Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-30T05:56:16.907Z Has data issue: false hasContentIssue false
  • English
  • Français

Raised IL-2 and TNF-α concentrations are associated with postoperative delirium in patients undergoing coronary-artery bypass graft surgery

Published online by Cambridge University Press:  17 December 2013

Jakub Kazmierski ,
Andrzej Banys ,
Joanna Latek ,
Julius Bourke  and
Ryszard Jaszewski
Jakub Kazmierski*
Affiliation:
Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland
Andrzej Banys
Affiliation:
Department of Anaesthesiology and Intensive Cardiologic Care, 1st Chair of Cardiology and Cardiac Surgery, Medical University of Lodz, Lodz, Poland
Joanna Latek
Affiliation:
Central Veterans Hospital, Lodz, Poland
Julius Bourke
Affiliation:
The Centre for Psychiatry at The Wolfson Institute for Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Ryszard Jaszewski
Affiliation:
Department of Cardiac Surgery, 1st Chair of Cardiology and Cardiac Surgery, Medical University of Lodz, Lodz, Poland
*
Correspondence should be addressed to: Jakub Kazmierski, MD, PhD, Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland. Phone: +48 42 675 73 72; Fax: +48 42 675 77 29. Email: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

The knowledge base regarding the pathogenesis of postoperative delirium is limited. The primary aim of this study is to investigate whether increased levels of IL-2 and TNF-α are associated with delirium in patients who underwent coronary-artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). The secondary aim is to establish whether any association between raised cytokine levels and delirium is related to surgical and anesthetic procedures or mediated by pre-existing conditions associated with raised cytokine levels, such as major depressive disorder (MDD), cognitive impairment, or aging.

Methods:

Patients were examined and screened for MDD and cognitive impairment one day preoperatively, using the Mini International Neuropsychiatric Interview and The Montreal Cognitive Assessment and Trail Making Test Part B. Blood samples were collected postoperatively for cytokine levels.

Results:

Postoperative delirium screening was found positive in 36% (41 of 113) of patients. A multivariate logistic regression revealed that an increased concentration of pro-inflammatory cytokines is associated with delirium, and related to advancing age, preoperative cognitive decline of participants, and duration of CPB. According to receiver operating characteristic analysis, the most optimal cut-off for IL-2 and TNF-α concentrations in predicting the development of delirium were 907.5 U/ml and 10.95 pg/ml, respectively.

Conclusions:

The present study suggests that raised postoperative cytokine concentrations are associated with delirium after CABG surgery. Postoperative monitoring of pro-inflammatory markers combined with regular surveillance may be helpful in the early detection of postoperative delirium in this patient group.

Keywords

deliriumcoronary-artery bypass graftingcardiac surgerycytokinesinterleukins
Type
Research Article
Information
International Psychogeriatrics , Volume 26 , Issue 5 , May 2014 , pp. 845 - 855
Copyright
Copyright © International Psychogeriatric Association 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Brown, W. R., Moody, D. M., Challa, V. R., Stump, D. A. and Hammon, J. W. (2000). Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke, 31, 707–713.CrossRefGoogle ScholarPubMed
Bucerius, J. et al. (2004). Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. Journal of Thoracic and Cardiovascular Surgery, 127, 57–64.CrossRefGoogle ScholarPubMed
Cunningham, C. et al. (2009). Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biologic Psychiatry, 65, 304–312. doi:10.1016/j.biopsych.2008.07.024.CrossRefGoogle ScholarPubMed
de Rooij, S. E., van Munster, B. C., Korevaar, J. C. and Levi, M. (2007). Cytokines and acute phase response in delirium. Journal of Psychosomatic Research, 62, 521–525.CrossRefGoogle ScholarPubMed
Denicoff, K. D. et al. (1987). The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Annals of Internal Medicine, 107, 293–300.CrossRefGoogle ScholarPubMed
Detroyer, E., Dobbels, F., Verfaillie, E., Meyfroidt, G., Sergeant, P. and Milisen, K. (2008). Is preoperative anxiety and depression associated with onset of delirium after cardiac surgery in older patients? A prospective cohort study. Journal of the American Geriatric Society, 56, 2278–2284.CrossRefGoogle ScholarPubMed
Ely, E. W. et al. (2001). Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (CAM-ICU). Critical Care Medicine, 29, 1370–1379.CrossRefGoogle ScholarPubMed
Franceschi, C. et al. (2000). Inflamm-aging. An evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences, 908, 244–254.CrossRefGoogle ScholarPubMed
Franco, K., Litaker, D., Locala, J. and Bronson, D. (2001). The cost of delirium in the surgical patient. Psychosomatics, 42, 68–73.CrossRefGoogle ScholarPubMed
Girard, T. D., Pandharipande, P. P. and Ely, E. W. (2008). Delirium in the intensive care unit. Critical Care, 12 (Suppl. 3), S3. doi:10.1186/cc6149.CrossRefGoogle ScholarPubMed
Girard, T. D. et al. (2012). Associations of markers of inflammation and coagulation with delirium during critical illness. Intensive Care Medicine, 38, 1965–1973. doi:10.1007/s00134-012-2678-x.CrossRefGoogle Scholar
Hall, R. J., Shenkin, S. D. and Maclullich, A. M. (2011). A systematic literature review of cerebrospinal fluid biomarkers in delirium. Dementia and Geriatric Cognitive Disorders, 32, 79–93. doi:10.1159/000330757.Google Scholar
Huang, Z., Meola, D. and Petitto, J. M. (2012). Dissecting the effects of endogenous brain IL-2 and normal versus autoreactive T lymphocytes on microglial responsiveness and T cell trafficking in response to axonal injury. Neuroscience Letters, 526, 138–143. doi:10.1016/j.neulet.2012.08.018.CrossRefGoogle Scholar
Jiang, C. L. and Lu, C. L. (1998). Interleukin-2 and its effects in the central nervous system. Biological Signals and Receptors, 7, 148–156.CrossRefGoogle ScholarPubMed
Kazmierski, J., Banys, A., Latek, J., Bourke, J. and Jaszewski, R. (2013). Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study. Critical Care, 17, R38.CrossRefGoogle ScholarPubMed
Kazmierski, J. and Kloszewska, I. (2011). Is cortisol the key to the pathogenesis of delirium after coronary artery bypass graft surgery? Critical Care, 15, 102. doi:10.1186/cc9372.CrossRefGoogle Scholar
Kazmierski, J. et al. (2006). Preoperative predictors of delirium after cardiac surgery: a preliminary study. General Hospital Psychiatry, 28, 536–538.Google Scholar
Kazmierski, J. et al. IPDACS Study (2010a). Incidence and predictors of delirium after cardiac surgery: results from The IPDACS Study. Journal of Psychosomatic Research, 69, 179–185. doi:10.1016/j.jpsychores.2010.02.009.Google Scholar
Kazmierski, J. et al. (2010b). The use of DSM-IV and ICD-10 criteria and diagnostic scales for delirium among cardiac surgery patients: results from the IPDACS study. Journal of Neuropsychiatry and Clinical Neurosciences, 22, 426–432. doi:10.1176/appi.neuropsych.22.4.426.Google Scholar
Koster, S., Hensens, A. G., Schuurmans, M. J. and van der Palen, J. (2011). Risk factors of delirium after cardiac surgery: a systematic review. European Journal of Cardiovascular Nursing, 10, 197–204. Epub ahead of print, doi:10.1016/j.ejcnurse.2010.09.001.CrossRefGoogle ScholarPubMed
Kronfol, Z. and Remick, D. G. (2000). Cytokines and the brain: implications for clinical psychiatry. American Journal of Psychiatry, 157, 683–694.Google Scholar
Lee, H. B., DeLoatch, C. J., Cho, S., Rosenberg, P., Mears, S. C. and Sieber, F. E. (2008). Detection and management of pre-existing cognitive impairment and associated behavioral symptoms in the Intensive Care Unit. Critical Care Clinics, 24, 723–736. doi:10.1016/j.ccc.2008.05.006.Google Scholar
Lemstra, A. W., Kalisvaart, K. J., Vreeswijk, R., van Gool, W. A. and Eikelenboom, P. (2008). Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients. International Journal of Geriatric Psychiatry, 23, 943–948. doi:10.1002/gps.2015.Google Scholar
Loddick, S. A. and Rothwell, N. J. (1999). Mechanisms of tumor necrosis factor alpha action on neurodegeneration: interaction with insulin-like growth factor-1. Proceedings of the National Academy of Sciences, 96, 9449–9451.Google Scholar
Maes, M., Twisk, F. N. and Ringel, K. (2012). Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychotherapy and Psychosomatics, 81, 286–295. doi:10.1159/000336803.Google Scholar
Magaki, S., Mueller, C., Dickson, C. and Kirsch, W. (2007). Increased production of inflammatory cytokines in mild cognitive impairment. Experimental Gerontology, 42, 233–240.Google Scholar
Magierska, J., Magierski, R., Fendler, W., Kłoszewska, I. and Sobów, T. M. (2012). Clinical application of the Polish adaptation of the Montreal Cognitive Assessment (MoCA) test in screening for cognitive impairment. Neurologia i Neurochirurgia Polska, 46, 130–139.Google Scholar
Masiak, M. and Przychoda-Masiak, J. (2002). International Neuropsychiatric Version. Polish Version 5.0.0. Lublin: Katedra i Klinika Psychiatrii Akademii Medycznej w Lublinie.Google Scholar
Mu, D. L. et al. (2010). High serum cortisol level is associated with increased risk of delirium after coronary artery bypass graft surgery: a prospective cohort study. Critical Care, 14, R238. doi:10.1186/cc9393.CrossRefGoogle ScholarPubMed
Munster, B. C. et al. (2008). Time-course of cytokines during delirium in elderly patients with hip fractures. Journal of the American Geriatric Society, 56, 1704–1709. doi:10.1111/j.1532-5415.2008.01851.x.Google Scholar
Munster, B. C. et al. (2010). Cortisol, interleukins and S100B in delirium in the elderly. Brain and Cognition, 74, 18–23. doi:10.1016/j.bandc.2010.05.010.CrossRefGoogle ScholarPubMed
Nadeau, S. and Rivest, S. (1999). Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors in the rat brain: a view from the blood-brain barrier. Neuroscience, 93, 1449–1464.Google Scholar
Nasreddine, Z. S. et al. (2005). The Montreal Cognitive Assessment (MoCA). A brief screening tool for mild cognitive impairment. Journal of the American Geriatric Society, 53, 695–699.CrossRefGoogle Scholar
Opal, S. M. and DePalo, V. A. (2000). Anti-inflammatory cytokines. Chest, 117, 1162–1172.Google Scholar
Peavy, G. M. et al. (2012). The influence of chronic stress on dementia-related diagnostic change in older adults. Alzheimer Disease and Associated Disorders, 26, 260–266. doi:10.1097/WAD.0b013e3182389a9c.Google Scholar
Plaschke, K. et al. (2010). Early postoperative delirium after open-heart cardiac surgery is associated with decreased bispectral EEG and increased cortisol and interleukin-6. Intensive Care Medicine, 36, 2081–2089. doi:10.1007/s00134-010-2004-4.Google Scholar
Reinsfelt, B., Ricksten, S. E., Zetterberg, H., Blennow, K., Fredén-Lindqvist, J. and Westerlind, A. (2012). Cerebrospinal fluid markers of brain injury, inflammation, and blood-brain barrier dysfunction in cardiac surgery. Annals of Thoracic Surgery, 94, 549–555. doi:10.1016/j.athoracsur.2012.04.044.Google Scholar
Robinson, T. N., Wu, D. S., Pointer, L. F., Dunn, C. L. and Moss, M. (2012). Preoperative cognitive dysfunction is related to adverse postoperative outcomes in the elderly. Journal of the American College of Surgeons, 215, 12–17. doi:10.1016/j.jamcollsurg.2012.02.007.Google Scholar
Roth-Isigkeit, A., Borstel, T. V., Seyfarth, M. and Schmucker, P. (1999). Perioperative serum levels of tumor necrosis-factor alpha (TNF-alpha), IL-1 beta, IL-6, IL-10 and soluble IL-2 receptor in patients undergoing cardiac surgery with cardiopulmonary bypass without and with correction for haemodilution. Clinical & Experimental Immunology, 118, 242–246.Google Scholar
Rudolph, J. L. et al. (2006). Impaired executive function is associated with delirium after coronary artery bypass graft surgery. Journal of the American Geriatric Society, 54, 937–941.Google Scholar
Rudolph, J. L. et al. (2008). Chemokines are associated with delirium after cardiac surgery. The Journals of Geronotology, Series A, Biological Science and Medical Science, 63, 184–189.Google Scholar
Rudolph, J. L. et al. (2009). Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation, 20, 229–236. doi:10.1161/CIRCULATIONAHA.108.795260.Google Scholar
Saczynski, J. S. et al. (2012). Cognitive trajectories after postoperative delirium. New England Journal of Medicine, 5, 30–39. doi:10.1056/NEJMoa1112923.Google Scholar
Sheehan, D. V. et al. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22–33.Google Scholar
Siddiqi, N., House, A. O. and Holmes, J. D. (2006). Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age and Ageing, 35, 350–364.Google Scholar
Simone, M. J. and Tan, Z. S. (2011). The role of inflammation in the patho-genesis of delirium and dementia in older adults: a review. CNS Neuroscience & Therapeutics, 17, 506–513. doi:10.1111/j.1755-5949.2010.00173.x.CrossRefGoogle Scholar
Trysberg, E., Blennow, K., Zachrisson, O. and Tarkowski, A. (2004). Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement. Arthritis Research & Therapy, 6, R551–556.Google Scholar
Velazquez, E. J. et al. (2012). Long-term survival of patients with ischemic cardiomyopathy treated by coronary artery bypass grafting versus medical therapy. Annals of Thoracic Surgery, 93, 523–530. doi:10.1016/j.athoracsur.2011.10.064.Google Scholar
Venters, H. D., Tang, Q., Liu, Q., VanHoy, R. W., Dantzer, R. and Kelley, K. W. (1999). A new mechanism of neurodegeneration: a proinflammatory cytokine inhibits receptor signaling by a survival peptide. Proceedings of the National Academy of Sciences, 969, 879–884.Google Scholar
Vicchio, M., Feo, M. D., Giordano, S., Provenzano, R., Cotrufo, M. and Nappi, G. (2012). Coronary artery bypass grafting associated to aortic valve replacement in the elderly: survival and quality of life. Journal of Cardiothoracic Surgery, 7, 13. doi:10.1186/1749-8090-7-13.CrossRefGoogle ScholarPubMed
War Department Adjutant General's Office (1944). Trailmaking Tests A and B. Washington, DC.Google Scholar
Xing, Z. et al. (1998). IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. Journal of Clinical Investigation, 101, 311–320.Google Scholar
Zhang, Z., Wu, Y., Zhao, Y., Xiao, X., Liu, J. and Zhou, X. (2013). Dynamic changes in HMGB1 levels correlate with inflammatory responses during cardiopulmonary bypass. Experimental and Therapeutic Medicine, 5, 1523–1527. Epub 2013 Mar 22.Google Scholar