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Plasma biomarkers of inflammation, coagulation, and brain injury as predictors of delirium duration in older hospitalized patients


Autoři: J. Brennan McNeil aff001;  Christopher G. Hughes aff002;  Timothy Girard aff002;  Lorraine B. Ware aff001;  E. Wesley Ely aff001;  Rameela Chandrasekhar aff002;  Jin H. Han aff002
Působiště autorů: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff001;  The Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff002;  Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff003;  Clinical Research, Investigation, and Systems Modeling of Acute illness (CRISMA) Center in the Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America aff004;  Veteran Affairs Geriatric Research, Education, and Clinical Center (GRECC), Nashville, Tennessee, United States of America aff005;  Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff006;  Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff007
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226412

Souhrn

Background

Delirium's pathophysiology is poorly understood. We sought to determine if plasma biomarkers of inflammation, coagulation, endothelial activation, and blood brain barrier (BBB) injury were associated with emergency department (ED) delirium duration.

Methods

We enrolled hospitalized patients who were 65 years or older from the ED. Plasma biomarkers of inflammation (interleukin-6 [IL-6], IL-8, soluble tumor necrosis factor receptor I [sTNFRI]), coagulation (Protein C), endothelial activation (plasminogen activating inhibitor-1 [PAI-1]), and BBB injury (S100B) at were measured using blood obtained at enrollment. The dependent variable was ED delirium duration which was determined by the Brief Confusion Assessment Method assessed in the ED and hospitalization. Proportional odds logistic regression analyses were performed adjusted for relevant confounders and allowing for interaction by baseline dementia status.

Results

A total of 156 patients were enrolled. IL-6 (POR = 1.59, 95%CI: 1.09–2.32) and PAI-1 (POR = 2.96, 95%CI: 1.48 to 6.85) were independently associated with more prominent ED delirium duration in subjects without dementia only. No significant associations between IL-8, Protein C, sTNRFI, and S100B and ED delirium duration were observed.

Conclusions

Plasma Biomarkers of systemic inflammation and endothelial activation are associated with ED delirium duration in older ED patients without dementia.

Klíčová slova:

Biomarkers – Blood plasma – Brain damage – Central nervous system – Critical care and emergency medicine – Dementia – Inflammation – Pathogenesis


Zdroje

1. Hustey FM, Meldon SW, Smith MD, Lex CK. The effect of mental status screening on the care of elderly emergency department patients. Annals of emergency medicine. 2003;41(5):678–84. doi: 10.1067/mem.2003.152 12712035.

2. Han JH, Zimmerman EE, Cutler N, Schnelle J, Morandi A, Dittus RS, et al. Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med. 2009;16(3):193–200. doi: 10.1111/j.1553-2712.2008.00339.x 19154565.

3. Elie M, Rousseau F, Cole M, Primeau F, McCusker J, Bellavance F. Prevalence and detection of delirium in elderly emergency department patients. CMAJ. 2000;163(8):977–81. 11068569.

4. Kakuma R, du Fort GG, Arsenault L, Perrault A, Platt RW, Monette J, et al. Delirium in older emergency department patients discharged home: effect on survival. J Am Geriatr Soc. 2003;51(4):443–50. doi: 10.1046/j.1532-5415.2003.51151.x 12657062.

5. Han JH, Shintani A, Eden S, Morandi A, Solberg LM, Schnelle J, et al. Delirium in the emergency department: an independent predictor of death within 6 months. Annals of emergency medicine. 2010;56(3):244–52. doi: 10.1016/j.annemergmed.2010.03.003 20363527.

6. Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998;13(4):234–42. doi: 10.1046/j.1525-1497.1998.00073.x 9565386.

7. Levkoff SE, Evans DA, Liptzin B, Cleary PD, Lipsitz LA, Wetle TT, et al. Delirium. The occurrence and persistence of symptoms among elderly hospitalized patients. Arch Intern Med. 1992;152(2):334–40. doi: 10.1001/archinte.152.2.334 1739363.

8. Francis J, Martin D, Kapoor WN. A prospective study of delirium in hospitalized elderly. JAMA. 1990;263(8):1097–101. 2299782.

9. Pompei P, Foreman M, Cassel CK, Alessi C, Cox D. Detecting delirium among hospitalized older patients. Arch Intern Med. 1995;155(3):301–7. 7832602.

10. O'Keeffe S, Lavan J. The prognostic significance of delirium in older hospital patients. J Am Geriatr Soc. 1997;45(2):174–8. doi: 10.1111/j.1532-5415.1997.tb04503.x 9033515.

11. Pitkala KH, Laurila JV, Strandberg TE, Tilvis RS. Prognostic significance of delirium in frail older people. Dementia and geriatric cognitive disorders. 2005;19(2–3):158–63. doi: 10.1159/000082888 15627764.

12. Han JH, Vasilevskis EE, Chandrasekhar R, Liu X, Schnelle JF, Dittus RS, et al. Delirium in the Emergency Department and Its Extension into Hospitalization (DELINEATE) Study: Effect on 6-month Function and Cognition. J Am Geriatr Soc. 2017;65(6):1333–8. doi: 10.1111/jgs.14824 28263444; PubMed Central PMCID: PMC5478452.

13. McCusker J, Cole M, Dendukuri N, Han L, Belzile E. The course of delirium in older medical inpatients: a prospective study. J Gen Intern Med. 2003;18(9):696–704. doi: 10.1046/j.1525-1497.2003.20602.x 12950477.

14. Gonzalez M, Martinez G, Calderon J, Villarroel L, Yuri F, Rojas C, et al. Impact of delirium on short-term mortality in elderly inpatients: a prospective cohort study. Psychosomatics. 2009;50(3):234–8. Epub 2009/07/02. 50/3/234 [pii] doi: 10.1176/appi.psy.50.3.234 19567762.

15. AGS/NIA Delirium Conference Writing Group PC, Faculty. The American Geriatrics Society/National Institute on Aging Bedside-to-Bench Conference: Research Agenda on Delirium in Older Adults. J Am Geriatr Soc. 2015;63(5):843–52. doi: 10.1111/jgs.13406 25834932.

16. Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry. 2013;21(12):1190–222. doi: 10.1016/j.jagp.2013.09.005 24206937.

17. Downing JE, Miyan JA. Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease. Immunology today. 2000;21(6):281–9. doi: 10.1016/s0167-5699(00)01635-2 10825740.

18. Ait-Oufella H, Maury E, Lehoux S, Guidet B, Offenstadt G. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive care medicine. 2010;36(8):1286–98. doi: 10.1007/s00134-010-1893-6 20443110.

19. Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003;101(10):3765–77. doi: 10.1182/blood-2002-06-1887 12543869.

20. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nature reviews Neuroscience. 2006;7(1):41–53. doi: 10.1038/nrn1824 16371949.

21. Gavins F, Yilmaz G, Granger DN. The evolving paradigm for blood cell-endothelial cell interactions in the cerebral microcirculation. Microcirculation. 2007;14(7):667–81. doi: 10.1080/10739680701404903 17885993.

22. Taccone FS, Su F, Pierrakos C, He X, James S, Dewitte O, et al. Cerebral microcirculation is impaired during sepsis: an experimental study. Critical care. 2010;14(4):R140. doi: 10.1186/cc9205 20667108; PubMed Central PMCID: PMC2945121.

23. Vogel C, Bauer A, Wiesnet M, Preissner KT, Schaper W, Marti HH, et al. Flt-1, but not Flk-1 mediates hyperpermeability through activation of the PI3-K/Akt pathway. Journal of cellular physiology. 2007;212(1):236–43. doi: 10.1002/jcp.21022 17311300.

24. Vajtr D, Benada O, Kukacka J, Prusa R, Houstava L, Toupalik P, et al. Correlation of ultrastructural changes of endothelial cells and astrocytes occurring during blood brain barrier damage after traumatic brain injury with biochemical markers of BBB leakage and inflammatory response. Physiological research / Academia Scientiarum Bohemoslovaca. 2009;58(2):263–8. 18380546.

25. Hughes CG, Pandharipande PP, Thompson JL, Chandrasekhar R, Ware LB, Ely EW, et al. Endothelial Activation and Blood-Brain Barrier Injury as Risk Factors for Delirium in Critically Ill Patients. Critical care medicine. 2016;44(9):e809–17. doi: 10.1097/CCM.0000000000001739 27088157; PubMed Central PMCID: PMC4987204.

26. Girard TD, Ware LB, Bernard GR, Pandharipande PP, Thompson JL, Shintani AK, et al. Associations of markers of inflammation and coagulation with delirium during critical illness. Intensive care medicine. 2012;38(12):1965–73. doi: 10.1007/s00134-012-2678-x 22903241; PubMed Central PMCID: PMC3606929.

27. de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. Journal of psychosomatic research. 2007;62(5):521–5. doi: 10.1016/j.jpsychores.2006.11.013 17467406.

28. Adamis D, Lunn M, Martin FC, Treloar A, Gregson N, Hamilton G, et al. Cytokines and IGF-I in delirious and non-delirious acutely ill older medical inpatients. Age and ageing. 2009;38(3):326–32; discussion 251. doi: 10.1093/ageing/afp014 19269948.

29. van Munster BC, Bisschop PH, Zwinderman AH, Korevaar JC, Endert E, Wiersinga WJ, et al. Cortisol, interleukins and S100B in delirium in the elderly. Brain and cognition. 2010;74(1):18–23. doi: 10.1016/j.bandc.2010.05.010 20580479.

30. van Munster BC, Korevaar JC, Korse CM, Bonfrer JM, Zwinderman AH, de Rooij SE. Serum S100B in elderly patients with and without delirium. Int J Geriatr Psychiatry. 2010;25(3):234–9. Epub 2009/07/04. doi: 10.1002/gps.2326 19575407.

31. Plaschke K, Fichtenkamm P, Schramm C, Hauth S, Martin E, Verch M, et al. Early postoperative delirium after open-heart cardiac surgery is associated with decreased bispectral EEG and increased cortisol and interleukin-6. Intensive care medicine. 2010;36(12):2081–9. doi: 10.1007/s00134-010-2004-4 20689917.

32. van Munster BC, Korevaar JC, Zwinderman AH, Levi M, Wiersinga WJ, De Rooij SE. Time-course of cytokines during delirium in elderly patients with hip fractures. J Am Geriatr Soc. 2008;56(9):1704–9. doi: 10.1111/j.1532-5415.2008.01851.x 18691278.

33. Hughes CG, Patel MB, Brummel NE, Thompson JL, McNeil JB, Pandharipande PP, et al. Relationships between markers of neurologic and endothelial injury during critical illness and long-term cognitive impairment and disability. Intensive care medicine. 2018;44(3):345–55. doi: 10.1007/s00134-018-5120-1 29523900; PubMed Central PMCID: PMC5870884.

34. Han JH, Wilson A, Graves AJ, Shintani A, Schnelle JF, Ely EW. A quick and easy delirium assessment for nonphysician research personnel. The American journal of emergency medicine. 2016;34(6):1031–6. doi: 10.1016/j.ajem.2016.02.069 27021131; PubMed Central PMCID: PMC4899095.

35. Han JH, Wilson A, Shintani A, Graves AJ, Schnelle JF, Dittus RS, et al. A quick and easy delirium assessment for non-physician research personnel. Acad Emerg Med. 2013;20(S1):S125–26.

36. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001;286(21):2703–10. doi: 10.1001/jama.286.21.2703 11730446.

37. Jorm AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. Psychological medicine. 1994;24(1):145–53. doi: 10.1017/s003329170002691x 8208879.

38. Murray SB, Bates DW, Ngo L, Ufberg JW, Shapiro NI. Charlson Index is associated with one-year mortality in emergency department patients with suspected infection. Acad Emerg Med. 2006;13(5):530–6. doi: 10.1197/j.aem.2005.11.084 16551775.

39. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Critical care medicine. 1985;13(10):818–29. Epub 1985/10/01. 3928249.

40. Egberts A, Wijnbeld EH, Fekkes D, van der Ploeg MA, Ziere G, Hooijkaas H, et al. Neopterin: a potential biomarker for delirium in elderly patients. Dementia and geriatric cognitive disorders. 2015;39(1–2):116–24. doi: 10.1159/000366410 25413160.

41. Beloosesky Y, Hendel D, Weiss A, Hershkovitz A, Grinblat J, Pirotsky A, et al. Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. The journals of gerontology Series A, Biological sciences and medical sciences. 2007;62(4):420–6. doi: 10.1093/gerona/62.4.420 17452737.

42. Ritter C, Tomasi CD, Dal-Pizzol F, Pinto BB, Dyson A, de Miranda AS, et al. Inflammation biomarkers and delirium in critically ill patients. Critical care. 2014;18(3):R106. doi: 10.1186/cc13887 24886875; PubMed Central PMCID: PMC4075116.

43. Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Critical care medicine. 2004;32(9):1825–31. doi: 10.1097/01.ccm.0000138558.16257.3f 15343008.

44. Alves JL. Blood-brain barrier and traumatic brain injury. J Neurosci Res. 2014;92(2):141–7. doi: 10.1002/jnr.23300 24327344.

45. 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):631–9. doi: 10.1097/ALN.0b013e31827bd193 23263016; PubMed Central PMCID: PMC3580006.

46. van Munster BC, Korse CM, de Rooij SE, Bonfrer JM, Zwinderman AH, Korevaar JC. Markers of cerebral damage during delirium in elderly patients with hip fracture. BMC neurology. 2009;9:21. Epub 2009/05/29. 1471-2377-9-21 [pii] doi: 10.1186/1471-2377-9-21 19473521; PubMed Central PMCID: PMC2695414.

47. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996;275(11):852–7. 8596223.


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