Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

doi:10.1186/s13613-022-01038-0

Review

. 2022 Jul 2;12(1):58.

doi: 10.1186/s13613-022-01038-0.

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Guillaume Voiriot¹, Mehdi Oualha², Alexandre Pierre^{3

4

5}, Charlotte Salmon-Gandonnière⁶, Alexandre Gaudet^{4

5

7}, Youenn Jouan⁶, Hatem Kallel⁸, Peter Radermacher⁹, Dominique Vodovar^{10

11

12}, Benjamine Sarton^{13

14}, Laure Stiel^{15

16}, Nicolas Bréchot^{17

18}, Sébastien Préau^{3

6}, Jérémie Joffre^{19

20

21}; la CRT de la SRLF

Affiliations

¹ Service de Médecine Intensive Réanimation, Hôpital Tenon, Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Paris, France.
² Pediatric Intensive Care Unit, Necker Hospital, APHP, Centre - Paris University, Paris, France.
³ Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, University Lille, Inserm, CHU Lille, 59000, Lille, France.
⁴ Department of Intensive Care Medicine, Critical Care Center, CHU Lille, 59000, Lille, France.
⁵ Faculté de Médecine de Tours, Centre d'Etudes des Pathologies Respiratoires, INSERM U1100, University Lille, Tours, France.
⁶ Service de Médecine Intensive Réanimation, CHRU de Tours, Réseau CRICS-TRIGGERSEP F-CRIN Research Network, Tours, France.
⁷ Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d'Infection et d'Immunité de Lille, 59000, Lille, France.
⁸ Service de Réanimation, Centre Hospitalier de Cayenne, French Guiana, Cayenne, France.
⁹ Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, 89070, Ulm, Germany.
¹⁰ Centre AntiPoison de Paris, Hôpital Fernand Widal, APHP, 75010, Paris, France.
¹¹ Faculté de Pharmacie, UMRS 1144, 75006, Paris, France.
¹² Université de Paris, UFR de Médecine, 75010, Paris, France.
¹³ Critical Care Unit, University Hospital of Purpan, Toulouse, France.
¹⁴ Toulouse NeuroImaging Center, ToNIC, Inserm 1214, Paul Sabatier University, Toulouse, France.
¹⁵ Service de Réanimation Médicale, Groupe Hospitalier de la Région Mulhouse Sud Alsace, Mulhouse, France.
¹⁶ INSERM, LNC UMR 1231, FCS Bourgogne Franche Comté LipSTIC LabEx, Dijon, France.
¹⁷ Service de Médecine Intensive Réanimation, Sorbonne Université, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹⁸ College de France, Center for Interdisciplinary Research in Biology (CIRB)-UMRS INSERM U1050 - CNRS 7241, Paris, France.
¹⁹ Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, 94143, USA. jeremie.joffre@aphp.fr.
²⁰ Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France. jeremie.joffre@aphp.fr.
²¹ Sorbonne University, Centre de Recherche Saint-Antoine INSERM U938, 75012, Paris, France. jeremie.joffre@aphp.fr.

PMID: 35779142
PMCID: PMC9250584
DOI: 10.1186/s13613-022-01038-0

Review

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Guillaume Voiriot et al. Ann Intensive Care. 2022.

. 2022 Jul 2;12(1):58.

doi: 10.1186/s13613-022-01038-0.

Authors

Affiliations

¹ Service de Médecine Intensive Réanimation, Hôpital Tenon, Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Paris, France.
² Pediatric Intensive Care Unit, Necker Hospital, APHP, Centre - Paris University, Paris, France.
³ Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, University Lille, Inserm, CHU Lille, 59000, Lille, France.
⁴ Department of Intensive Care Medicine, Critical Care Center, CHU Lille, 59000, Lille, France.
⁵ Faculté de Médecine de Tours, Centre d'Etudes des Pathologies Respiratoires, INSERM U1100, University Lille, Tours, France.
⁶ Service de Médecine Intensive Réanimation, CHRU de Tours, Réseau CRICS-TRIGGERSEP F-CRIN Research Network, Tours, France.
⁷ Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d'Infection et d'Immunité de Lille, 59000, Lille, France.
⁸ Service de Réanimation, Centre Hospitalier de Cayenne, French Guiana, Cayenne, France.
⁹ Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, 89070, Ulm, Germany.
¹⁰ Centre AntiPoison de Paris, Hôpital Fernand Widal, APHP, 75010, Paris, France.
¹¹ Faculté de Pharmacie, UMRS 1144, 75006, Paris, France.
¹² Université de Paris, UFR de Médecine, 75010, Paris, France.
¹³ Critical Care Unit, University Hospital of Purpan, Toulouse, France.
¹⁴ Toulouse NeuroImaging Center, ToNIC, Inserm 1214, Paul Sabatier University, Toulouse, France.
¹⁵ Service de Réanimation Médicale, Groupe Hospitalier de la Région Mulhouse Sud Alsace, Mulhouse, France.
¹⁶ INSERM, LNC UMR 1231, FCS Bourgogne Franche Comté LipSTIC LabEx, Dijon, France.
¹⁷ Service de Médecine Intensive Réanimation, Sorbonne Université, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹⁸ College de France, Center for Interdisciplinary Research in Biology (CIRB)-UMRS INSERM U1050 - CNRS 7241, Paris, France.
¹⁹ Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, 94143, USA. jeremie.joffre@aphp.fr.
²⁰ Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France. jeremie.joffre@aphp.fr.
²¹ Sorbonne University, Centre de Recherche Saint-Antoine INSERM U938, 75012, Paris, France. jeremie.joffre@aphp.fr.

PMID: 35779142
PMCID: PMC9250584
DOI: 10.1186/s13613-022-01038-0

Abstract

Background: Post-intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long-term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions.

Main text: This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child's pre-ICU condition, development, and maturation.

Conclusions: Recent understandings of the biological substratum of the PICS' distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery.

Keywords: Acquired immunosuppression; Chronic critical illness; Cognitive impairment; ICU sequelae; Long-term outcome; Neuromuscular disorders; Post-ICU syndrome.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
ICU survivors with post-intensive care syndrome. Clinical characteristics and consequences, and futures research directions for each long-lasting sub-syndrome after ICU stay

**Fig. 2**
Putative mechanisms of intensive care unit‐acquired weakness

**Fig. 3**
Putative mechanisms of ICU-acquired immune deficiency

**Fig. 4**
Mechanisms underlying progression toward chronic kidney disease after AKI

See this image and copyright information in PMC

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References

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1. Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129–1140. doi: 10.1016/j.chest.2016.03.045. - DOI - PMC - PubMed
1. Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014;190(4):410–20. doi: 10.1164/rccm.201312-2257OC. - DOI - PubMed
1. Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020;46(6):1184–1193. doi: 10.1007/s00134-020-05927-5. - DOI - PubMed
1. Saccheri C, Morawiec E, Delemazure J, Mayaux J, Dube BP, Similowski T, et al. ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients. Ann Intensive Care. 2020;10(1):1. doi: 10.1186/s13613-019-0618-4. - DOI - PMC - PubMed

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[1] Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311(13):1308–1316. doi: 10.1001/jama.2014.2637. - DOI - PubMed

[2] Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311(13):1308–1316. doi: 10.1001/jama.2014.2637. - DOI - PubMed

[3] Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129–1140. doi: 10.1016/j.chest.2016.03.045. - DOI - PMC - PubMed

[4] Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129–1140. doi: 10.1016/j.chest.2016.03.045. - DOI - PMC - PubMed

[5] Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014;190(4):410–20. doi: 10.1164/rccm.201312-2257OC. - DOI - PubMed

[6] Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014;190(4):410–20. doi: 10.1164/rccm.201312-2257OC. - DOI - PubMed

[7] Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020;46(6):1184–1193. doi: 10.1007/s00134-020-05927-5. - DOI - PubMed

[8] Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020;46(6):1184–1193. doi: 10.1007/s00134-020-05927-5. - DOI - PubMed

[9] Saccheri C, Morawiec E, Delemazure J, Mayaux J, Dube BP, Similowski T, et al. ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients. Ann Intensive Care. 2020;10(1):1. doi: 10.1186/s13613-019-0618-4. - DOI - PMC - PubMed

[10] Saccheri C, Morawiec E, Delemazure J, Mayaux J, Dube BP, Similowski T, et al. ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients. Ann Intensive Care. 2020;10(1):1. doi: 10.1186/s13613-019-0618-4. - DOI - PMC - PubMed

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Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Affiliations

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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Cited by

References

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Abstract

Conflict of interest statement

Figures

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References

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