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

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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References 148

1. 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.

   Not in our library10.1001/jama.2014.2637

2. 2.

   Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129-1140.

   Not in our library10.1016/j.chest.2016.03.045

3. 3.

   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.

   Not in our library10.1164/rccm.201312-2257oc

4. 4.

   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.

   Not in our library10.1007/s00134-020-05927-5

5. 5.

   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.

   Not in our library10.1186/s13613-019-0618-4

6. 6.

   Carenzo L, Protti A, Dalla Corte F, Aceto R, Iapichino G, Milani A, et al. Short-term health-related quality of life, physical function and psychological consequences of severe COVID-19. Ann Intensive Care. 2021;11(1):91.

   Not in our library10.1186/s13613-021-00881-x

7. 7.

   Heesakkers H, van der Hoeven JG, Corsten S, Janssen I, Ewalds E, Simons KS, et al. Clinical outcomes among patients with 1-year survival following intensive care unit treatment for COVID-19. JAMA. 2022;327(6):559-565.

   Not in our library10.1001/jama.2022.0040

8. 8.

   Poulsen JB, Rose MH, Jensen BR, Moller K, Perner A. Biomechanical and nonfunctional assessment of physical capacity in male ICU survivors. Crit Care Med. 2013;41(1):93-101.

   Not in our library10.1097/ccm.0b013e31826a3f9e

9. 9.

   Solverson KJ, Grant C, Doig CJ. Assessment and predictors of physical functioning post-hospital discharge in survivors of critical illness. Ann Intensive Care. 2016;6(1):92.

   Not in our library10.1186/s13613-016-0187-8

10. 10.

    Poulsen JB, Moller K, Kehlet H, Perner A. Long-term physical outcome in patients with septic shock. Acta Anaesthesiol Scand. 2009;53(6):724-730.

    Not in our library10.1111/j.1399-6576.2009.01921.x

11. 11.

    Herridge MS, Batt J, Santos CD. ICU-acquired weakness, morbidity, and death. Am J Respir Crit Care Med. 2014;190(4):360-362.

    Not in our library10.1164/rccm.201407-1263ed

12. 12.

    Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Casaer MP, Gunst J, et al. Aerobic exercise capacity in long-term survivors of critical illness: secondary analysis of the post-EPaNIC follow-up study. Intensive Care Med. 2021;47(12):1462-1471.

    Not in our library10.1007/s00134-021-06541-9

13. 13.

    Urbina T, Canoui-Poitrine F, Hua C, Layese R, Alves A, Ouedraogo R, et al. Long-term quality of life in necrotizing soft-tissue infection survivors: a monocentric prospective cohort study. Ann Intensive Care. 2021;11(1):102.

    Not in our library10.1186/s13613-021-00891-9

14. 14.

    Yende S, Austin S, Rhodes A, Finfer S, Opal S, Thompson T, et al. Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med. 2016;44(8):1461-1467.

    Not in our library10.1097/ccm.0000000000001658

15. 15.

    Dinglas VD, Aronson Friedman L, Colantuoni E, Mendez-Tellez PA, Shanholtz CB, Ciesla ND, et al. Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med. 2017;45(3):446-453.

    Not in our library10.1097/ccm.0000000000002208

16. 16.

    Semmler A, Okulla T, Kaiser M, Seifert B, Heneka MT. Long-term neuromuscular sequelae of critical illness. J Neurol. 2013;260(1):151-157.

    Not in our library10.1007/s00415-012-6605-4

17. 17.

    Guarneri B, Bertolini G, Latronico N. Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study. J Neurol Neurosurg Psychiatry. 2008;79(7):838-841.

    Not in our library10.1136/jnnp.2007.142430

18. 18.

    Goossens C, Weckx R, Derde S, Van Helleputte L, Schneidereit D, Haug M, et al. Impact of prolonged sepsis on neural and muscular components of muscle contractions in a mouse model. J Cachexia Sarcopenia Muscle. 2021;12(2):443-455.

    Not in our library10.1002/jcsm.12668

19. 19.

    Klaude M, Fredriksson K, Tjader I, Hammarqvist F, Ahlman B, Rooyackers O, et al. Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis. Clin Sci. 2007;112(9):499-506.

    Not in our library10.1042/cs20060265

20. 20.

    Morel J, Palao JC, Castells J, Desgeorges M, Busso T, Molliex S, et al. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice. Sci Rep. 2017;7(1):10866.

    Not in our library10.1038/s41598-017-11440-5

21. 21.
    The ubiquitin–proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders · 2020

    No notice
22. 22.

    Preau S, Ambler M, Sigurta A, Kleyman A, Dyson A, Hill NE, et al. Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle. Am J Physiol Regul Integr Comp Physiol. 2019;316(5):R584-R593.

    Not in our library10.1152/ajpregu.00221.2018

23. 23.

    Vana PG, LaPorte HM, Wong YM, Kennedy RH, Gamelli RL, Majetschak M. Proteasome inhibition after burn injury. J Burn Care Res. 2016;37(4):207-215.

    Not in our library10.1097/bcr.0000000000000280

24. 24.

    Dos Santos C, Hussain SN, Mathur S, Picard M, Herridge M, Correa J, et al. Mechanisms of chronic muscle wasting and dysfunction after an intensive care unit stay. A pilot study. Am J Respir Crit Care Med. 2016;194(7):821-30.

    Not in our library10.1164/rccm.201512-2344oc

25. 25.

    Crowell KT, Soybel DI, Lang CH. Restorative mechanisms regulating protein balance in skeletal muscle during recovery from sepsis. Shock. 2017;47(4):463-473.

    Not in our library10.1097/shk.0000000000000762

26. 26.

    Gamrin-Gripenberg L, Sundstrom-Rehal M, Olsson D, Grip J, Wernerman J, Rooyackers O. An attenuated rate of leg muscle protein depletion and leg free amino acid efflux over time is seen in ICU long-stayers. Crit Care. 2018;22(1):13.

    Not in our library10.1186/s13054-017-1932-6

27. 27.

    Walsh CJ, Batt J, Herridge MS, Mathur S, Bader GD, Hu P, et al. Transcriptomic analysis reveals abnormal muscle repair and remodeling in survivors of critical illness with sustained weakness. Sci Rep. 2016;6:29334.

    Not in our library10.1038/srep29334

28. 28.

    Crowell KT, Lang CH. Contractility and myofibrillar content in skeletal muscle are decreased during post-sepsis recovery, but not during the acute phase of sepsis. Shock. 2021;55(5):649-659.

    Not in our library10.1097/shk.0000000000001555

29. 29.

    Vanhorebeek I, Gunst J, Derde S, Derese I, Boussemaere M, Guiza F, et al. Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. J Clin Endocrinol Metab. 2011;96(4):E633-E645.

    Not in our library10.1210/jc.2010-2563

30. 30.

    Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009;10(6):507-515.

    Not in our library10.1016/j.cmet.2009.10.008

31. 31.

    Masiero E, Sandri M. Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles. Autophagy. 2010;6(2):307-309.

    Not in our library10.4161/auto.6.2.11137

32. 32.

    Wagers AJ, Conboy IM. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell. 2005;122(5):659-667.

    Not in our library10.1016/j.cell.2005.08.021

33. 33.

    Walsh CJ, Escudero King C, Gupta M, Plant PJ, Herridge MJ, Mathur S, et al. MicroRNA regulatory networks associated with abnormal muscle repair in survivors of critical illness. J Cachexia Sarcopenia Muscle. 2022.

    Not in our library10.1002/jcsm.12903

34. 34.
    Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy · 2015

    No notice
35. 35.

    Jiroutkova K, Krajcova A, Ziak J, Fric M, Waldauf P, Dzupa V, et al. Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness. Crit Care. 2015;19:448.

    Not in our library10.1186/s13054-015-1160-x

36. 36.
    Energetic dysfunction in sepsis: a narrative review · 2021

    Corrected
37. 37.

    Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002;360(9328):219-223.

    Not in our library10.1016/s0140-6736(02)09459-x

38. 38.

    Owen AM, Patel SP, Smith JD, Balasuriya BK, Mori SF, Hawk GS, et al. Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model. Elife. 2019.

    Not in our library10.7554/elife.49920

39. 39.

    Balboa E, Saavedra-Leiva F, Cea LA, Vargas AA, Ramirez V, Escamilla R, et al. Sepsis-induced channelopathy in skeletal muscles is associated with expression of non-selective channels. Shock. 2018;49(2):221-228.

    Not in our library10.1097/shk.0000000000000916

40. 40.

    Segers J, Vanhorebeek I, Langer D, Charususin N, Wei W, Frickx B, et al. Early neuromuscular electrical stimulation reduces the loss of muscle mass in critically ill patients—a within subject randomized controlled trial. J Crit Care. 2021;62:65-71.

    Not in our library10.1016/j.jcrc.2020.11.018

41. 41.

    Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244-54.

    Not in our library10.1111/j.1749-6632.2000.tb06651.x

42. 42.

    Guillon A, Preau S, Aboab J, Azabou E, Jung B, Silva S, et al. Preclinical septic shock research: why we need an animal ICU. Ann Intensive Care. 2019;9(1):66.

    Not in our library10.1186/s13613-019-0543-6

43. 43.

    Shepherd SJ, Newman R, Brett SJ, Griffith DM. Enhancing rehabilitation after critical illness programme study I. Pharmacological therapy for the prevention and treatment of weakness after critical illness: a systematic review. Crit Care Med. 2016;44(6):1198-205.

    Not in our library10.1097/ccm.0000000000001652

44. 44.

    Rosenthal MD, Vanzant EL, Moore FA. Chronic critical illness and PICS nutritional strategies. J Clin Med. 2021.

    Not in our library10.3390/jcm10112294

45. 45.
    The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans · 2018

    No notice
46. 46.

    Connolly B, Salisbury L, O'Neill B, Geneen L, Douiri A, Grocott MP, et al. Exercise rehabilitation following intensive care unit discharge for recovery from critical illness: executive summary of a Cochrane Collaboration systematic review. J Cachexia Sarcopenia Muscle. 2016;7(5):520-526.

    Not in our library10.1002/jcsm.12146

47. 47.

    Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-1794.

    Not in our library10.1001/jama.2010.1553

48. 48.

    Chou CH, Lee JT, Lin CC, Sung YF, Lin CC, Muo CH, et al. Septicemia is associated with increased risk for dementia: a population-based longitudinal study. Oncotarget. 2017;8(48):84300-84308.

    Not in our library10.18632/oncotarget.20899

49. 49.

    Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

    Not in our library10.1056/nejmoa1301372

50. 50.

    Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001;344(6):395-402.

    Not in our library10.1056/nejm200102083440601

51. 51.

    Hopkins RO, Brett S. Chronic neurocognitive effects of critical illness. Curr Opin Crit Care. 2005;11(4):369-375.

    Not in our library10.1097/01.ccx.0000166399.88635.a5

52. 52.

    Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International study of post-operative cognitive dysfunction. Lancet. 1998;351(9106):857-61.

    Not in our library10.1016/s0140-6736(97)07382-0

53. 53.

    Bulic D, Bennett M, Georgousopoulou EN, Shehabi Y, Pham T, Looi JCL, et al. Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium. Ann Intensive Care. 2020;10(1):104.

    Not in our library10.1186/s13613-020-00723-2

54. 54.

    Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-1520.

    Not in our library10.1097/ccm.0b013e3181e47be1

55. 55.

    Calsavara AJC, Nobre V, Barichello T, Teixeira AL. Post-sepsis cognitive impairment and associated risk factors: a systematic review. Aust Crit Care. 2018;31(4):242-253.

    Not in our library10.1016/j.aucc.2017.06.001

56. 56.

    Calsavara AJC, Costa PA, Nobre V, Teixeira AL. Factors associated with short and long term cognitive changes in patients with sepsis. Sci Rep. 2018;8(1):4509.

    Not in our library10.1038/s41598-018-22754-3

57. 57.

    Iacobone E, Bailly-Salin J, Polito A, Friedman D, Stevens RD, Sharshar T. Sepsis-associated encephalopathy and its differential diagnosis. Crit Care Med. 2009;37(10 Suppl):S331-S336.

    Not in our library10.1097/ccm.0b013e3181b6ed58

58. 58.

    Barichello T, Martins MR, Reinke A, Feier G, Ritter C, Quevedo J, et al. Cognitive impairment in sepsis survivors from cecal ligation and perforation. Crit Care Med. 2005;33(1):221-3.

    Not in our library10.1097/01.ccm.0000150741.12906.bd

59. 59.

    Semmler A, Frisch C, Debeir T, Ramanathan M, Okulla T, Klockgether T, et al. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp Neurol. 2007;204(2):733-740.

    Not in our library10.1016/j.expneurol.2007.01.003

60. 60.

    de Souza Goldim MP, Della Giustina A, Mathias K, de Oliveira Junior A, Fileti ME, De Carli R, et al. Sickness behavior score is associated with neuroinflammation and late behavioral changes in polymicrobial sepsis animal model. Inflammation. 2020;43(3):1019-34.

    Not in our library10.1007/s10753-020-01187-z

61. 61.

    Skelly DT, Griffin EW, Murray CL, Harney S, O'Boyle C, Hennessy E, et al. Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms. Mol Psychiatry. 2019;24(10):1533-1548.

    Not in our library10.1038/s41380-019-0403-7

62. 62.

    Schaefer ST, Koenigsperger S, Olotu C, Saller T. Biomarkers and postoperative cognitive function: could it be that easy? Curr Opin Anaesthesiol. 2019;32(1):92-100.

    Not in our library10.1097/aco.0000000000000676

63. 63.

    Franck M, Nerlich K, Neuner B, Schlattmann P, Brockhaus WR, Spies CD, et al. No convincing association between post-operative delirium and post-operative cognitive dysfunction: a secondary analysis. Acta Anaesthesiol Scand. 2016;60(10):1404-1414.

    Not in our library10.1111/aas.12779

64. 64.

    Amabili P, Wozolek A, Noirot I, Roediger L, Senard M, Donneau AF, et al. The edmonton frail scale improves the prediction of 30-day mortality in elderly patients undergoing cardiac surgery: a prospective observational study. J Cardiothorac Vasc Anesth. 2019;33(4):945-952.

    Not in our library10.1053/j.jvca.2018.05.038

65. 65.

    Hall RJ, Watne LO, Cunningham E, Zetterberg H, Shenkin SD, Wyller TB, et al. CSF biomarkers in delirium: a systematic review. Int J Geriatr Psychiatry. 2018;33(11):1479-1500.

    Not in our library10.1002/gps.4720

66. 66.
    Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery · 2016

    No notice
67. 67.
    Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) – short version · 2015

    No notice
68. 68.

    Mietani K, Sumitani M, Ogata T, Shimojo N, Inoue R, Abe H, et al. Dysfunction of the blood-brain barrier in postoperative delirium patients, referring to the axonal damage biomarker phosphorylated neurofilament heavy subunit. PLoS ONE. 2019;14(10):e0222721.

    Not in our library10.1371/journal.pone.0222721

69. 69.

    Morandi A, Rogers BP, Gunther ML, Merkle K, Pandharipande P, Girard TD, et al. The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*. Crit Care Med. 2012;40(7):2182-2189.

    Not in our library10.1097/ccm.0b013e318250acdc

70. 70.

    Hughes CG, Morandi A, Girard TD, Riedel B, Thompson JL, Shintani AK, et al. Association between endothelial dysfunction and acute brain dysfunction during critical illness. Anesthesiology. 2013;118(3):631-639.

    Not in our library10.1097/aln.0b013e31827bd193

71. 71.

    Demaret J, Venet F, Friggeri A, Cazalis MA, Plassais J, Jallades L, et al. Marked alterations of neutrophil functions during sepsis-induced immunosuppression. J Leukoc Biol. 2015;98(6):1081-1090.

    Not in our library10.1189/jlb.4a0415-168rr

72. 72.

    Guerin E, Orabona M, Raquil MA, Giraudeau B, Bellier R, Gibot S, et al. Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*. Crit Care Med. 2014;42(9):2007-2018.

    Not in our library10.1097/ccm.0000000000000344

73. 73.

    Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013;25(4):477-483.

    Not in our library10.1016/j.coi.2013.05.006

74. 74.

    Winkler MS, Rissiek A, Priefler M, Schwedhelm E, Robbe L, Bauer A, et al. Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFalpha response: a diagnostic tool for immunosuppression? PLoS ONE. 2017;12(8):e0182427.

    Not in our library10.1371/journal.pone.0182427

75. 75.
    Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis · 2019

    Not checked
76. 76.

    Uhel F, Azzaoui I, Gregoire M, Pangault C, Dulong J, Tadie JM, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(3):315-327.

    Not in our library10.1164/rccm.201606-1143oc

77. 77.

    Loftus TJ, Mohr AM, Moldawer LL. Dysregulated myelopoiesis and hematopoietic function following acute physiologic insult. Curr Opin Hematol. 2018;25(1):37-43.

    Not in our library10.1097/moh.0000000000000395

78. 78.

    Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock. 2014;42(5):383-391.

    Not in our library10.1097/shk.0000000000000234

79. 79.

    Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166(11):6952-6963.

    Not in our library10.4049/jimmunol.166.11.6952

80. 80.

    Monserrat J, de Pablo R, Diaz-Martin D, Rodriguez-Zapata M, de la Hera A, Prieto A, et al. Early alterations of B cells in patients with septic shock. Crit Care. 2013;17(3):R105.

    Not in our library10.1186/cc12750

81. 81.

    Shankar-Hari M, Fear D, Lavender P, Mare T, Beale R, Swanson C, et al. Activation-associated accelerated apoptosis of memory b cells in critically ill patients with sepsis. Crit Care Med. 2017;45(5):875-882.

    Not in our library10.1097/ccm.0000000000002380

82. 82.

    Dong X, Liu Q, Zheng Q, Liu X, Wang Y, Xie Z, et al. Alterations of B cells in immunosuppressive phase of septic shock patients. Crit Care Med. 2020;48(6):815-821.

    Not in our library10.1097/ccm.0000000000004309

83. 83.

    Venet F, Davin F, Guignant C, Larue A, Cazalis MA, Darbon R, et al. Early assessment of leukocyte alterations at diagnosis of septic shock. Shock. 2010;34(4):358-363.

    Not in our library10.1097/shk.0b013e3181dc0977

84. 84.
    CD4 T Cell Responses and the Sepsis-Induced Immunoparalysis State · 2020

    No notice
85. 85.

    Danahy DB, Strother RK, Badovinac VP, Griffith TS. Clinical and experimental sepsis impairs CD8 T-cell-mediated immunity. Crit Rev Immunol. 2016;36(1):57-74.

    Not in our library10.1615/critrevimmunol.2016017098

86. 86.

    Farber DL. Tissues, not blood, are where immune cells function. Nature. 2021;593(7860):506-509.

    Not in our library10.1038/d41586-021-01396-y

87. 87.

    Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81(5):442-448.

    Not in our library10.1038/ki.2011.379

88. 88.

    Horkan CM, Purtle SW, Mendu ML, Moromizato T, Gibbons FK, Christopher KB. The association of acute kidney injury in the critically ill and postdischarge outcomes: a cohort study*. Crit Care Med. 2015;43(2):354-364.

    Not in our library10.1097/ccm.0000000000000706

89. 89.

    Wu VC, Wu CH, Huang TM, Wang CY, Lai CF, Shiao CC, et al. Long-term risk of coronary events after AKI. J Am Soc Nephrol. 2014;25(3):595-605.

    Not in our library10.1681/asn.2013060610

90. 90.

    Chawla LS, Amdur RL, Shaw AD, Faselis C, Palant CE, Kimmel PL. Association between AKI and long-term renal and cardiovascular outcomes in United States veterans. Clin J Am Soc Nephrol. 2014;9(3):448-456.

    Not in our library10.2215/cjn.02440213

91. 91.

    Basile DP, Bonventre JV, Mehta R, Nangaku M, Unwin R, Rosner MH, et al. Progression after AKI: understanding maladaptive repair processes to predict and identify therapeutic treatments. J Am Soc Nephrol. 2016;27(3):687-697.

    Not in our library10.1681/asn.2015030309

92. 92.

    Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014;371(1):58-66.

    Not in our library10.1056/nejmra1214243

93. 93.
    RIPK3-MLKL-mediated necroinflammation contributes to AKI progression to CKD · 2018

    No notice
94. 94.

    Szeto HH, Liu S, Soong Y, Seshan SV, Cohen-Gould L, Manichev V, et al. Mitochondria protection after acute ischemia prevents prolonged upregulation of IL-1beta and IL-18 and arrests CKD. J Am Soc Nephrol. 2017;28(5):1437-1449.

    Not in our library10.1681/asn.2016070761

95. 95.

    Perry HM, Huang L, Wilson RJ, Bajwa A, Sesaki H, Yan Z, et al. Dynamin-related protein 1 deficiency promotes recovery from AKI. J Am Soc Nephrol. 2018;29(1):194-206.

    Not in our library10.1681/asn.2017060659

96. 96.

    Baisantry A, Bhayana S, Rong S, Ermeling E, Wrede C, Hegermann J, et al. Autophagy induces prosenescent changes in proximal tubular S3 segments. J Am Soc Nephrol. 2016;27(6):1609-1616.

    Not in our library10.1681/asn.2014111059

97. 97.

    Canaud G, Brooks CR, Kishi S, Taguchi K, Nishimura K, Magassa S, et al. Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair. Sci Transl Med. 2019.

    Not in our library10.1126/scitranslmed.aav4754

98. 98.

    Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 2010;16(5):535-43.

    Not in our library10.1038/nm.2144

99. 99.

    Wilcox RR, Keselman HJ. Modern regression methods that can substantially increase power and provide a more accurate understanding of associations. Eur J Pers. 2012;26(3):165-174.

    Not in our library10.1002/per.860

100. 100.

     Basile DP, Donohoe D, Roethe K, Osborn JL. Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol. 2001;281(5):F887-F899.

     Not in our library10.1152/ajprenal.00050.2001

101. 101.

     Spurgeon KR, Donohoe DL, Basile DP. Transforming growth factor-beta in acute renal failure: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury. Am J Physiol Renal Physiol. 2005;288(3):F568-F577.

     Not in our library10.1152/ajprenal.00330.2004

102. 102.

     Zager RA, Johnson AC, Andress D, Becker K. Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury. Kidney Int. 2013;84(4):703-712.

     Not in our library10.1038/ki.2013.157

103. 103.

     Yang B, Lan S, Dieude M, Sabo-Vatasescu JP, Karakeussian-Rimbaud A, Turgeon J, et al. Caspase-3 is a pivotal regulator of microvascular rarefaction and renal fibrosis after ischemia-reperfusion injury. J Am Soc Nephrol. 2018;29(7):1900-1916.

     Not in our library10.1681/asn.2017050581

104. 104.

     Basile DP, Friedrich JL, Spahic J, Knipe N, Mang H, Leonard EC, et al. Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury. Am J Physiol Renal Physiol. 2011;300(3):F721-F733.

     Not in our library10.1152/ajprenal.00546.2010

105. 105.

     Maarouf OH, Uehara M, Kasinath V, Solhjou Z, Banouni N, Bahmani B, et al. Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing. JCI Insight. 2018.

     Not in our library10.1172/jci.insight.120546

106. 106.

     Hassoun HT, Grigoryev DN, Lie ML, Liu M, Cheadle C, Tuder RM, et al. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol. 2007;293(1):F30-40.

     Not in our library10.1152/ajprenal.00023.2007

107. 107.

     Liu M, Liang Y, Chigurupati S, Lathia JD, Pletnikov M, Sun Z, et al. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol. 2008;19(7):1360-1370.

     Not in our library10.1681/asn.2007080901

108. 108.

     Kelly KJ. Distant effects of experimental renal ischemia/reperfusion injury. J Am Soc Nephrol. 2003;14(6):1549-1558.

     Not in our library10.1097/01.asn.0000064946.94590.46

109. 109.

     Cianciolo Cosentino C, Skrypnyk NI, Brilli LL, Chiba T, Novitskaya T, Woods C, et al. Histone deacetylase inhibitor enhances recovery after AKI. J Am Soc Nephrol. 2013;24(6):943-953.

     Not in our library10.1681/asn.2012111055

110. 110.

     Kim SJ, Oh BJ, Lee JS, Lim CM, Shim TS, Lee SD, et al. Recovery from lung injury in survivors of acute respiratory distress syndrome: difference between pulmonary and extrapulmonary subtypes. Intensive Care Med. 2004;30(10):1960-1963.

     Not in our library10.1007/s00134-004-2374-6

111. 111.

     Linden VB, Lidegran MK, Frisen G, Dahlgren P, Frenckner BP, Larsen F. ECMO in ARDS: a long-term follow-up study regarding pulmonary morphology and function and health-related quality of life. Acta Anaesthesiol Scand. 2009;53(4):489-495.

     Not in our library10.1111/j.1399-6576.2008.01808.x

112. 112.

     Wilcox ME, Patsios D, Murphy G, Kudlow P, Paul N, Tansey CM, et al. Radiologic outcomes at 5 years after severe ARDS. Chest. 2013;143(4):920-926.

     Not in our library10.1378/chest.12-0685

113. 113.

     Desai SR, Wells AU, Rubens MB, Evans TW, Hansell DM. Acute respiratory distress syndrome: CT abnormalities at long-term follow-up. Radiology. 1999;210(1):29-35.

     Not in our library10.1148/radiology.210.1.r99ja2629

114. 114.

     Orme J, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(5):690-694.

     Not in our library10.1164/rccm.200206-542oc

115. 115.

     Masclans JR, Roca O, Munoz X, Pallisa E, Torres F, Rello J, et al. Quality of life, pulmonary function, and tomographic scan abnormalities after ARDS. Chest. 2011;139(6):1340-1346.

     Not in our library10.1378/chest.10-2438

116. 116.

     Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-693.

     Not in our library10.1056/nejmoa022450

117. 117.

     Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-1304.

     Not in our library10.1056/nejmoa1011802

118. 118.

     Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-2621.

     Not in our library10.1097/00003246-199912000-00002

119. 119.

     Chiumello D, Taccone P, Berto V, Marino A, Migliara G, Lazzerini M, et al. Long-term outcomes in survivors of acute respiratory distress syndrome ventilated in supine or prone position. Intensive Care Med. 2012;38(2):221-229.

     Not in our library10.1007/s00134-011-2445-4

120. 120.

     Watson RS, Choong K, Colville G, Crow S, Dervan LA, Hopkins RO, et al. Life after critical illness in children-toward an understanding of pediatric post-intensive care syndrome. J Pediatr. 2018;198:16-24.

     Not in our library10.1016/j.jpeds.2017.12.084

121. 121.

     Woodruff AG, Choong K. Long-term outcomes and the post-intensive care syndrome in critically ill children: a North American perspective. Children. 2021.

     Not in our library10.3390/children8040254

122. 122.

     Rodriguez-Rubio M, Pinto NP, Manning JC, Kudchadkar SR. Post-intensive care syndrome in paediatrics: setting our sights on survivorship. Lancet Child Adolesc Health. 2020;4(7):486-488.

     Not in our library10.1016/s2352-4642(20)30170-x

123. 123.

     Ong C, Lee JH, Leow MK, Puthucheary ZA. Functional outcomes and physical impairments in pediatric critical care survivors: a scoping review. Pediatr Crit Care Med. 2016;17(5):e247-e259.

     Not in our library10.1097/pcc.0000000000000706

124. 124.

     Pollack MM, Holubkov R, Glass P, Dean JM, Meert KL, Zimmerman J, et al. Functional Status Scale: new pediatric outcome measure. Pediatrics. 2009;124(1):e18-28.

     Not in our library10.1542/peds.2008-1987

125. 125.

     Farris RW, Weiss NS, Zimmerman JJ. Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial. Pediatr Crit Care Med. 2013;14(9):835-842.

     Not in our library10.1097/pcc.0b013e3182a551c8

126. 126.

     Choong K, Al-Harbi S, Siu K, Wong K, Cheng J, Baird B, et al. Functional recovery following critical illness in children: the “wee-cover” pilot study. Pediatr Crit Care Med. 2015;16(4):310-318.

     Not in our library10.1097/pcc.0000000000000362

127. 127.

     Als LC, Picouto MD, Hau SM, Nadel S, Cooper M, Pierce CM, et al. Mental and physical well-being following admission to pediatric intensive care. Pediatr Crit Care Med. 2015;16(5):e141-e149.

     Not in our library10.1097/pcc.0000000000000424

128. 128.

     Kasinathan A, Sharawat IK, Singhi P, Jayashree M, Sahu JK, Sankhyan N. Intensive Care Unit-acquired weakness in children: a prospective observational study using simplified serial electrophysiological testing (PEDCIMP Study). Neurocrit Care. 2021;34(3):927-934.

     Not in our library10.1007/s12028-020-01123-x

129. 129.

     Field-Ridley A, Dharmar M, Steinhorn D, McDonald C, Marcin JP. ICU-acquired weakness is associated with differences in clinical outcomes in critically ill children. Pediatr Crit Care Med. 2016;17(1):53-57.

     Not in our library10.1097/pcc.0000000000000538

130. 130.

     Purser MJ, Johnston DL, McMillan HJ. Chemotherapy-induced peripheral neuropathy among paediatric oncology patients. Can J Neurol Sci. 2014;41(4):442-447.

     Not in our library10.1017/s0317167100018461

131. 131.

     Smith LS, Gharib SA, Frevert CW, Martin TR. Effects of age on the synergistic interactions between lipopolysaccharide and mechanical ventilation in mice. Am J Respir Cell Mol Biol. 2010;43(4):475-486.

     Not in our library10.1165/rcmb.2009-0039oc

132. 132.

     Nardell EA, Brody JS. Determinants of mechanical properties of rat lung during postnatal development. J Appl Physiol Respir Environ Exerc Physiol. 1982;53(1):140-148.

     Not in our library10.1152/jappl.1982.53.1.140

133. 133.

     Yang G, Abate A, George AG, Weng YH, Dennery PA. Maturational differences in lung NF-kappaB activation and their role in tolerance to hyperoxia. J Clin Invest. 2004;114(5):669-678.

     Not in our library10.1172/jci200419300

134. 134.

     Ygberg S, Nilsson A. The developing immune system—from foetus to toddler. Acta Paediatr. 2012;101(2):120-127.

     Not in our library10.1111/j.1651-2227.2011.02494.x

135. 135.

     Ghazal P, Dickinson P, Smith CL. Early life response to infection. Curr Opin Infect Dis. 2013;26(3):213-218.

     Not in our library10.1097/qco.0b013e32835fb8bf

136. 136.

     Kneyber MC, Zhang H, Slutsky AS. Ventilator-induced lung injury. Similarity and differences between children and adults. Am J Respir Crit Care Med. 2014;190(3):258-65.

     Not in our library10.1164/rccm.201401-0168cp

137. 137.

     Pollack MM, Holubkov R, Funai T, Clark A, Moler F, Shanley T, et al. Relationship between the functional status scale and the pediatric overall performance category and pediatric cerebral performance category scales. JAMA Pediatr. 2014;168(7):671-676.

     Not in our library10.1001/jamapediatrics.2013.5316

138. 138.

     Bone MF, Feinglass JM, Goodman DM. Risk factors for acquiring functional and cognitive disabilities during admission to a PICU*. Pediatr Crit Care Med. 2014;15(7):640-648.

     Not in our library10.1097/pcc.0000000000000199

139. 139.

     Fink EL, Kochanek PM, Tasker RC, Beca J, Bell MJ, Clark RS, et al. International survey of critically ill children with acute neurologic insults: the prevalence of acute critical neurological disease in children: a global epidemiological assessment study. Pediatr Crit Care Med. 2017;18(4):330-342.

     Not in our library10.1097/pcc.0000000000001093

140. 140.

     Failla MD, Juengst SB, Arenth PM, Wagner AK. Preliminary associations between brain-derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI. Neurorehabil Neural Repair. 2016;30(5):419-430.

     Not in our library10.1177/1545968315600525

141. 141.

     Park SH, Hwang SK. Prognostic value of serum levels of S100 calcium-binding protein B, neuron-specific enolase, and interleukin-6 in pediatric patients with traumatic brain injury. World Neurosurg. 2018;118:e534-e542.

     Not in our library10.1016/j.wneu.2018.06.234

142. 142.

     Fink EL, Berger RP, Clark RS, Watson RS, Angus DC, Richichi R, et al. Serum biomarkers of brain injury to classify outcome after pediatric cardiac arrest*. Crit Care Med. 2014;42(3):664-674.

     Not in our library10.1097/01.ccm.0000435668.53188.80

143. 143.

     Madurski C, Jarvis JM, Beers SR, Houtrow AJ, Wagner AK, Fabio A, et al. Serum biomarkers of regeneration and plasticity are associated with functional outcome in pediatric neurocritical illness: an exploratory study. Neurocrit Care. 2021;35(2):457-467.

     Not in our library10.1007/s12028-021-01199-z

144. 144.

     Lopes-Junior LC, Rosa M, Lima RAG. Psychological and psychiatric outcomes following PICU admission: a systematic review of cohort studies. Pediatr Crit Care Med. 2018;19(1):e58-e67.

     Not in our library10.1097/pcc.0000000000001390

145. 145.

     Rees G, Gledhill J, Garralda ME, Nadel S. Psychiatric outcome following paediatric intensive care unit (PICU) admission: a cohort study. Intensive Care Med. 2004;30(8):1607-1614.

     Not in our library10.1007/s00134-004-2310-9

146. 146.

     Colville G, Kerry S, Pierce C. Children’s factual and delusional memories of intensive care. Am J Respir Crit Care Med. 2008;177(9):976-982.

     Not in our library10.1164/rccm.200706-857oc

147. 147.

     Manning JC, Hemingway P, Redsell SA. Stories of survival: children’s narratives of psychosocial well-being following paediatric critical illness or injury. J Child Health Care. 2017;21(3):236-252.

     Not in our library10.1177/1367493517717078

148. 148.

     Nelson LP, Gold JI. Posttraumatic stress disorder in children and their parents following admission to the pediatric intensive care unit: a review. Pediatr Crit Care Med. 2012;13(3):338-347.

     Not in our library10.1097/pcc.0b013e3182196a8f

Cited by papers we hold 1

• Virtual and augmented reality in critical care medicine: the patient’s, clinician’s, and researcher’s perspective · 2022
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