Clinical Trial

. 2018 Jan 18;22(1):8.

doi: 10.1186/s13054-017-1922-8.

Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study

Etienne Gayat^{1

2}, Alain Cariou³, Nicolas Deye⁴, Antoine Vieillard-Baron⁵, Samir Jaber⁶, Charles Damoisel⁷, Qin Lu⁸, Xavier Monnet⁹, Isabelle Rennuit¹⁰, Elie Azoulay¹¹, Marc Léone¹², Heikel Oueslati⁷, Bertrand Guidet¹³, Diane Friedman¹⁴, Antoine Tesnière¹⁵, Romain Sonneville¹⁶, Philippe Montravers¹⁷, Sébastien Pili-Floury¹⁸, Jean-Yves Lefrant^{19

20}, Jacques Duranteau²¹, Pierre-François Laterre²², Nicolas Brechot²³, Karine Chevreul²⁴, Morgane Michel²⁵, Bernard Cholley²⁶, Matthieu Legrand⁷, Jean-Marie Launay²⁶, Eric Vicaut²⁷, Mervyn Singer²⁸, Matthieu Resche-Rigon²⁹, Alexandre Mebazaa⁷

Affiliations

¹ Department of Anesthesiology, Critical Care and Burn Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France. etienne.gayat@aphp.fr.
² Department of Anesthesiology and Intensive Care, University Paris Diderot, INSERM UMR-S 942, Saint Louis-Lariboisière University Hospitals, 2 rue Ambroise Paré, 75010, Paris, France. etienne.gayat@aphp.fr.
³ Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris Cardiovascular Research Center-INSERM U970 (PARCC), Paris Sudden Death Expertise Center, Paris, France.
⁴ Medical Intensive Care Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
⁵ Intensive Care Unit, University Hospital Ambroise Paré, Assistance Publique-Hopitaux de Paris, 26930, Boulogne-Billancourt, France.
⁶ Intensive Care Unit, Anaesthesia and Critical Care Department, Saint Eloi Teaching Hospital, Centre Hospitalier Universitaire Montpellier, Montpellier University, Montpellier, France.
⁷ Department of Anesthesiology, Critical Care and Burn Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
⁸ Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, UPMC Paris 6, Paris, France.
⁹ Medical Intensive Care Unit, Bicêtre Hospital, Paris-Sud University Hospitals, Inserm UMR_S999, Paris-Sud University, Le Kremlin-Bicêtre, France.
¹⁰ Department of Anesthesiology and Critical Care, Beaujon Hospital, Assistance Publique Hôpitaux de Paris University, Clichy, France.
¹¹ Medical Intensive Care Unit, Hôpital Saint-Louis, ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153 (Center of Epidemiology and Biostatistics Sorbonne Paris Cité, CRESS), INSERM, Université Paris Diderot Sorbonne, Paris, France.
¹² Service d'anesthésie et de réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France.
¹³ Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
¹⁴ General Intensive Care, Raymond Poincaré University Hosptal, Assistance Publique-Hopitaux de Paris, Garches, France.
¹⁵ Department of Anesthesiology and Intensive Care, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris Cardiovascular Research Center-INSERM U970 (PARCC), Paris Sudden Death Expertise Center, Paris, France.
¹⁶ Department of Intensive Care Medicine and Infectious Diseases, Univ Paris Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude, Paris, France.
¹⁷ Department of Anesthesiology and Intensive Care, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, Paris, France.
¹⁸ Department of Anesthesiology and Intensive Care Medicine, University Hospital of Besancon, 25000, Besancon, France.
¹⁹ Department of Anesthesiology, Emergency and Critical Care Medicine, Nimes University Hospital, 30029, Nîmes, France.
²⁰ Physiology Department, EA 2992, Faculté de Médecine de Nîmes, Université Montpellier 1, 30029, Nîmes, France.
²¹ Département d'Anesthésie-Réanimation, Hôpital de Bicêtre, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, Paris, France.
²² Medical-Surgical Intensive Care Unit, Cliniques Saint-Luc, Brussels, Belgium.
²³ Medical Intensive Care Unit, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne Pierre-Marie Curie University Paris, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition and CIC 1421-Paris Est, Paris, France.
²⁴ URC-Eco, Assistance Publique-Hôpitaux de Paris, Sorbonne Paris Cité, Université Paris Diderot, ECEVE, INSERM, Paris, France.
²⁵ Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges Pompidou, APHP, Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
²⁶ Service de Biochimie, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
²⁷ Unité de Recherche Clinique, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
²⁸ Bloomsbury Institute of Intensive Care Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
²⁹ Service de Biostatistique et Information Médicale, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, ECSTRA Team, INSERM, Paris, France.

PMID: 29347987
PMCID: PMC5774139
DOI: 10.1186/s13054-017-1922-8

Clinical Trial

Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study

Etienne Gayat et al. Crit Care. 2018.

. 2018 Jan 18;22(1):8.

doi: 10.1186/s13054-017-1922-8.

Authors

Affiliations

¹ Department of Anesthesiology, Critical Care and Burn Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France. etienne.gayat@aphp.fr.
² Department of Anesthesiology and Intensive Care, University Paris Diderot, INSERM UMR-S 942, Saint Louis-Lariboisière University Hospitals, 2 rue Ambroise Paré, 75010, Paris, France. etienne.gayat@aphp.fr.
³ Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris Cardiovascular Research Center-INSERM U970 (PARCC), Paris Sudden Death Expertise Center, Paris, France.
⁴ Medical Intensive Care Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
⁵ Intensive Care Unit, University Hospital Ambroise Paré, Assistance Publique-Hopitaux de Paris, 26930, Boulogne-Billancourt, France.
⁶ Intensive Care Unit, Anaesthesia and Critical Care Department, Saint Eloi Teaching Hospital, Centre Hospitalier Universitaire Montpellier, Montpellier University, Montpellier, France.
⁷ Department of Anesthesiology, Critical Care and Burn Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
⁸ Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, UPMC Paris 6, Paris, France.
⁹ Medical Intensive Care Unit, Bicêtre Hospital, Paris-Sud University Hospitals, Inserm UMR_S999, Paris-Sud University, Le Kremlin-Bicêtre, France.
¹⁰ Department of Anesthesiology and Critical Care, Beaujon Hospital, Assistance Publique Hôpitaux de Paris University, Clichy, France.
¹¹ Medical Intensive Care Unit, Hôpital Saint-Louis, ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153 (Center of Epidemiology and Biostatistics Sorbonne Paris Cité, CRESS), INSERM, Université Paris Diderot Sorbonne, Paris, France.
¹² Service d'anesthésie et de réanimation, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix Marseille Université, Marseille, France.
¹³ Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
¹⁴ General Intensive Care, Raymond Poincaré University Hosptal, Assistance Publique-Hopitaux de Paris, Garches, France.
¹⁵ Department of Anesthesiology and Intensive Care, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris Cardiovascular Research Center-INSERM U970 (PARCC), Paris Sudden Death Expertise Center, Paris, France.
¹⁶ Department of Intensive Care Medicine and Infectious Diseases, Univ Paris Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude, Paris, France.
¹⁷ Department of Anesthesiology and Intensive Care, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, Paris, France.
¹⁸ Department of Anesthesiology and Intensive Care Medicine, University Hospital of Besancon, 25000, Besancon, France.
¹⁹ Department of Anesthesiology, Emergency and Critical Care Medicine, Nimes University Hospital, 30029, Nîmes, France.
²⁰ Physiology Department, EA 2992, Faculté de Médecine de Nîmes, Université Montpellier 1, 30029, Nîmes, France.
²¹ Département d'Anesthésie-Réanimation, Hôpital de Bicêtre, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, Paris, France.
²² Medical-Surgical Intensive Care Unit, Cliniques Saint-Luc, Brussels, Belgium.
²³ Medical Intensive Care Unit, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne Pierre-Marie Curie University Paris, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition and CIC 1421-Paris Est, Paris, France.
²⁴ URC-Eco, Assistance Publique-Hôpitaux de Paris, Sorbonne Paris Cité, Université Paris Diderot, ECEVE, INSERM, Paris, France.
²⁵ Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges Pompidou, APHP, Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
²⁶ Service de Biochimie, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
²⁷ Unité de Recherche Clinique, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.
²⁸ Bloomsbury Institute of Intensive Care Medicine, University College London, Cruciform Building, Gower St, London, WC1E 6BT, UK.
²⁹ Service de Biostatistique et Information Médicale, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, ECSTRA Team, INSERM, Paris, France.

PMID: 29347987
PMCID: PMC5774139
DOI: 10.1186/s13054-017-1922-8

Abstract

Background: Intensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge.

Methods: FROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium. All consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following ICU admission and discharged from ICU were included. The main outcome measure was all-cause mortality at 1 year after ICU discharge. Clinical and biological parameters on ICU discharge were measured, including the circulating cardiovascular biomarkers N-terminal pro-B type natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and soluble-ST2. Socioeconomic status was assessed using a validated deprivation index (FDep).

Results: Of 1570 patients discharged alive from the ICU, 333 (21%) died over the following year. Multivariable analysis identified age, comorbidity, red blood cell transfusion, ICU length of stay and abnormalities in common clinical factors at the time of ICU discharge (low systolic blood pressure, temperature, total protein, platelet and white cell count) as independent factors associated with 1-year mortality. Elevated biomarkers of cardiac and vascular failure independently associated with 1-year death when they are added to multivariable model, with an almost 3-fold increase in the risk of death when combined (adjusted odds ratio 2.84 (95% confidence interval 1.73-4.65), p < 0.001).

Conclusions: The FROG-ICU study identified, at the time of ICU discharge, potentially actionable clinical and biological factors associated with poor long-term outcome after ICU discharge. Those factors may guide discharge planning and directed interventions.

Trial registration: ClinicalTrials.gov NCT01367093 . Registered on 6 June 2011.

Keywords: Biomarkers; Discharge; Long-term survival; Post-intensive care syndrome; Score.

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Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in France and Belgium in accordance with Good Clinical Practice (Declaration of Helsinki 2002) and Ethical Committee approvals (Comité de Protection des Personnes—Ile de France IV, IRB n°00003835 and Commission d’éthique biomédicale hospitalo-facultaire de l’hôpital de Louvain, IRB n°B403201213352).

Consent for publication

Not applicable

Competing interests

EG received research grant from Sphingotec, and consultancy fees from Magnisense and Roche Diagnostics. AM received speaker’s honoraria from Abbott, Novartis, Orion, Roche and Servier, and fees as a member of the advisory board and/or Steering Committee from Cardiorentis, Adrenomed, MyCartis, Neurotronik and Sphyngotec. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Study flow chart. *Including 27 patients with limitation of life support. ICU intensive care unit

**Fig. 2**
Clinical predictors of 1-year post-ICU survival. Area under the ROC curve of the multivariable model including the 14 variables is 0.787 (95% CI 0.759–0.815). RBC red blood cell transfusion, ICU intensive care unit, LOS length of stay, SBP systolic blood pressure, WBC white blood cell, Ref reference, OR odds ratio, CI confidence interval

**Fig. 3**
Performance of cardiovascular biomarkers at ICU discharge to predict 1-year post-ICU survival. a Kaplan–Meier curves of patients discharged alive from the ICU according to the number of cardiovascular biomarkers elevated at discharge from the ICU. b Odds ratios for the risk of 1-year mortality according to the number of cardiovascular biomarkers elevated at discharge from the ICU. Biomarkers included NT-proBNP, sST2 and bio-ADM. Nonadjusted OR are presented as black squares and OR adjusted for the 14 variables of the multivariable model as white circles. OR odds ratio, CI confidence interval

See this image and copyright information in PMC

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Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study

Affiliations

Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical