Crit Care Pain Med. 2019 Dec;38(6):573-574. doi: 10.1016/j.accpm.2019.10.008. Anaesth Crit Care Pain Med. 2019. PMID: 31785699 No abstract available.
In coma after cardiac arrest with nonshockable rhythm, therapeutic hypothermia improved 90-d neurologic outcome.
Hunter BR, Kirschner JM. Hunter BR, et al. Ann Intern Med. 2020 Feb 18;172(4):JC17. doi: 10.7326/ACPJ202002180-017. Ann Intern Med. 2020. PMID: 32066150 No abstract available.
Targeted Temperature Management for Cardiac Arrest.
Moskowitz A, Berg KM, Donnino MW. Moskowitz A, et al. N Engl J Med. 2020 Jun 25;382(26):e109. doi: 10.1056/NEJMc2011066. N Engl J Med. 2020. PMID: 32579836 No abstract available.
Targeted Temperature Management for Cardiac Arrest.
Slagt C, Tacken MCT, van Eijk LT. Slagt C, et al. N Engl J Med. 2020 Jun 25;382(26):e109. doi: 10.1056/NEJMc2011066. N Engl J Med. 2020. PMID: 32579837 No abstract available.
Targeted Temperature Management for Cardiac Arrest.
Deye N, Voicu S, Megarbane B. Deye N, et al. N Engl J Med. 2020 Jun 25;382(26):e109. doi: 10.1056/NEJMc2011066. N Engl J Med. 2020. PMID: 32579838 No abstract available.
Targeted Temperature Management for Cardiac Arrest.
van der Jagt M. van der Jagt M. N Engl J Med. 2020 Jun 25;382(26):e109. doi: 10.1056/NEJMc2011066. N Engl J Med. 2020. PMID: 32579839 No abstract available.
Targeted Temperature Management for Cardiac Arrest.
Gaieski DF. Gaieski DF. N Engl J Med. 2020 Jun 25;382(26):e109. doi: 10.1056/NEJMc2011066. N Engl J Med. 2020. PMID: 32579840 No abstract available.
Does targeted temperature management improve neurologic outcomes in patients with nonshockable rhythms?
Gossack-Keenan K, Moe J. Gossack-Keenan K, et al. CJEM. 2021 Mar;23(2):166-168. doi: 10.1007/s43678-021-00088-w. Epub 2021 Feb 9. CJEM. 2021. PMID: 33559867 No abstract available.

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Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

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Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

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