Post sepsis syndrome: an ignored enemy
DOI:
https://doi.org/10.56294/nds2025421Keywords:
Sepsis, Post ICU syndrome, Post sepsis syndrome, Rehabilitation, PrognosisAbstract
Introduction: post sepsis syndrome is an emerging entity, underrecognized in clinical practice and scarcely described in the literature. It is characterized by physical, cognitive, and psychological sequelae that affect the majority of survivors, with a negative impact on their quality of life and a significant increase in morbidity and mortality and healthcare costs. The objective of this review is to synthesize recent knowledge and evidence available regarding post sepsis syndrome.
Method: a narrative review of articles published between 2000 and 2023 in PubMed, Sciencedirect, and LILACS was conducted. The MeSH terms "Sepsis," "Post ICU syndrome," and "Post sepsis syndrome" were used. A total of 221 articles were identified; 84 met inclusion criteria and were analyzed to describe the clinical and pathophysiological manifestations and impact of post sepsis syndrome.
Development: the available evidence shows that sepsis survivors present persistent impairment in physical, cognitive, and psychological domains. The syndrome is associated with prolonged immune dysfunction, frequent rehospitalizations, decreased functional autonomy, and increased cardiovascular and neuropsychiatric risk. High mortality rates up to five years after the event and high socioeconomic costs have also been documented. No standardized follow-up protocols or uniform rehabilitation strategies were identified in the reviewed literature.
Conclusions: post sepsis syndrome is an underestimated and underdiagnosed problem that represents a clinical and public health challenge. Large-scale studies are needed to define its true epidemiological burden and guide the implementation of multidisciplinary follow-up and rehabilitation programs to reduce its impact on patient survival and quality of life.
References
1. Mostel, Z., Perl, A., Marck, M. et al. Post-sepsis syndrome – an evolving entity that afflicts survivors of sepsis. Mol Med 26, 6 (2020). https://doi.org/10.1186/s10020-019-0132-z DOI: https://doi.org/10.1186/s10020-019-0132-z
2. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644. DOI: https://doi.org/10.1378/chest.101.6.1644
3. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B. DOI: https://doi.org/10.1097/01.CCM.0000050454.01978.3B
4. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. DOI: https://doi.org/10.1001/jama.2016.0287
5. Foster, S., Hargreaves, D. & Medzhitov, R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447, 972–978 (2007). https://doi.org/10.1038/nature05836. DOI: https://doi.org/10.1038/nature05836
6. Wen H, Dou Y, Hogaboam CM, Kunkel SL. Epigenetic regulation of dendritic cell-derived interleukin-12 facilitates immunosuppression after a severe innate immune response. Blood. 2008 Feb 15;111(4):1797-804. doi: 10.1182/blood-2007-08-106443. Epub 2007 Nov 30. PMID: 18055863 DOI: https://doi.org/10.1182/blood-2007-08-106443
7. El Gazzar M, Yoza BK, Chen X, Garcia BA, Young NL, McCall CE. Chromatin-specific remodeling by HMGB1 and linker histone H1 silences proinflammatory genes during endotoxin tolerance. Mol Cell Biol. 2009 Apr;29(7):1959-71. doi: 10.1128/MCB.01862-08. Epub 2009 Jan 21. PMID: 19158276. DOI: https://doi.org/10.1128/MCB.01862-08
8. Carson WF 4th, Cavassani KA, Ito T, Schaller M, Ishii M, Dou Y, Kunkel SL. Impaired CD4+ T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis. Eur J Immunol. 2010 Apr;40(4):998-1010. doi: 10.1002/eji.200939739. DOI: https://doi.org/10.1002/eji.200939739
9. Davis FM, Schaller MA, Dendekker A, Joshi AD, Kimball AS, Evanoff H, Wilke C, Obi AT, Melvin WJ, Cavassani K, Scola M, Carson B, Moser S, Blanc V, Engoren M, Moore BB, Kunkel SL, Gallagher KA. Sepsis Induces Prolonged Epigenetic Modifications in Bone Marrow and Peripheral Macrophages Impairing Inflammation and Wound Healing. Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2353-2366. doi: 10.1161/ATVBAHA.119.312754. DOI: https://doi.org/10.1161/ATVBAHA.119.312754
10. Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011 Dec 21;306(23):2594-605. doi: 10.1001/jama.2011.1829.
11. Ammer-Herrmenau C, Kulkarni U, Andreas N, Ungelenk M, Ravens S, Hübner C, Kather A, Kurth I, Bauer M, Kamradt T. Sepsis induces long-lasting impairments in CD4+ T-cell responses despite rapid numerical recovery of T-lymphocyte populations. PLoS One. 2019 Feb 7;14(2):e0211716. doi: 10.1371/journal.pone.0211716. DOI: https://doi.org/10.1371/journal.pone.0211716
12. Arens C, Bajwa SA, Koch C, Siegler BH, Schneck E, Hecker A, Weiterer S, Lichtenstern C, Weigand MA, Uhle F. Sepsis-induced long-term immune paralysis--results of a descriptive, explorative study. Crit Care. 2016 Feb 29;20:93. doi: 10.1186/s13054-016-1233-5.
13. Mathias B, Delmas AL, Ozrazgat-Baslanti T, Vanzant EL, Szpila BE, Mohr AM, Moore FA, Brakenridge SC, Brumback BA, Moldawer LL, Efron PA; the Sepsis, Critical Illness Research Center Investigators. Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock. Ann Surg. 2017 Apr;265(4):827-834. doi: 10.1097/SLA.0000000000001783. DOI: https://doi.org/10.1097/SLA.0000000000001783
14. Scicluna BP, van Vught LA, Zwinderman AH, Wiewel MA, Davenport EE, Burnham KL, Nürnberg P, Schultz MJ, Horn J, Cremer OL, Bonten MJ, Hinds CJ, Wong HR, Knight JC, van der Poll T; MARS consortium. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med. 2017 Oct;5(10):816-826. doi: 10.1016/S2213-2600(17)30294-1. DOI: https://doi.org/10.1016/S2213-2600(17)30294-1
15. Gritte RB, Souza-Siqueira T, Curi R, Machado MCC, Soriano FG. Why Septic Patients Remain Sick After Hospital Discharge? Front Immunol. 2021 Feb 15;11:605666. doi: 10.3389/fimmu.2020.605666. PMID: 33658992. DOI: https://doi.org/10.3389/fimmu.2020.605666
16. Kawakami D, Fujitani S, Morimoto T, Dote H, Takita M, Takaba A, Hino M, Nakamura M, Irie H, Adachi T, Shibata M, Kataoka J, Korenaga A, Yamashita T, Okazaki T, Okumura M, Tsunemitsu T. Prevalence of post-intensive care syndrome among Japanese intensive care unit patients: a prospective, multicenter, observational J-PICS study. Crit Care. 2021 Feb 16;25(1):69. doi: 10.1186/s13054-021-03501-z. PMID: 33593406. DOI: https://doi.org/10.1186/s13054-021-03501-z
17. Huang CY, Daniels R, Lembo A, Hartog C, O’Brien J, Heymann T, et al. Life after sepsis: An international survey of survivors to understand the post-sepsis syndrome. International Journal for Quality in Health Care. 2019;31(3).
18. Huang CY, Daniels R, Lembo A, Hartog C, O'Brien J, Heymann T, Reinhart K, Nguyen HB; Sepsis Survivors Engagement Project (SSEP). Life after sepsis: an international survey of survivors to understand the post-sepsis syndrome. Int J Qual Health Care. 2019 Apr 1;31(3):191-198. doi: 10.1093/intqhc/mzy137. DOI: https://doi.org/10.1093/intqhc/mzy137
19. Inoue S, Nakanishi N, Sugiyama J, Moriyama N, Miyazaki Y, Sugimoto T, Fujinami Y, Ono Y, Kotani J. Prevalence and Long-Term Prognosis of Post-Intensive Care Syndrome after Sepsis: A Single-Center Prospective Observational Study. J Clin Med. 2022 Sep 6;11(18):5257. doi: 10.3390/jcm11185257. DOI: https://doi.org/10.3390/jcm11185257
20. Montuclard L, Garrouste-Orgeas M, Timsit JF, Misset B, De Jonghe B, Carlet J. Outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay. Crit Care Med. 2000 Oct;28(10):3389-95. doi: 10.1097/00003246-200010000-00002. DOI: https://doi.org/10.1097/00003246-200010000-00002
21. María Eugenia Niño Mantilla, Diego Torres Dueñas, María Eugenia Cárdenas Angelone, Andrea Paola Godoy DíaNataly Moreno Díaz, Vivian Sanabria Pinillos, Ana María Ospina Galeano, et al. Factores pronósticos de mortalidad por sepsis severa en unidadesde cuidado crítico del área metropolitana de Bucaramanga -Association between prognosis factorsand mortality in Bucaramanga [Internet]. Bucaramanga; 2012 Apr [cited 2023 Nov 11]. Available from: https://revistas.unab.edu.co/index.php/medunab/article/view/1586 DOI: https://doi.org/10.29375/01237047.1586
22. Rimachi R, Vincent JL, Brimioulle S. Survival and quality of life after prolonged intensive care unit stay. Anaesth Intensive Care. 2007 Feb;35(1):62-7. doi: 10.1177/0310057X0703500108. DOI: https://doi.org/10.1177/0310057X0703500108
23. Quartin AA, Schein RM, Kett DH, Peduzzi PN. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997 Apr 2;277(13):1058-63. DOI: https://doi.org/10.1001/jama.1997.03540370048035
24. Korosec Jagodic H, Jagodic K, Podbregar M. Long-term outcome and quality of life of patients treated in surgical intensive care: a comparison between sepsis and trauma. Crit Care. 2006;10(5):R134. doi: 10.1186/cc5047. DOI: https://doi.org/10.1186/cc5047
25. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553. DOI: https://doi.org/10.1001/jama.2010.1553
26. Conde KA, Silva E, Silva CO, Ferreira E, Freitas FG, Castro I, Rea-Neto A, Grion CM, Moura AD, Lobo SM, Azevedo LC, Machado FR. Differences in sepsis treatment and outcomes between public and private hospitals in Brazil: a multicenter observational study. PLoS One. 2013 Jun 6;8(6):e64790. doi: 10.1371/journal.pone.0064790. DOI: https://doi.org/10.1371/journal.pone.0064790
27. Burchardi H, Schneider H. Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost effectiveness of therapy. Pharmacoeconomics. 2004;22(12):793-813. doi: 10.2165/00019053-200422120-00003. DOI: https://doi.org/10.2165/00019053-200422120-00003
28. Paoli CJ, Reynolds MA, Sinha M, Gitlin M, Crouser E. Epidemiology and Costs of Sepsis in the United States-An Analysis Based on Timing of Diagnosis and Severity Level. Crit Care Med. 2018 Dec;46(12):1889-1897. doi: 10.1097/CCM.0000000000003342. DOI: https://doi.org/10.1097/CCM.0000000000003342
29. Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. DOI: https://doi.org/10.1016/S0140-6736(18)30696-2
30. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. DOI: https://doi.org/10.1056/NEJMra1208623
31. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Møller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. DOI: https://doi.org/10.1007/s00134-021-06506-y
32. Preiser JC, van Zanten AR, Berger MM, Biolo G, Casaer MP, Doig GS, Griffiths RD, Heyland DK, Hiesmayr M, Iapichino G, Laviano A, Pichard C, Singer P, Van den Berghe G, Wernerman J, Wischmeyer P, Vincent JL. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care. 2015 Jan 29;19(1):35. doi: 10.1186/s13054-015-0737-8. DOI: https://doi.org/10.1186/s13054-015-0737-8
33. De Waele E, Malbrain MLNG, Spapen H. Nutrition in Sepsis: A Bench-to-Bedside Review. Nutrients. 2020 Feb 2;12(2):395. doi: 10.3390/nu12020395. DOI: https://doi.org/10.3390/nu12020395
34. Marik PE, Hooper MH. Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. Intensive Care Med. 2016 Mar;42(3):316-323. doi: 10.1007/s00134-015-4131-4. DOI: https://doi.org/10.1007/s00134-015-4131-4
35. van der Slikke EC, Star BS, van Meurs M, Henning RH, Moser J, Bouma HR. Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI. Crit Care. 2021 Jan 25;25(1):36. doi: 10.1186/s13054-020-03424-1. DOI: https://doi.org/10.1186/s13054-020-03424-1
36. Singer M. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence. 2014 Jan 1;5(1):66-72. doi: 10.4161/viru.26907. DOI: https://doi.org/10.4161/viru.26907
37. van der Slikke EC, Star BS, Quinten VM, Ter Maaten JC, Ligtenberg JJM, van Meurs M, Gansevoort RT, Bakker SJL, Chao MR, Henning RH, Bouma HR. Association between oxidized nucleobases and mitochondrial DNA damage with long-term mortality in patients with sepsis. Free Radic Biol Med. 2022 Feb 1;179:156-163. doi: 10.1016/j.freeradbiomed.2021.12.305. DOI: https://doi.org/10.1016/j.freeradbiomed.2021.12.305
38. Haden DW, Suliman HB, Carraway MS, Welty-Wolf KE, Ali AS, Shitara H, Yonekawa H, Piantadosi CA. Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis. Am J Respir Crit Care Med. 2007 Oct 15;176(8):768-77. doi: 10.1164/rccm.200701-161OC. DOI: https://doi.org/10.1164/rccm.200701-161OC
39. Lowes DA, Thottakam BM, Webster NR, Murphy MP, Galley HF. The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis. Free Radic Biol Med. 2008 Dec 1;45(11):1559-65. doi: 10.1016/j.freeradbiomed.2008.09.003. DOI: https://doi.org/10.1016/j.freeradbiomed.2008.09.003
40. Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018 Feb;14(2):121-137. doi: 10.1038/nrneph.2017.165. DOI: https://doi.org/10.1038/nrneph.2017.165
41. Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011 Dec 21;306(23):2594-605. doi: 10.1001/jama.2011.1829. DOI: https://doi.org/10.1001/jama.2011.1829
42. Arens C, Bajwa SA, Koch C, Siegler BH, Schneck E, Hecker A, Weiterer S, Lichtenstern C, Weigand MA, Uhle F. Sepsis-induced long-term immune paralysis--results of a descriptive, explorative study. Crit Care. 2016 Feb 29;20:93. doi: 10.1186/s13054-016-1233-5. DOI: https://doi.org/10.1186/s13054-016-1233-5
43. Davies R, O'Dea K, Gordon A. Immune therapy in sepsis: Are we ready to try again? J Intensive Care Soc. 2018 Nov;19(4):326-344. doi: 10.1177/1751143718765407. DOI: https://doi.org/10.1177/1751143718765407
44. Sjöberg M, Eriksson M. Hand disinfectant practice: the impact of an education intervention. Open Nurs J. 2010 Feb 23;4:20-4. doi: 10.2174/1874434601004010020. DOI: https://doi.org/10.2174/1874434601004010020
45. Schlapbach LJ, Kissoon N, Alhawsawi A, Aljuaid MH, Daniels R, Gorordo-Delsol LA, Machado F, Malik I, Nsutebu EF, Finfer S, Reinhart K. World Sepsis Day: a global agenda to target a leading cause of morbidity and mortality. Am J Physiol Lung Cell Mol Physiol. 2020 Sep 1;319(3):L518-L522. doi: 10.1152/ajplung.00369.2020. DOI: https://doi.org/10.1152/ajplung.00369.2020
46. Zheng C, Shao W, Chen X, Zhang B, Wang G, Zhang W. Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis. Int J Infect Dis. 2022 Jan;114:252-260. doi: 10.1016/j.ijid.2021.11.009. DOI: https://doi.org/10.1016/j.ijid.2021.11.009
47. Parsons Leigh J, Brundin-Mather R, Moss SJ, Nickel A, Parolini A, Walsh D, Bigham BL, Carter AJE, Fox-Robichaud A, Fiest KM. Public awareness and knowledge of sepsis: a cross-sectional survey of adults in Canada. Crit Care. 2022 Nov 3;26(1):337. doi: 10.1186/s13054-022-04215-6 DOI: https://doi.org/10.1186/s13054-022-04215-6
48. Vincent JL. Increasing awareness of sepsis: World Sepsis Day. Crit Care. 2012 Sep 13;16(5):152. doi: 10.1186/cc11511. DOI: https://doi.org/10.1186/cc11511
49. Jabaley CS, Blum JM, Groff RF, O'Reilly-Shah VN. Global trends in the awareness of sepsis: insights from search engine data between 2012 and 2017. Crit Care. 2018 Jan 17;22(1):7. doi: 10.1186/s13054-017-1914-8. DOI: https://doi.org/10.1186/s13054-017-1914-8
50. Farsi D, Martinez-Menchaca HR, Ahmed M, Farsi N. Social Media and Health Care (Part II): Narrative Review of Social Media Use by Patients. J Med Internet Res. 2022 Jan 7;24(1):e30379. doi: 10.2196/30379. DOI: https://doi.org/10.2196/30379
51. Lee CF, Cowling BJ, Feng S, Aso H, Wu P, Fukuda K, Seto WH. Impact of antibiotic stewardship programmes in Asia: a systematic review and meta-analysis. J Antimicrob Chemother. 2018 Apr 1;73(4):844-851. doi: 10.1093/jac/dkx492. DOI: https://doi.org/10.1093/jac/dkx492
52. Schuts EC, Hulscher MEJL, Mouton JW, Verduin CM, Stuart JWTC, Overdiek HWPM, van der Linden PD, Natsch S, Hertogh CMPM, Wolfs TFW, Schouten JA, Kullberg BJ, Prins JM. Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis. Lancet Infect Dis. 2016 Jul;16(7):847-856. doi: 10.1016/S1473-3099(16)00065-7. DOI: https://doi.org/10.1016/S1473-3099(16)00065-7
53. Apitzsch S, Larsson L, Larsson AK, Linder A. The physical and mental impact of surviving sepsis - a qualitative study of experiences and perceptions among a Swedish sample. Arch Public Health. 2021 May 1;79(1):66. doi: 10.1186/s13690-021-00585-5. DOI: https://doi.org/10.1186/s13690-021-00585-5
54. Stallmach A, Kesselmeier M, Bauer M, Gramlich J, Finke K, Fischer A, Fleischmann-Struzek C, Heutelbeck A, Katzer K, Mutschke S, Pletz MW, Quickert S, Reinhart K, Stallmach Z, Walter M, Scherag A, Reuken PA. Comparison of fatigue, cognitive dysfunction and psychological disorders in post-COVID patients and patients after sepsis: is there a specific constellation? Infection. 2022 Jun;50(3):661-669. doi: 10.1007/s15010-021-01733-3. DOI: https://doi.org/10.1007/s15010-021-01733-3
55. Hund E. Neurological complications of sepsis: critical illness polyneuropathy and myopathy. J Neurol. 2001 Nov;248(11):929-34. doi: 10.1007/s004150170043. DOI: https://doi.org/10.1007/s004150170043
56. Sasegbon A, O'Shea L, Hamdy S. Examining the relationship between sepsis and oropharyngeal dysphagia in hospitalised elderly patients: a retrospective cohort study. Frontline Gastroenterol. 2018 Oct;9(4):256-261. doi: 10.1136/flgastro-2018-100994. DOI: https://doi.org/10.1136/flgastro-2018-100994
57. Zuercher P, Moret CS, Dziewas R, Schefold JC. Dysphagia in the intensive care unit: epidemiology, mechanisms, and clinical management. Crit Care. 2019 Mar 28;23(1):103. doi: 10.1186/s13054-019-2400-2. DOI: https://doi.org/10.1186/s13054-019-2400-2
58. Goldsmith T. Evaluation and treatment of swallowing disorders following endotracheal intubation and tracheostomy. Int Anesthesiol Clin. 2000 Summer;38(3):219-42. doi: 10.1097/00004311-200007000-00013. DOI: https://doi.org/10.1097/00004311-200007000-00013
59. Fredriksson K, Hammarqvist F, Strigård K, Hultenby K, Ljungqvist O, Wernerman J, Rooyackers O. Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1044-50. doi: 10.1152/ajpendo.00218.2006. DOI: https://doi.org/10.1152/ajpendo.00218.2006
60. Long CL, Schiller WR, Blakemore WS, Geiger JW, O'Dell M, Henderson K. Muscle protein catabolism in the septic patient as measured by 3-methylhistidine excretion. Am J Clin Nutr. 1977 Aug;30(8):1349-52. doi: 10.1093/ajcn/30.8.1349. DOI: https://doi.org/10.1093/ajcn/30.8.1349
61. Baggerman MR, van Dijk DPJ, Winkens B, van Gassel RJJ, Bol ME, Schnabel RM, Bakers FC, Olde Damink SWM, van de Poll MCG. Muscle wasting associated co-morbidities, rather than sarcopenia are risk factors for hospital mortality in critical illness. J Crit Care. 2020 Apr;56:31-36. doi: 10.1016/j.jcrc.2019.11.016. DOI: https://doi.org/10.1016/j.jcrc.2019.11.016
62. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481. DOI: https://doi.org/10.1001/jama.2013.278481
63. Mankowski RT, Anton SD, Ghita GL, Brumback B, Cox MC, Mohr AM, Leeuwenburgh C, Moldawer LL, Efron PA, Brakenridge SC, Moore FA. Older Sepsis Survivors Suffer Persistent Disability Burden and Poor Long-Term Survival. J Am Geriatr Soc. 2020 Sep;68(9):1962-1969. doi: 10.1111/jgs.16435. DOI: https://doi.org/10.1111/jgs.16435
64. Herridge MS, Azoulay É. Outcomes after Critical Illness. N Engl J Med. 2023 Mar 9;388(10):913-924. doi: 10.1056/NEJMra2104669. DOI: https://doi.org/10.1056/NEJMra2104669
65. Mankowski RT, Anton SD, Ghita GL, Brumback B, Darden DB, Bihorac A, Leeuwenburgh C, Moldawer LL, Efron PA, Brakenridge SC, Moore FA. Older Adults Demonstrate Biomarker Evidence of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) After Sepsis. J Gerontol A Biol Sci Med Sci. 2022 Jan 7;77(1):188-196. doi: 10.1093/gerona/glab080. DOI: https://doi.org/10.1093/gerona/glab080
66. Mankowski RT, Laitano O, Darden D, Kelly L, Munley J, Loftus TJ, Mohr AM, Efron PA, Thomas RM. Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets. Shock. 2022 Jan 1;57(1):15-23. doi: 10.1097/SHK.0000000000001843. DOI: https://doi.org/10.1097/SHK.0000000000001843
67. Schmitt RE, Dasgupta A, Arneson-Wissink PC, Datta S, Ducharme AM, Doles JD. Muscle stem cells contribute to long-term tissue repletion following surgical sepsis. J Cachexia Sarcopenia Muscle. 2023 Jun;14(3):1424-1440. doi: 10.1002/jcsm.13214. DOI: https://doi.org/10.1002/jcsm.13214
68. Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS, Espeland MA, Fielding RA, Gill TM, Groessl EJ, King AC, Kritchevsky SB, Manini TM, McDermott MM, Miller ME, Newman AB, Rejeski WJ, Sink KM, Williamson JD; LIFE study investigators. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA. 2014 Jun 18;311(23):2387-96. doi: 10.1001/jama.2014.5616. DOI: https://doi.org/10.1001/jama.2014.5616
69. Fuke R, Hifumi T, Kondo Y, Hatakeyama J, Takei T, Yamakawa K, Inoue S, Nishida O. Early rehabilitation to prevent postintensive care syndrome in patients with critical illness: a systematic review and meta-analysis. BMJ Open. 2018 May 5;8(5):e019998. doi: 10.1136/bmjopen-2017-019998. DOI: https://doi.org/10.1136/bmjopen-2017-019998
70. Nakanishi N, Oto J, Tsutsumi R, Yamamoto T, Ueno Y, Nakataki E, Itagaki T, Sakaue H, Nishimura M. Effect of Electrical Muscle Stimulation on Upper and Lower Limb Muscles in Critically Ill Patients: A Two-Center Randomized Controlled Trial. Crit Care Med. 2020 Nov;48(11):e997-e1003. doi: 10.1097/CCM.0000000000004522. DOI: https://doi.org/10.1097/CCM.0000000000004522
71. Grunow, J.J., Goll, M., Carbon, N.M. et al. Differential contractile response of critically ill patients to neuromuscular electrical stimulation. Crit Care 23, 308 (2019). https://doi.org/10.1186/s13054-019-2540-4 DOI: https://doi.org/10.1186/s13054-019-2540-4
72. Medrinal C, Combret Y, Prieur G, Robledo Quesada A, Bonnevie T, Gravier FE, Dupuis Lozeron E, Frenoy E, Contal O, Lamia B. Comparison of exercise intensity during four early rehabilitation techniques in sedated and ventilated patients in ICU: a randomised cross-over trial. Crit Care. 2018 Apr 27;22(1):110. doi: 10.1186/s13054-018-2030-0. DOI: https://doi.org/10.1186/s13054-018-2030-0
73. Verceles AC, Serra M, Davis D, Alon G, Wells CL, Parker E, Sorkin J, Bhatti W, Terrin ML. Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness-The ExPrES study. Heart Lung. 2023 Mar-Apr;58:229-235. doi: 10.1016/j.hrtlng.2022.11.013. DOI: https://doi.org/10.1016/j.hrtlng.2022.11.013
74. Mira JC, Gentile LF, Mathias BJ, Efron PA, Brakenridge SC, Mohr AM, Moore FA, Moldawer LL. Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome. Crit Care Med. 2017 Feb;45(2):253-262. doi: 10.1097/CCM.0000000000002074. DOI: https://doi.org/10.1097/CCM.0000000000002074
75. Beesley SJ, Weber G, Sarge T, Nikravan S, Grissom CK, Lanspa MJ, Shahul S, Brown SM. Septic Cardiomyopathy. Crit Care Med. 2018 Apr;46(4):625-634. doi: 10.1097/CCM.0000000000002851. DOI: https://doi.org/10.1097/CCM.0000000000002851
76. Kosyakovsky LB, Angriman F, Katz E, Adhikari NK, Godoy LC, Marshall JC, Ferreyro BL, Lee DS, Rosenson RS, Sattar N, Verma S, Toma A, Englesakis M, Burstein B, Farkouh ME, Herridge M, Ko DT, Scales DC, Detsky ME, Bibas L, Lawler PR. Association between sepsis survivorship and long-term cardiovascular outcomes in adults: a systematic review and meta-analysis. Intensive Care Med. 2021 Sep;47(9):931-942. doi: 10.1007/s00134-021-06479-y. DOI: https://doi.org/10.1007/s00134-021-06479-y
77. Jentzer JC, Lawler PR, Van Houten HK, Yao X, Kashani KB, Dunlay SM. Cardiovascular Events Among Survivors of Sepsis Hospitalization: A Retrospective Cohort Analysis. J Am Heart Assoc. 2023 Feb 7;12(3):e027813. doi: 10.1161/JAHA.122.027813. DOI: https://doi.org/10.1161/JAHA.122.027813
78. Angriman F, Rosella LC, Lawler PR, Ko DT, Wunsch H, Scales DC. Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study. Intensive Care Med. 2022 Apr;48(4):448-457. doi: 10.1007/s00134-022-06634-z. DOI: https://doi.org/10.1007/s00134-022-06634-z
79. Walkey AJ, Wiener RS, Ghobrial JM, Curtis LH, Benjamin EJ. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA. 2011 Nov 23;306(20):2248-54. doi: 10.1001/jama.2011.1615. DOI: https://doi.org/10.1001/jama.2011.1615
80. Induruwa I, Hennebry E, Hennebry J, Thakur M, Warburton EA, Khadjooi K. Sepsis-driven atrial fibrillation and ischaemic stroke. Is there enough evidence to recommend anticoagulation? Eur J Intern Med. 2022 Apr;98:32-36. doi: 10.1016/j.ejim.2021.10.022. DOI: https://doi.org/10.1016/j.ejim.2021.10.022
81. Li Y, Ji M, Yang J. Current Understanding of Long-Term Cognitive Impairment After Sepsis. Front Immunol. 2022 May 6;13:855006. doi: 10.3389/fimmu.2022.855006. DOI: https://doi.org/10.3389/fimmu.2022.855006
82. Liu V, Lei X, Prescott HC, Kipnis P, Iwashyna TJ, Escobar GJ. Hospital readmission and healthcare utilization following sepsis in community settings. J Hosp Med. 2014 Aug;9(8):502-7. doi: 10.1002/jhm.2197. DOI: https://doi.org/10.1002/jhm.2197
83. Cereuil A, Ronflé R, Culver A, Boucekine M, Papazian L, Lefebvre L, Leone M. Septic Shock: Phenotypes and Outcomes. Adv Ther. 2022 Nov;39(11):5058-5071. doi: 10.1007/s12325-022-02280-5. DOI: https://doi.org/10.1007/s12325-022-02280-5
84. Seymour CW, Kennedy JN, Wang S, Chang CH, Elliott CF, Xu Z, Berry S, Clermont G, Cooper G, Gomez H, Huang DT, Kellum JA, Mi Q, Opal SM, Talisa V, van der Poll T, Visweswaran S, Vodovotz Y, Weiss JC, Yealy DM, Yende S, Angus DC. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA. 2019 May 28;321(20):2003-2017. doi: 10.1001/jama.2019.5791. DOI: https://doi.org/10.1001/jama.2019.5791
85. Mora-Martínez, S.; Montoya-Quintero, K. F. Fluidoterapia Reflexiva: Desde La fisiología a La práctica clínica. Rev Colomb Cir 2024, 39, 764-778. DOI: https://doi.org/10.30944/20117582.2468
86. Berrío N, Sánchez JP, Mora S, Faley-García O, Fernando-Vieco G. Validación del cuestionario sobre depresión PHQ-9 en una muestra colombiana no clínica: Validation of the PHQ-9 depression questionnaire in a non-clinical Colombian sample. RPPC [Internet]. 26 de marzo de 2024 [citado 9 de septiembre de 2025];29(1):59-6. DOI: https://doi.org/10.5944/rppc.37748
87. Torres JSS et al. Sepsis and post-sepsis syndrome: a multisystem challenge requiring comprehensive care and management-a review. Front Med (Lausanne). 2025 Apr 8;12:1560737. DOI: https://doi.org/10.3389/fmed.2025.1560737
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