Pathophysiological Insights into Post-Intensive Care Syndrome: Bridging Critical Illness and Long-Term Dysfunction
-
Fatemeh Afra
,
Khashayar Shahverdi
,
Leila Sadat Hosseini
,
Hanieh Jalalian
,
Parsa Dokhani
,
Negin Davoudi
,
Ziba Aghsaeifard
,
Atabak Najafi
,
Amirmahdi Mojtahedzadeh
,
Mojtaba Mojtahedzadeh
Abstract
Background: Post-intensive care syndrome (PICS) is a frequent complication of critical illness characterized by persistent physical, cognitive, psychological, and cardiopulmonary impairments. This narrative review summarizes the biological mechanisms underlying PICS and current approaches to its prevention and management.
Methods: A narrative review of contemporary experimental and clinical literature was performed to synthesize evidence on the pathophysiology, prevention, rehabilitation, and long-term management of PICS.
Results: PICS is driven by interconnected mechanisms and pathways. These pathways contribute to intensive care unit (ICU)-acquired weakness, cognitive impairment, psychological disorders, and chronic cardiopulmonary dysfunction. Emerging strategies, including biological phenotyping, multi-omics technologies, and precision rehabilitation, may facilitate individualized recovery. The review also highlights the impact of PICS on family members (PICS-F).
Conclusion: PICS is a heterogeneous multisystem condition requiring an integrated approach from ICU care through long-term rehabilitation. A better understanding of its biological mechanisms may support personalized interventions and improve long-term outcomes for ICU survivors and their families.
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[10] Vanhorebeek I, Latronico N, Van den Berghe G. ICU-acquired weakness. Intensive Care Med. 2020; 46(4):637-53.
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[13] Fazzini B, Märkl T, Costas C, Blobner M, Schaller SJ, et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care. 2023; 27(1):2.
[14] Stevens RD, Marshall SA, Cornblath DR, Hoke A, Needham DM, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Crit Care Med. 2009; 37(10 Suppl):S299-308.
[15] Fan E, Cheek F, Chlan L, Gosselink R, Hart N, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014; 190(12):1437-46.
[16] Wang W, Xu C, Ma X, Zhang X, Xie P. Intensive Care Unit-Acquired Weakness: A Review of Recent Progress With a Look Toward the Future. Front Med (Lausanne). 2020; 7:559789.
[17] de Letter MA, Schmitz PI, Visser LH, Verheul FA, Schellens RL, et al. Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med. 2001; 29(12):2281-6.
[18] Eikermann M, Koch G, Gerwig M, Ochterbeck C, Beiderlinden M, et al. Muscle force and fatigue in patients with sepsis and multiorgan failure. Intensive Care Med. 2006; 32(2):251-9.
[19] Weber-Carstens S, Deja M, Koch S, Spranger J, Bubser F, et al. Risk factors in critical illness myopathy during the early course of critical illness: a prospective observational study. Crit Care. 2010; 14(3):R119.
[20] Friedrich O, Reid MB, Van den Berghe G, Vanhorebeek I, Hermans G, et al. The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill. Physiol Rev. 2015; 95(3):1025-109.
[21] Crossland H, Skirrow S, Puthucheary ZA, Constantin-Teodosiu D, Greenhaff PL. The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points. J Physiol. 2019; 597(5):1259-70.
[22] Bloch S, Polkey MI, Griffiths M, Kemp P. Molecular mechanisms of intensive care unit-acquired weakness. Eur Respir J. 2012; 39(4):1000-11.
[23] Kalamgi RC, Larsson L. Mechanical Signaling in the Pathophysiology of Critical Illness Myopathy. Front Physiol. 2016; 7:23.
[24] Levine S, Biswas C, Dierov J, Barsotti R, Shrager JB, et al. Increased proteolysis, myosin depletion, and atrophic AKT-FOXO signaling in human diaphragm disuse. Am J Respir Crit Care Med. 2011; 183(4):483-90.
[25] Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008; 451(7182):1069-75.
[26] Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve. 2005; 32(2):140-63.
[27] Rudolf R, Deschenes MR, Sandri M. Neuromuscular junction degeneration in muscle wasting. Curr Opin Clin Nutr Metab Care. 2016; 19(3):177-81.
[28] Needham DM, Dinglas VD, Morris PE, Jackson JC, Hough CL, et al. Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. EDEN trial follow-up. Am J Respir Crit Care Med. 2013; 188(5):567-76.
[29] Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013; 369(14):1306-16.
[30] Davydow DS, Zatzick D, Hough CL, Katon WJ. In-hospital acute stress symptoms are associated with impairment in cognition 1 year after intensive care unit admission. Ann Am Thorac Soc. 2013; 10(5):450-7.
[31] Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, et al. Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005; 171(4):340-7.
[32] Rawal G, Yadav S, Kumar R. Post-traumatic stress disorder: a review from clinical perspective. Int J Indian Psychol. 2016; 3(2):157-64.
[33] Hatch R, Young D, Barber V, Griffiths J, Harrison DA, et al. Anxiety, Depression and Post Traumatic Stress Disorder after critical illness: a UK-wide prospective cohort study. Crit Care. 2018; 22(1):310.
[34] Mikkelsen ME, Christie JD, Lanken PN, Biester RC, Thompson BT, et al. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med. 2012; 185(12):1307-15.
[35] Altman MT, Knauert MP, Pisani MA. Sleep Disturbance after Hospitalization and Critical Illness: A Systematic Review. Ann Am Thorac Soc. 2017; 14(9):1457-68.
[36] Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010; 304(16):1787-94.
[37] Wunsch H, Christiansen CF, Johansen MB, Olsen M, Ali N, et al. Psychiatric diagnoses and psychoactive medication use among nonsurgical critically ill patients receiving mechanical ventilation. JAMA. 2014; 311(11):1133-42.
[38] Jackson JC, Pandharipande PP, Girard TD, Brummel NE, Thompson JL, et al. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med. 2014; 2(5):369-79.
[39] Sakusic A, Rabinstein AA. Cognitive outcomes after critical illness. Curr Opin Crit Care. 2018; 24(5):410-4.
[40] González-López A, López-Alonso I, Aguirre A, Amado-Rodríguez L, Batalla-Solís E, et al. Mechanical ventilation triggers hippocampal apoptosis by vagal and dopaminergic pathways. Am J Respir Crit Care Med. 2013; 188(6):693-702.
[41] Hughes CG, Morandi A, Girard TD, Riedel B, Thompson JL, et al. Association between endothelial dysfunction and acute brain dysfunction during critical illness. Anesthesiology. 2013; 118(3):631-9.
[42] Sekino N, Selim M, Shehadah A. Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments. J Neuroinflammation. 2022; 19(1):101.
[43] Martín-Vicente P, López-Martínez C, Lopez-Alonso I, López-Aguilar J, Albaiceta GM, et al. Molecular mechanisms of postintensive care syndrome. Intensive Care Med Exp. 2021; 9(1):58.
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| Section | Review Article(s) | |
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| Critical Illness Intensive Care Units (ICU) Post-Intensive Care Syndrome (PICS) Rehabilitation Muscle Weakness | ||
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How to Cite
1.
Afra F, Shahverdi K, Hosseini LS, Jalalian H, Dokhani P, Davoudi N, Aghsaeifard Z, Najafi A, Mojtahedzadeh A, Mojtahedzadeh M. Pathophysiological Insights into Post-Intensive Care Syndrome: Bridging Critical Illness and Long-Term Dysfunction. Arch Anesth & Crit Care. 2026;.
