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Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock

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Abstract

Purpose

Whether epinephrine or norepinephrine is preferable as the continuous intravenous vasopressor used to treat post-resuscitation shock is unclear. We assessed outcomes of patients with post-resuscitation shock after out-of-hospital cardiac arrest according to whether the continuous intravenous vasopressor used was epinephrine or norepinephrine.

Methods

We conducted an observational multicenter study of consecutive patients managed in 2011–2018 for post-resuscitation shock. The primary outcome was all-cause hospital mortality, and secondary outcomes were cardiovascular hospital mortality and unfavorable neurological outcome (Cerebral Performance Category 3–5). A multivariate regression analysis and a propensity score analysis were performed, as well as several sensitivity analyses.

Results

Of the 766 patients included in five hospitals, 285 (37%) received epinephrine and 481 (63%) norepinephrine. All-cause hospital mortality was significantly higher in the epinephrine group (OR 2.6; 95%CI 1.4–4.7; P = 0.002). Cardiovascular hospital mortality was also higher with epinephrine (aOR 5.5; 95%CI 3.0–10.3; P < 0.001), as was the proportion of patients with CPC of 3–5 at hospital discharge. Sensitivity analyses produced consistent results. The analysis involving adjustment on a propensity score to control for confounders showed similar findings (aOR 2.1; 95%CI 1.1–4.0; P = 0.02).

Conclusion

Among patients with post-resuscitation shock after out-of-hospital cardiac arrest, use of epinephrine was associated with higher all-cause and cardiovascular-specific mortality, compared with norepinephrine infusion. Until additional data become available, intensivists may want to choose norepinephrine rather than epinephrine for the treatment of post-resuscitation shock after OHCA.

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Abbreviations

AHA:

American Heart Association

CAHP:

Cardiac Arrest Hospital Prognosis

CPR:

Cardiopulmonary resuscitation

ECMO:

Extracorporeal membrane oxygenation

OHCA:

Out-of-hospital cardiac arrest

OR:

Odds ratio

RCT:

Randomized controlled trial

ROSC:

Return of spontaneous circulation

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Acknowledgements

We thank Antoinette Wolfe, MD (Fontainebleau, France), for helping to prepare the manuscript.

List of Paris Sudden Death Expertise Center investigators

F. Adnet, AP-HP, Paris 13 University, Avicenne Hospital, Emergency Medical Services (SAMU) 93, Bobigny, France. J. M. Agostinucci, AP-HP, Paris 13 University, Avicenne Hospital, Emergency Medical Services (SAMU) 93, Bobigny, France. N. Aissaoui-Balanant, AP-HP, Georges Pompidou European Hospital, Medical Intensive Care Unit, Paris, France. V. Algalarrondo, AP-HP, Antoine Beclere University Hospital, Department of Cardiology, Clamart, France. F. Alla, French National Health Insurance (CNAMTS), Paris, France. C. Alonso, Clinique Ambroise Paré, Department of Cardiology, Neuilly, France. W. Amara, Hospital Group of Montfermeil – Le Raincy, Department of Cardiology, Montfermeil, France. D. Annane, AP-HP, INSERM U1173 (Laboratory of Inflammation and Infection), University of Versailles—Saint Quentin en Yvelines, Raymond Poincare Hospital, General Intensive Care Unit, Garches, France. C. Antoine, Biomedecine agency, Saint-Denis-la-Plaine, France. P. Aubry, AP-HP, Bichat Hospital, Department of Cardiology, Paris, France. E. Azoulay, AP-HP, Paris Diderot Sorbonne University, Saint Louis Hospital, Medical Intensive Care Unit, Paris, France. F. Beganton, INSERM U970—PARCC, Paris, France. C. Billon, AP-HP, Georges Pompidou European Hospital, Department of Genetic, Paris, France. W. Bougouin, Private Hospital Jacques Cartier, Medical Intensive Care Unit, Massy, France. J. Boutet, AP-HP, Raymond Poincare Hospital, Emergency Medical Services (SAMU) 92, Garches, France. C. Bruel, Saint Joseph Hospital, Medical-Surgical Intensive Care Unit, Paris, France. P. Bruneval, AP-HP, Georges Pompidou European Hospital, Pathology Department, Paris, France. A. Cariou, AP-HP, Cochin Hospital, Medical Intensive Care Unit, Paris, France. P. Carli, AP-HP, Paris Descartes University, Necker—Enfants Malades Hospital, Emergency Medical Services (SAMU) 75, Intensive Care Unit, Paris, France. E. Casalino, AP-HP, Emergency Medical Services (SAMU) 92, Clichy, France. C. Cerf, Foch Hospital, Intensive Care Unit, Suresnes, France. A. Chaib, Andre Gregoire Hospital, Department of Cardiology, Montreuil, France. B. Cholley, AP-HP, Georges Pompidou European Hospital, Department of Anaesthesia and Surgical Intensive Care Medicine, Paris, France. Y. Cohen, AP-HP, Avicenne Hospital, Medical-Surgical Intensive Care Unit, Bobigny, France. A. Combes, AP-HP, Pitié-Salpetriere Hospital, Cardiology Institute (ICAN), Intensive Care Unit, Paris, France. J. M. Coulaud, CHI Montfermeil, Intensive Care Unit, France. M. Crahes, AP-HP, Georges Pompidou European Hospital, Pathology Department, Paris, France. D. Da Silva, Delafontaine Hospital, Intensive Care Unit, Saint-Denis, France. V. Das, Andre Gregoire Hospital, Medical-Surgical Intensive Care Unit, Montreuil, France. A. Demoule, AP-HP, Pitie Salpetriere Hospital, Medical Intensive Care Unit and Respiratory Division, Paris, France. I. Denjoy, AP-HP, Bichat Hospital, Department of Cardiology, Paris, France. N. Deye, AP-HP, Lariboisiere Hospital, Intensive Care Unit, Paris, France. J. L. Diehl, AP-HP, Georges Pompidou European Hospital, Medical Intensive Care Unit, Paris, France. S. Dinanian, AP-HP, Antoine Beclere Hospital, Department of Cardiology, Clamart, France. L. Domanski, Brigade de Sapeurs Pompiers de Paris (BSPP), Paris, France. D. Dreyfuss, AP-HP, Louis Mourier Hospital, Intensive Care Unit, Colombes, France. D. Duboc, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France. J. L. Dubois-Rande, AP-HP, Henri Mondor Hospital, Department of Cardiology, Creteil, France. F. Dumas, AP-HP, Cochin Hospital, Department of Emergency, Paris, France. J. Duranteau, AP-HP, Bicetre Hospital, Department of Anaesthesia and Intensive Care Medicine, Le Kremlin-Bicetre, France. J. P. Empana, INSERM U970—PARCC, Paris, France. F. Extramiana, AP-HP, Bichat Hospital, Department of Cardiology, Paris, France. J. Y. Fagon, AP-HP, Georges Pompidou European Hospital, Intensive Care Unit, Paris, France. M. Fartoukh, AP-HP, Sorbonne University (Paris 6), Tenon Hospital, Intensive Care Unit, Paris, France. F. Fieux, CHI Montfermeil, Intensive Care Unit, France. M. Gabbas, French National Health Insurance (CNAMTS), Paris, France. E. Gandjbakhch, AP-HP, Pitie-Salpetriere Hospital, Cardiology Institute (ICAN), Department of Cardiology, Paris, France. G.Geri, AP-HP, Ambroise Pare Hospital, Intensive Care Unit, Boulogne-Billancourt, France. B. Guidet, AP-HP, Sorbonne University (Pierre et Marie Curie University – Paris 6), Saint Antoine Hospital, Intensive Care Unit, Paris, France. F. Halimi, Private Hospital of Parly 2, Department of Cardiology, Le Chesnay, France. P. Henry, AP-HP, Sorbonne Paris Cite University (Paris Diderot University), Lariboisiere Hospital, Department of Cardiology, Paris, France. F. Hidden Lucet, AP-HP, Pitie-Salpetriere Hospital, Cardiology Institute (ICAN), Department of Cardiology, Paris, France. P. Jabre, INSERM U970 – PARCC, Emergency Medical Services (SAMU) 75, Paris, France. L. Joseph, Bicetre Hospital, Transplant Coordination, Le Kremlin-Bicetre, France. D. Jost, Brigade de Sapeurs Pompiers de Paris (BSPP), Paris, France. X. Jouven, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. N. Karam, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. H. Kassim, INSERM U970—PARCC, Paris, France. J. Lacotte, Private Hospital Jacques Cartier, Department of Cardiology, Massy, France. K. Lahlou-Laforet, AP-HP, Georges Pompidou European Hospital, Department of Psychiatry, Paris, France. L. Lamhaut, AP-HP, Paris Descartes University, Necker—Enfants Malades Hospital, Emergency Medical Services (SAMU) 75, Intensive Care Unit, Paris, France. A. Lanceleur, Foch Hospital, Intensive Care Unit, Suresnes, France. O. Langeron, AP-HP, Pitie-Salpetriere Hospital, Department of Anaesthesia and Surgical Intensive Care Medicine, Paris, France. T. Lavergne, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. E. Lecarpentier, AP-HP, Henri Mondor Hospital, Emergency Medical Services (SAMU) 94, Creteil, France. A. Leenhardt, AP-HP, Bichat Hospital, Department of Cardiology, Paris, France. N. Lellouche, AP-HP, Henri Mondor Hospital, Department of Cardiology, Creteil, France. V. Lemiale, AP-HP, Paris Diderot University, Saint Louis Hospital, Medical Intensive Care Unit, Paris, France. F. Lemoine, Brigade de Sapeurs Pompiers de Paris (BSPP), Paris, France. F. Linval, AP-HP, Paris 13 University, Avicenne Hospital, Emergency Medical Services (SAMU) 93, Bobigny, France. T. Loeb, AP-HP, Raymond Poincare Hospital, Emergency Medical Services (SAMU) 92, Garches, France. B. Ludes, Institute of Legal Medicine, Paris Descartes University, Paris, France. C. E. Luyt, AP-HP, Pitie-Salpetriere Hospital, Cardiology Institute (ICAN), Intensive Care Unit, Paris, France. A. Maltret, AP-HP, Necker—Enfants Malades Hospital, Department of Pediatric Cardiology, Paris, France. N. Mansencal, Ambroise Pare Hospital, Department of Cardiology, Boulogne-Billancourt, France. N. Mansouri, AP-HP, Henri Mondor Hospital, Emergency Medical Services (SAMU) 94, Creteil, France. E. Marijon, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. J. Marty, AP-HP, Henri Mondor Hospital, Emergency Medical Services (SAMU) 94, Creteil, France. E. Maury, AP-HP, Sorbonne University (Pierre et Marie Curie University – Paris 6), Saint Antoine Hospital, Intensive Care Unit, Paris, France. V. Maxime, AP-HP, Raymond Poincare Hospital, General Intensive Care Unit, Garches, France. B. Megarbane, AP-HP, Lariboisiere Hospital, Intensive Care Unit, Paris, France. A. Mekontso-Dessap, AP-HP, DHU A-TVB, CARMAS Research Group, Henri Mondor Hospital, Intensive Care Unit, Creteil, France. H. Mentec, Victor Dupouy Hospital, Intensive Care Unit, Argenteuil, France. J. P. Mira, AP-HP, Cochin Hospital, Medical Intensive Care Unit, Paris, France. X. Monnet, AP-HP, Bicetre Hospital, Medical Intensive Care Unit, Le Kremlin-Bicetre, France. K. Narayanan, INSERM U970—PARCC, Paris, France. N. Ngoyi, AP-HP, Paris 7 University, Beaujon Hospital, Emergency Medical Services (SAMU) 92, Clichy, France. M. C. Perier, INSERM U970—PARCC, Paris, France. O. Piot, Centre Cardiologique du Nord, Department of Cardiology, Saint-Denis, France. R. Pirracchio, AP-HP, Georges Pompidou European Hospital, Intensive Care Unit, Paris, France. P. Plaisance, Emergency Medical Services (SAMU) 75, Lariboisière SMUR, Paris, France. B. Plaud, AP-HP, Saint Louis Hospital, Department of Anaesthesia and Surgical Intensive Care Medicine, Paris, France. I. Plu, AP-HP, Pitie-Salpetriere Hospital, Neuropathology Escourolle, Paris, France. J. H. Raphalen, AP-HP, Necker—Enfants Malades Hospital, Intensive Care Unit, Paris, France. M. Raux, AP-HP, Pitié Salpétrière Hospital, Department of Anesthesiology and Critical Care, Paris, France. F. Revaux, AP-HP, Henri Mondor Hospital, Emergency Medical Services (SAMU) 94, Creteil, France. J. D. Ricard, AP-HP, Louis Mourier Hospital, Intensive Care Unit, Colombes, France. C. Richard, AP-HP, Bicetre Hospital, Medical Intensive Care Unit, Le Kremlin-Bicetre, France. B. Riou, AP-HP, Pitie-Salpetriere Hospital, Sorbonne University (Pierre et Marie Curie University – Paris 6), Department of Emergency Medicine and Surgery, Paris, France. F. Roussin, AP-HP, Saint Louis Hospital, Department of Anaesthesia and Surgical Intensive Care Medicine, Paris, France. F. Santoli, Robert Ballanger Hospital, Intensive Care Unit, Aulnay-sous-Bois, France. F. Schortgen, Centre Hospitalier Intercommunal Créteil, Intensive Care Unit, Creteil, France. A. Sharifzadehgan, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. T. Sharshar, AP-HP, Sainte Anne Hospital, Intensive Care Unit, Paris, France. G. Sideris, AP-HP, Sorbonne Paris Cite University (Paris Diderot University), Lariboisiere Hospital, Department of Cardiology, Paris, France. T. Similowski, AP-HP, Pitie-Salpetriere Hospital, Medical Intensive Care Unit and Respiratory Division, France. C. Spaulding, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France. J. L. Teboul, AP-HP, Bicetre Hospital, Medical Intensive Care Unit, Le Kremlin-Bicetre, France. J. F. Timsit, AP-HP, Bichat Hospital, Medical Intensive Care Unit, Paris, France. J. P. Tourtier, Brigade de Sapeurs Pompiers de Paris (BSPP), Paris, France. P. Tuppin, French National Health Insurance (CNAMTS), Paris, France. Ursat C, AP-HP, Raymond Poincare Hospital, Emergency Medical Services (SAMU) 92, Garches, France. O. Varenne, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France. A. Vieillard-Baron, AP-HP, Ambroise Pare Hospital, Intensive Care Unit, Boulogne-Billancourt, France. S. Voicu, AP-HP, Lariboisiere Hospital, Intensive Care Unit, Paris, France. K. Wahbi, AP-HP, Cochin Hospital, Department of Cardiology, Paris, France. V. Waldmann, AP-HP, Georges Pompidou European Hospital, Department of Cardiology, Paris, France

Funding

None.

Author information

Authors and Affiliations

  1. Paris Cardiovascular Research Center (PARCC), INSERM Unit 970, Paris, France

    Wulfran Bougouin, Kaci Slimani, Marie Renaudier, Yannick Binois, Florence Dumas, Lionel Lamhaut, Sofia Ortuno, Frankie Beganton, Daniel Jost, Eloi Marijon, Xavier Jouven, Nadia Aissaoui & Alain Cariou

  2. Ramsay Générale de Santé, Hôpital Privé Jacques Cartier, Massy, France

    Wulfran Bougouin

  3. Paris Sudden Death Expertise Center, Paris, France

    Wulfran Bougouin, Kaci Slimani, Marie Renaudier, Yannick Binois, Florence Dumas, Lionel Lamhaut, Sofia Ortuno, Frankie Beganton, Daniel Jost, Eloi Marijon, Xavier Jouven, Nadia Aissaoui & Alain Cariou

  4. Université de Paris, Paris, France

    Florence Dumas, Lionel Lamhaut, Sofia Ortuno, Eloi Marijon, Xavier Jouven, Nadia Aissaoui & Alain Cariou

  5. Emergency Department, Cochin-Hotel-Dieu Hospital, APHP, Paris, France

    Florence Dumas

  6. Intensive Care Unit and SAMU 75, Necker Enfants-Malades Hospital, Paris, France

    Lionel Lamhaut

  7. Cardiology Department, Georges Pompidou European Hospital, AP-HP, Paris, France

    Eloi Marijon & Xavier Jouven

  8. Medical ICU, Georges Pompidou European Hospital, AP-HP, Paris, France

    Sofia Ortuno & Nadia Aissaoui

  9. Medical ICU, Lariboisière Hospital, AP-HP, Paris, France

    Nicolas Deye & Sebastian Voicu

  10. Brigade de Sapeurs Pompiers de Paris (BSPP), Paris, France

    Daniel Jost

  11. Medical Intensive Care Unit, AP-HP, Cochin Teaching Hospital, 27 rue du Faubourg Saint-Jacques, 75014, Paris Cedex 14, France

    Alain Cariou

  12. Service de Médecine Intensive Réanimation, AP-HP, Hôpitaux Universitaires Henri Mondor, 94010, Créteil, France

    Armand Mekontso-Dessap

  13. Faculté de Santé, Université Paris Est Créteil, Groupe de recherche clinique CARMAS, 94010, Créteil, France

    Armand Mekontso-Dessap

  14. INSERM U955, Université Paris-Est Créteil, Créteil, France

    Armand Mekontso-Dessap

  15. SAMU des Hauts-de-Seine, APHP – Université Paris-Saclay, Hôpital Raymond Poincaré, 92 380, Garches, France

    Thomas Loeb

  16. Intensive Care Unit, Mignot Hospital, Le Chesnay, France

    Marine Paul

Authors
  1. Wulfran Bougouin
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  2. Kaci Slimani
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  3. Marie Renaudier
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  4. Yannick Binois
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  5. Marine Paul
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  6. Florence Dumas
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  7. Lionel Lamhaut
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  8. Thomas Loeb
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  9. Sofia Ortuno
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  10. Nicolas Deye
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  11. Sebastian Voicu
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  12. Frankie Beganton
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  13. Daniel Jost
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  14. Armand Mekontso-Dessap
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  15. Eloi Marijon
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  16. Xavier Jouven
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  17. Nadia Aissaoui
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  18. Alain Cariou
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Consortia

the Sudden Death Expertise Center Investigators

  • F. Adnet
  • , J. M. Agostinucci
  • , N. Aissaoui-Balanant
  • , V. Algalarrondo
  • , F. Alla
  • , C. Alonso
  • , W. Amara
  • , D. Annane
  • , C. Antoine
  • , P. Aubry
  • , E. Azoulay
  • , F. Beganton
  • , C. Billon
  • , W. Bougouin
  • , J. Boutet
  • , C. Bruel
  • , P. Bruneval
  • , A. Cariou
  • , P. Carli
  • , E. Casalino
  • , C. Cerf
  • , A. Chaib
  • , B. Cholley
  • , Y. Cohen
  • , A. Combes
  • , J. M. Coulaud
  • , M. Crahes
  • , D. Da Silva
  • , V. Das
  • , A. Demoule
  • , I Denjoy
  • , N. Deye
  • , J. L. Diehl
  • , S. Dinanian
  • , L. Domanski
  • , D. Dreyfuss
  • , D. Duboc
  • , J. L. Dubois-Rande
  • , F. Dumas
  • , J. Duranteau
  • , J. P. Empana
  • , F. Extramiana
  • , J. Y. Fagon
  • , M. Fartoukh
  • , F. Fieux
  • , M. Gabbas
  • , E. Gandjbakhch
  • , G. Geri
  • , B. Guidet
  • , F. Halimi
  • , P. Henry
  • , F. Hidden Lucet
  • , P. Jabre
  • , L. Joseph
  • , D. Jost
  • , X. Jouven
  • , N. Karam
  • , H. Kassim
  • , J. Lacotte
  • , K. Lahlou-Laforet
  • , L. Lamhaut
  • , A. Lanceleur
  • , O. Langeron
  • , T. Lavergne
  • , E. Lecarpentier
  • , A. Leenhardt
  • , N. Lellouche
  • , V. Lemiale
  • , F. Lemoine
  • , F. Linval
  • , T. Loeb
  • , B. Ludes
  • , C. E. Luyt
  • , A. Maltret
  • , N. Mansencal
  • , N. Mansouri
  • , E. Marijon
  • , J. Marty
  • , E. Maury
  • , V. Maxime
  • , B. Megarbane
  • , A. Mekontso-Dessap
  • , H. Mentec
  • , J. P. Mira
  • , X. Monnet
  • , K. Narayanan
  • , N. Ngoyi
  • , M. C. Perier
  • , O. Piot
  • , R. Pirracchio
  • , P. Plaisance
  • , B. Plaud
  • , I. Plu
  • , J. H. Raphalen
  • , M. Raux
  • , F. Revaux
  • , J. D. Ricard
  • , C. Richard
  • , B. Riou
  • , F. Roussin
  • , F. Santoli
  • , F. Schortgen
  • , A. Sharifzadehgan
  • , T. Sharshar
  • , G. Sideris
  • , T. Similowski
  • , C. Spaulding
  • , J. L. Teboul
  • , J. F. Timsit
  • , J. P. Tourtier
  • , P. Tuppin
  • , C. Ursat
  • , O. Varenne
  • , A. Vieillard-Baron
  • , S. Voicu
  • , K. Wahbi
  •  & V. Waldman

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by WB, KS, MR, YB, MP, SO, SV, FB. The first draft of the manuscript was written by WB, KS and AC, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alain Cariou.

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Conflicts of interest

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Ethics approval

The appropriate ethics committees approved the registry (CNIL approval #912309 and CCTIRS approval #12336).

Consent to participate

Appropriate IRB approved the investigation and with waiver of informed consent.

Consent for publication

Appropriate IRB approved the investigation and with waiver of informed consent.

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The Members of the Sudden Death Expertise Center Investigators are listed in the acknowledgements.

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Bougouin, W., Slimani, K., Renaudier, M. et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med 48, 300–310 (2022). https://doi.org/10.1007/s00134-021-06608-7

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