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

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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.

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Most cited references 151

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Inflamm-aging. An evolutionary perspective on immunosenescence.

C Franceschi, M BonaFe, S Valensin … (2000)

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

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Inflamm-aging: An Evolutionary Perspective on Immunosenescence

Claudio Franceschi, MASSIMILIANO BONAFÈ, SILVANA VALENSIN … (2000)

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Long-term cognitive impairment after critical illness.

P.P. Pandharipande, T.D. Girard, J.C. Jackson … (2013)

Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

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Author and article information

Contributors

Jérémie Joffre:

ORCID: http://orcid.org/0000-0003-4465-8392

jeremie.joffre@aphp.fr

Journal

Journal ID (nlm-ta): Ann Intensive Care

Journal ID (iso-abbrev): Ann Intensive Care

Title: Annals of Intensive Care

Publisher: Springer International Publishing (Cham )

ISSN (Electronic): 2110-5820

Publication date (Electronic): 2 July 2022

Publication date PMC-release: 2 July 2022

Publication date Collection: 2022

Volume: 12

Electronic Location Identifier: 58

Affiliations

[1 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Service de Médecine Intensive Réanimation, Hôpital Tenon, , Sorbonne Université, Assistance Publique - Hôpitaux de Paris, ; Paris, France

[2 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Pediatric Intensive Care Unit, Necker Hospital, , APHP, Centre - Paris University, ; Paris, France

[3 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, 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 ]GRID grid.410463.4, ISNI 0000 0004 0471 8845, Department of Intensive Care Medicine, Critical Care Center, , CHU Lille, ; 59000 Lille, France

[5 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, Faculté de Médecine de Tours, Centre d’Etudes des Pathologies Respiratoires, , INSERM U1100, University Lille, ; Tours, France

[6 ]GRID grid.411167.4, ISNI 0000 0004 1765 1600, Service de Médecine Intensive Réanimation, CHRU de Tours, , Réseau CRICS-TRIGGERSEP F-CRIN Research Network, ; Tours, France

[7 ]GRID grid.8970.6, ISNI 0000 0001 2159 9858, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d’Infection et d’Immunité de Lille, ; 59000 Lille, France

[8 ]GRID grid.440366.3, ISNI 0000 0004 0630 1955, Service de Réanimation, , Centre Hospitalier de Cayenne, ; French Guiana, Cayenne, France

[9 ]GRID grid.410712.1, ISNI 0000 0004 0473 882X, Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, , Universitätsklinikum Ulm, ; 89070 Ulm, Germany

[10 ]GRID grid.414095.d, ISNI 0000 0004 1797 9913, Centre AntiPoison de Paris, , Hôpital Fernand Widal, APHP, ; 75010 Paris, France

[11 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Faculté de Pharmacie, UMRS 1144, ; 75006 Paris, France

[12 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Université de Paris, UFR de Médecine, ; 75010 Paris, France

[13 ]GRID grid.414282.9, ISNI 0000 0004 0639 4960, Critical Care Unit, , University Hospital of Purpan, ; Toulouse, France

[14 ]GRID grid.15781.3a, ISNI 0000 0001 0723 035X, Toulouse NeuroImaging Center, , ToNIC, Inserm 1214, Paul Sabatier University, ; Toulouse, France

[15 ]GRID grid.490143.b, ISNI 0000 0004 6003 7868, Service de Réanimation Médicale, Groupe Hospitalier de la Région Mulhouse Sud Alsace, ; Mulhouse, France

[16 ]GRID grid.7429.8, ISNI 0000000121866389, INSERM, LNC UMR 1231, FCS Bourgogne Franche Comté LipSTIC LabEx, ; Dijon, France

[17 ]GRID grid.50550.35, ISNI 0000 0001 2175 4109, Service de Médecine Intensive Réanimation, , Sorbonne Université, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris (AP-HP), ; Paris, France

[18 ]GRID grid.410533.0, ISNI 0000 0001 2179 2236, College de France, Center for Interdisciplinary Research in Biology (CIRB)-UMRS INSERM U1050 - CNRS 7241, ; Paris, France

[19 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Anesthesia and Perioperative Care, , University of California, ; San Francisco, CA 94143 USA

[20 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Medical Intensive Care Unit, Saint Antoine University Hospital, , APHP, Sorbonne University, ; 75012 Paris, France

[21 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Sorbonne University, Centre de Recherche Saint-Antoine INSERM U938, ; 75012 Paris, France

Author information

Jérémie Joffre http://orcid.org/0000-0003-4465-8392

Article

Publisher ID: 1038

DOI: 10.1186/s13613-022-01038-0

PMC ID: 9250584

PubMed ID: 35779142

SO-VID: 27927fbd-cd17-416e-95c8-bb2f1d1c253f

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 20 April 2022

Date accepted : 20 June 2022

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: post-icu syndrome,chronic critical illness,long-term outcome,icu sequelae,neuromuscular disorders,cognitive impairment,acquired immunosuppression

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ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: post-icu syndrome, chronic critical illness, long-term outcome, icu sequelae, neuromuscular disorders, cognitive impairment, acquired immunosuppression

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

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Abstract

Background

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Conclusions

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Irish Journal of Paramedicine

Most cited references 151

Inflamm-aging. An evolutionary perspective on immunosenescence.

Inflamm-aging: An Evolutionary Perspective on Immunosenescence

Long-term cognitive impairment after critical illness.

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