Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
We tested the hypothesis that elevated postoperative interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations are associated with short- and medium-term impairment of cognitive functions in patients after coronary artery surgery using cardiopulmonary bypass.
Eighty-six age- and education-balanced patients ≥55 years of age undergoing elective coronary artery bypass surgery with cardiopulmonary bypass and 28 nonsurgical controls with coronary artery disease were enrolled. Recent verbal and nonverbal memory and executive functions were assessed before surgery and at 1 week and 3 months after surgery using a cognitive test battery. IL-6 concentrations were measured before surgery and 4 h after cardiopulmonary bypass, and CRP concentrations were measured before surgery and at 24 and 72 h after anesthetic induction. Overall cognitive function between high and low biomarker concentration groups was analyzed by the Wilcoxon rank-sum test.
Recent memory was at least 1 standard deviation (SD) impaired at 1 week and 3 months in the high-CRP compared with low-CRP and in the high-IL-6 compared with low-IL-6 concentration groups. Overall cognitive function was significantly (P = 0.04 and P = 0.01, respectively) different between the high- and low-CRP concentration groups (CRP assayed 24 h after anesthetic induction) at both 1 week and 3 months. Overall cognitive function was also significantly (P = 0.04) different between the high- and low-IL-6 concentration groups at 1 week after surgery.
The results suggest that elevated postoperative IL-6 and CRP concentrations are associated with the subsequent development of short- and medium-term impairment of cognitive functions after coronary artery surgery.
- Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001;344(6):395–402. CrossRef
- Selnes OA, Goldsborough MA, Borowicz LM, McKhann GM. Neurobehavioural sequelae of cardiopulmonary bypass. Lancet. 1999;353(9164):1601–6. CrossRef
- Bedford PD. Adverse cerebral effects of anaesthesia on old people. Lancet. 1955;269(6884):259–63. CrossRef
- Phillips-Bute B, Mathew JP, Blumenthal JA, Grocott HP, Laskowitz DT, Jones RH, Mark DB, Newman MF. Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery. Psychosom Med. 2006;68(3):369–75. CrossRef
- Rasmussen LS, Christiansen M, Hansen PB, Moller JT. Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anaesthesiol Scand. 1999;43(5):495–500. CrossRef
- Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. 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. CrossRef
- Wilmore DW, Kehlet H. Management of patients in fast track surgery. BMJ. 2001;322(7284):473–6. CrossRef
- Marshall SI, Chung F. Discharge criteria and complications after ambulatory surgery. Anesth Analg. 1999;88(3):508–17. CrossRef
- Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, Aggarwal A, Marschall K, Graham SH, Ley C. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med. 1996;335(25):1857–63. CrossRef
- Ancelin ML, de Roquefeuil G, Ledesert B, Bonnel F, Cheminal JC, Ritchie K. Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. Br J Psychiatry. 2001;178:360–6. CrossRef
- Hudetz JA, Iqbal Z, Gandhi SD, Patterson KM, Hyde TF, Reddy DM, Hudetz AG, Warltier DC. Postoperative cognitive dysfunction in older patients with a history of alcohol abuse. Anesthesiology. 2007;106(3):423–30. CrossRef
- Cremer J, Martin M, Redl H, Bahrami S, Abraham C, Graeter T, Haverich A, Schlag G, Borst HG. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg. 1996;61(6):1714–20. CrossRef
- Deng MC, Dasch B, Erren M, Mollhoff T, Scheld HH. Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg. 1996;62(1):184–90. CrossRef
- Hennein HA, Ebba H, Rodriguez JL, Merrick SH, Keith FM, Bronstein MH, Leung JM, Mangano DT, Greenfield LJ, Rankin JS. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg. 1994;108(4):626–35.
- Kalman J, Juhasz A, Bogats G, Babik B, Rimanoczy A, Janka Z, Penke B, Palotas A. Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochem Int. 2006;48(3):177–80. CrossRef
- Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C, Moric M, Caicedo MS, Tuman KJ. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology. 2006;104(3):403–10. CrossRef
- Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007;21(2):153–60. CrossRef
- Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH Jr, Heimovitz H, Cohen HJ, Wallace R. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12. CrossRef
- Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, Seeman TE. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002;59(3):371–8.
- Yaffe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, Kritchevsky S, Launer L, Kuller L, Rubin S, Harris T. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003;61(1):76–80.
- Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002;52(2):168–74. CrossRef
- Rasmussen LS, Larsen K, Houx P, Skovgaard LT, Hanning CD, Moller JT. The assessment of postoperative cognitive function. Acta Anaesthesiol Scand. 2001;45(3):275–89. CrossRef
- Hachinski V, Munoz D. Vascular factors in cognitive impairment: where are we now? Ann N Y Acad Sci. 2000;903:1–5. CrossRef
- Benedict HB, Schretlen D, Groninger L, Brandt J. Hopkins verbal learning test—revised: normative data and analysis of inter-form and test–retest reliability. Clin Neuropsychol. 1998;12(1):43–55.
- Wilson B, Cockburn J, Baddeley A, Hiorns R. The development and validation of a test battery for detecting and monitoring everyday memory problems. J Clin Exp Neuropsychol. 1989;11(6):855–70. CrossRef
- Delis DC, Kaplan E, Kramer JH. Delis–Kaplan Executive Function System (D-KEFS). San Antonio: The Psychological Corporation; 2001.
- Benedict RH, Schretlen D, Groninger L, Dobraski M, Shpritz B. Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and validity. Psychol Assess. 1996;8(2):145–53. CrossRef
- Wechsler DA. Wechsler adult intelligence scale, 3rd edn. San Antonio: The Psychological Corporation; 1997.
- Randolph C. Repeatable battery for the assessment of neurological status. San Antonio, TX: Psychological Corporation; 1998.
- Benton AL, Hamsher K. Multilingual aphasia examination. Iowa City, IA: AJA Associates; 1989.
- Bohnen N, Twijnstra A, Jolles J. Performance in the Stroop color word test in relationship to the persistence of symptoms following mild head injury. Acta Neurol Scand. 1992;85(2):116–21. CrossRef
- Franke A, Lante W, Fackeldey V, Becker HP, Kurig E, Zoller LG, Weinhold C, Markewitz A. Pro-inflammatory cytokines after different kinds of cardio-thoracic surgical procedures: is what we see what we know? Eur J Cardiothorac Surg. 2005;28(4):569–75. CrossRef
- Bartoc C, Frumento RJ, Jalbout M, Bennett-Guerrero E, Du E, Nishanian E. A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2006;20(2):217–22. CrossRef
- Roytblat L, Talmor D, Rachinsky M, Greemberg L, Pekar A, Appelbaum A, Gurman GM, Shapira Y, Duvdenani A. Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg. 1998;87(2):266–71. CrossRef
- Hudetz JA, Iqbal Z, Gandhi SD, Patterson KM, Byrne AJ, Hudetz AG, Pagel PS, Warltier DC. Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery. Acta Anaesthesiol Scand. 2009;53(7):864–72. CrossRef
- Newman SP. Analysis and interpretation of neuropsychologic tests in cardiac surgery. Ann Thorac Surg. 1995;59(5):1351–5. CrossRef
- Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97(1):215–52. CrossRef
- Xu J, Wen Y, Cibelli M, Ma D, Maze M. Postoperative cognitive dysfunction: a role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2006;105:A1175.
- van der Mast RC. Postoperative delirium. Dement Geriatr Cogn Disord. 1999;10(5):401–5. CrossRef
- Shalaby MR, Waage A, Aarden L, Espevik T. Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo. Clin Immunol Immunopathol. 1989;53(3):488–98. CrossRef
- Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993;119(8):771–8.
- Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond). 1990;79(2):161–5.
- Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses. 2004;62(4):499–506. CrossRef
- Dijkstra JB, Houx PJ, Jolles J. Cognition after major surgery in the elderly: test performance and complaints. Br J Anaesth. 1999;82(6):867–74.
- Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibanaz MT, Moller JT. Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002;96(6):1351–7. CrossRef
- Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008;108(1):18–30. CrossRef
- Gunning-Dixon FM, Raz N. Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study. Neuropsychologia. 2003;41(14):1929–41. CrossRef
- Ihara H, Berrios GE, London M. Group and case study of the dysexecutive syndrome in alcoholism without amnesia. J Neurol Neurosurg Psychiatry. 2000;68(6):731–7. CrossRef
- Teunissen CE, van Boxtel MP, Bosma H, Bosmans E, Delanghe J, De Bruijn C, Wauters A, Maes M, Jolles J, Steinbusch HW, de Vente J. Inflammation markers in relation to cognition in a healthy aging population. J Neuroimmunol. 2003;134(1-2):142–50. CrossRef
- Vernaglione L, Cristofano C, Muscogiuri P, Chimienti S. Does atorvastatin influence serum C-reactive protein levels in patients on long-term hemodialysis? Am J Kidney Dis. 2004;43(3):471–8. CrossRef
- American Heart Association. Heart Disease and Stroke Statistics: 2004 Update. Dallas: American Heart Association; 2003.
- Elevated postoperative inflammatory biomarkers are associated with short- and medium-term cognitive dysfunction after coronary artery surgery
Journal of Anesthesia
Volume 25, Issue 1 , pp 1-9
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- C-reactive protein
- Coronary artery bypass graft
- Cardiopulmonary bypass
- Postoperative cognitive dysfunction
- Industry Sectors
- Author Affiliations
- 1. Department of Anesthesiology, Clement J. Zablocki Veterans Administration Medical Center, 5000 W. National Avenue, Milwaukee, WI, 53295, USA
- 2. Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA