Postoperative Cognitive Dysfunction after Coronary Artery Bypass Grafting

Shi-Min Yuan Hong Lin About the authors

Abstract

Postoperative cognitive dysfunction is a common complication following cardiac surgery. The incidence of cognitive dysfunction is more pronounced in patients receiving a cardiac operation than in those undergoing a non-cardiac operation. Clinical observations demonstrated that pulsatile flow was superior to nonpulsatile flow, and membrane oxygenator was superior to bubble oxygenator in terms of postoperative cognitive status. Nevertheless, cognitive assessments in patients receiving an on-pump and off-pump coronary artery bypass surgery have yielded inconsistent results. The exact mechanisms of postoperative cognitive dysfunction following coronary artery bypass grafting remain uncertain. The dual effects, neuroprotective and neurotoxic, of anesthetics should be thoroughly investigated. The diagnosis should be based on a comprehensive cognitive evaluation with neuropsychiatric tests, cerebral biomarker inspections, and electroencephalographic examination. The management strategies for cognitive dysfunction can be preventive or therapeutic. The preventive strategies of modifying surgical facilities and techniques can be effective for preventing the development of postoperative cognitive dysfunction. Investigational therapies may offer novel strategies of treatments. Anesthetic preconditioning might be helpful for the improvement of this dysfunction.

Keywords:
Cognitive Dysfunction; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Postoperative Complications

INTRODUCTION

Postoperative cognitive dysfunction (POCD), characterized by impairment of attention, concentration, and memory with possible long-term implications, is a frequent neurological sequela following cardiac surgery. According to duration, POCD can be classified into two types: short-term and long-term. The former is usually a transitory cognitive decline lasting up to 6 weeks after a cardiac operation with an incidence of 20-50%, whereas the latter can be a subtle deterioration of cognitive function occurring six months after an operation with an incidence of 10-30%[11 Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, et al; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001;344(6):395-402.]. However, POCD might occur several years after an operation. The incidence of POCD depends on the types of operation, and it is more pronounced in patients receiving a cardiac operation than in those undergoing a non-cardiac operation[22 Jungwirth B, Zieglgänsberger W, Kochs E, Rammes G. Anesthesia and postoperative cognitive dysfunction (POCD). Mini Rev Med Chem. 2009;9(14):1568-79.]. A retrospective study demonstrated that coronary artery bypass grafting (CABG) is the most common cause of POCD after a cardiac operation with an incidence of 37.6% in 7 days and 20.8% in the 3rd month of the postoperative period[33 Ge Y, Ma Z, Shi H, Zhao Y, Gu X, Wei H. Incidence and risk factors of postoperative cognitive dysfunction in patients underwent coronary artery bypass grafting surgery. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2014;39(10):1049-55.].

POCD should be distinguished with relevant concepts, such as postoperative delirium and vascular dementia. Postoperative delirium is an acute mental syndrome characterized by a transient fluctuating disturbance of consciousness, attention, cognition, and perception as a common complication of surgery, occurring in 36.86% of the surgical patients[44 Bryson GL, Wyand A, Wozny D, Rees L, Taljaard M, Nathan H. A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair. Can J Anaesth. 2011;58(3):246-55.]. The significant risk factors responsible for postoperative delirium were peripheral arterial disease, preexisting cerebrovascular disorders, and a reduced preoperative Hasegawa-dementia score[55 Otomo S, Maekawa K, Goto T, Baba T, Yoshitake A. Pre-existing cerebral infarcts as a risk factor for delirium after coronary artery bypass graft surgery. Interact Cardiovasc Thorac Surg. 2013;17(5):799-804.]. POCD is a subtler deficit affecting patients' cognition, including verbal, visual, language, visuospatial, attention, and concentration aspects[44 Bryson GL, Wyand A, Wozny D, Rees L, Taljaard M, Nathan H. A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair. Can J Anaesth. 2011;58(3):246-55.]. A more delayed development of POCD may indicate a poorer prognosis. Associated POCD and delirium was noted in 77% of aortic surgical patients at discharge, which suggests that both conditions could share a common mechanism[44 Bryson GL, Wyand A, Wozny D, Rees L, Taljaard M, Nathan H. A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair. Can J Anaesth. 2011;58(3):246-55.]. Vascular dementia, as a result of any vasculopathies, is the most common type of dementia in elderly patients, who often have significant impairment of social or occupational functions, usually accompanied by focal motor and sensory abnormalities[66 McVeigh C, Passmore P. Vascular dementia: prevention and treatment. Clin Interv Aging. 2006;1(3):229-35.].

Cognitive assessments between conventional CABG with the use of cardiopulmonary bypass (CPB) (on-pump) and CABG without CPB (off-pump) yielded inconsistent results. The exact mechanisms of development of POCD following CABG and cognitive impact of anesthetics remain uncertain. The diagnosis and treatment of POCD are still challenging. This article aims to present an overview of POCD following CABG.

Predictive Risk Factors

Predictive risk factors of POCD may include old age, preexisting cerebral, cardiac, and vascular diseases, alcohol abuse, low educational level, and intra- and postoperative complications[77 Rundshagen I. Postoperative cognitive dysfunction. Dtsch Arztebl Int. 2014;111(8):119-25.]. A univariant analysis revealed that older age, female gender, higher bleeding episodes, and increased postoperative creatinine levels were more significantly associated with POCD[88 Habib S, Khan Au, Afridi MI, Saeed A, Jan AF, Amjad N. Frequency and predictors of cognitive decline in patients undergoing coronary artery bypass graft surgery. J Coll Physicians Surg Pak. 2014;24(8):543-8.]. Laalou et al.[99 Laalou FZ, Carre AC, Forestier C, Sellal F, Langeron O, Pain L. Pathophysiology of post-operative cognitive dysfunction: current hypotheses. J Chir (Paris). 2008;145(4):323-30.] described that POCD was age- and observational time-related, with an incidence of 23-29% in patients aged 60-69 and >70 years in one week, and 14% in those aged >70 years in the 3rd month of the postoperative period. Cerebral hypoperfusion is an important risk factor contributing to postoperative brain damage, especially in atherosclerotic patients due to hypoperfusion-induced impaired clearance of microemboli and worsened ischemic damage[1010 Polunina AG, Golukhova EZ, Guekht AB, Lefterova NP, Bokeria LA. Cognitive dysfunction after on-pump operations: neuropsychological characteristics and optimal core battery of tests. Stroke Res Treat. 2014;2014:302824.]. POCD can result from systemic or cerebral inflammation due to neuronal injuries[1111 van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012;67(3):280-93.]. Surgical operation might trigger brain mast cell degranulation, microglia activation, and release of inflammatory cytokines, thus, leading to neuronal damages, and activated brain mast cells might induce neuronal apoptosis[1212 Zhang X, Dong H, Li N, Zhang S, Sun J, Zhang S, et al. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis. J Neuroinflammation. 2016;13(1):127.]. The association between increased levels of plasma inflammatory mediators (interleukin-1, interleukin-6, tumor necrosis factor-α, and C-reactive protein) and cognitive dysfunction has been found in postoperative patients and could eventually predict future cognitive decline[1313 Kudoh A, Takase H, Katagai H, Takazawa T. Postoperative interleukin-6 and cortisol concentrations in elderly patients with postoperative confusion. Neuroimmunomodulation. 2005;12(1):60-6.]. Autonomic nervous suppression in relation to neuroendocrine response as well as cytokine production to surgery and anesthesia might play an important role in the development of POCD[99 Laalou FZ, Carre AC, Forestier C, Sellal F, Langeron O, Pain L. Pathophysiology of post-operative cognitive dysfunction: current hypotheses. J Chir (Paris). 2008;145(4):323-30.]. Other conditions like increased plasma cortisol levels via stimulation of the hypothalamic-pituitary axis[99 Laalou FZ, Carre AC, Forestier C, Sellal F, Langeron O, Pain L. Pathophysiology of post-operative cognitive dysfunction: current hypotheses. J Chir (Paris). 2008;145(4):323-30.] and preexisting cerebrovascular disease[1414 Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.] could be specific risk factors of POCD.

Diagnosis

Neuropsychiatric Tests

POCD is verified by employing batteries of psychometric tests performed pre- and postoperatively to assess cognitive performance. Currently, there is no gold standard, but some tests (Rey auditory verbal learning test, Trail-making A, Trail-making B, and Grooved pegboard) were recommended as core tests as proposed by Murkin et al.[1515 Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg. 1995;59(5):1289-95.] in 1995. Typically, a battery of tests is composed of a comprehensive assessment of the cognitive status, including memory, attention, language, executive function, and motor speed[1414 Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.]. The Mini-Mental Status Examination (MMSE), a commonly used screening test for dementia with remarkable validity and reliability[1616 Saraçli Ö, Akca AS, Atasoy N, Önder Ö, Senormanci Ö, Kaygisiz I, et al. The relationship between quality of life and cognitive functions, anxiety and depression among hospitalized elderly patients. Clin Psychopharmacol Neurosci. 2015;13(2):194-200.], is sometimes used to quantify POCD[1717 Helkala EL, Kivipelto M, Hallikainen M, Alhainen K, Heinonen H, Tuomilehto J, et al. Usefulness of repeated presentation of Mini-Mental State Examination as a diagnostic procedure: a population-based study. Acta Neurol Scand. 2002;106(6):341-6.], and an MMSE value below 25 is regarded as POCD[1818 Jildenstål PK, Hallén JL, Rawal N, Berggren L. Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery? J Anesth Clin Res. 2012;3(6):220.]. However, comparing cognitive function before operation and adjustment of age or education level is important before determining the POCD. In addition, the Confusion Assessment Method (CAM) and the Cognitive Failures Questionnaire (CFQ) were used pre- and postoperatively to evaluate the cognitive status[1818 Jildenstål PK, Hallén JL, Rawal N, Berggren L. Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery? J Anesth Clin Res. 2012;3(6):220.]. The neuropsychiatric tests that are used in clinical practice are shown in Table 1[88 Habib S, Khan Au, Afridi MI, Saeed A, Jan AF, Amjad N. Frequency and predictors of cognitive decline in patients undergoing coronary artery bypass graft surgery. J Coll Physicians Surg Pak. 2014;24(8):543-8.,1515 Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg. 1995;59(5):1289-95.,1616 Saraçli Ö, Akca AS, Atasoy N, Önder Ö, Senormanci Ö, Kaygisiz I, et al. The relationship between quality of life and cognitive functions, anxiety and depression among hospitalized elderly patients. Clin Psychopharmacol Neurosci. 2015;13(2):194-200.,1818 Jildenstål PK, Hallén JL, Rawal N, Berggren L. Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery? J Anesth Clin Res. 2012;3(6):220.

19 Stroobant N, Van Nooten G, Belleghem Y, Vingerhoets G. Short-term and long-term neurocognitive outcome in on-pump versus off-pump CABG. Eur J Cardiothorac Surg. 2002;22(4):559-64.

20 Benabarre A, Vieta E, Martínez-Arán A, Garcia-Garcia M, Martín F, Lomeña F, et al. Neuropsychological disturbances and cerebral blood flow in bipolar disorder. Aust N Z J Psychiatry. 2005;39(4):227-34.
-2121 Proust-Lima C, Amieva H, Dartigues JF, Jacqmin-Gadda H. Sensitivity of four psychometric tests to measure cognitive changes in brain aging-population-based studies. Am J Epidemiol. 2007;165(3):344-50.]. Habib et al.[88 Habib S, Khan Au, Afridi MI, Saeed A, Jan AF, Amjad N. Frequency and predictors of cognitive decline in patients undergoing coronary artery bypass graft surgery. J Coll Physicians Surg Pak. 2014;24(8):543-8.] noted that the McNair scale was more evident than MMSE. Proust-Lima et al.[2121 Proust-Lima C, Amieva H, Dartigues JF, Jacqmin-Gadda H. Sensitivity of four psychometric tests to measure cognitive changes in brain aging-population-based studies. Am J Epidemiol. 2007;165(3):344-50.] found that MMSE and Benton Visual Retention Test showed a superior sensitivity over Isaacs Set Test and Digit Symbol Substitution Test.

Table 1
Neuropsychiatric tests for cognitive assessment in clinical practice.

Cerebral Biomarker Inspections

Biomarkers in relation to POCD have been described as β-amyloid peptide (βAP), tau, phospho-tau, apoE, interleukin-6, C-reactive protein, cortisol, S100β, and neuron-specific enolase (NSE). Increased serum tau level was seen in patients with cognitive decline after CPB, and increased cerebrospinal fluid βAP and tau levels were similar to those having Alzheimer's disease. Serum interleukin-6, C-reactive protein, and NSE are important indicators of POCD following CABG[2222 Reis HJ, Oliveira AC, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Yalvaç ME, et al. Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient. Cur Mol Med. 2014;14(9):1155-63.]. NSE, S100, and S100β are more sensitive for detecting cerebral structural and functional damages in patients undergoing various cardiac operations, and all peaked at the end of CPB[2323 Yuan SM. Biomarkers of cerebral injury in cardiac surgery. Anadolu Kardiyol Derg. 2014;14(7):638-45.]. Alternative potential indicators for POCD include neuro-filament heavy chain (NfH), iso-prostane (isoP), and reduced cerebral perfusion/hypoxia[2222 Reis HJ, Oliveira AC, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Yalvaç ME, et al. Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient. Cur Mol Med. 2014;14(9):1155-63.].

Electroencephalography

Increased lower frequencies, reduced complex activities, and incoherent cortical regions/fast rhythms shown on the electroencephalogram may indicate POCD[2222 Reis HJ, Oliveira AC, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Yalvaç ME, et al. Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient. Cur Mol Med. 2014;14(9):1155-63.].

Literature Review

Pertinent literature was retrieved for articles published between 2000-2018. The search terms included "coronary artery bypass grafting", "on-pump", "off-pump", "cognitive decline", "postoperative cognitive dysfunction", "diagnosis", and "treatment". A total of 28 prospective or retrospective research articles were obtained which involved 3.373 patients[2424 Kumpaitiene B, Svagzdiene M, Drigotiene I, Sirvinskas E, Sepetiene R, Zakelis R, et al. Correlation among decreased regional cerebral oxygen saturation, blood levels of brain injury biomarkers, and cognitive disorder. J Int Med Res. 22018;46(9):3621-9.

25 Thomaidou E, Argiriadou H, Vretzakis G, Megari K, Taskos N, Chatzigeorgiou G, et al. Perioperative use of erythromycin reduces cognitive decline after coronary artery bypass grafting surgery: a pilot study. Clin Neuropharmacol. 2017;40(5):195-200.

26 Kok WF, Koerts J, Tucha O, Scheeren TW, Absalom AR. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery. Anaesthesia. 2017;72(3):359-69.

27 Silva FP, Schmidt AP, Valentin LS, Pinto KO, Zeferino SP, Oses JP, et al. S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery: a prospective observational study. Eur J Anaesthesiol. 2016;33(9):681-9.

28 Öztürk S, Saçar M, Baltalarli A, Öztürk I. Effect of the type of cardiopulmonary bypass pump flow on postoperative cognitive function in patients undergoing isolated coronary artery surgery. Anatol J Cardiol. 2016;16(11):875-80.

29 Oldham MA, Hawkins KA, Yuh DD, Dewar ML, Darr UM, Lysyy T, et al. Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study. Int Psychogeriatr. 2015;27(12):1929-38.

30 Hassani S, Alipour A, Darvishi Khezri H, Firouzian A, Emami Zeydi A, Gholipour Baradari A, et al. Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2015;232(5):843-50.

31 Dong S, Li CL, Liang WD, Chen MH, Bi YT, Li XW. Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery. Peptides. 2014;59:70-4.

32 Trubnikova OA, Mamontova AS, Syrova ID, Maleva OV, Barbarash OL. Does preoperative mild cognitive impairment predict postoperative cognitive dysfunction after on-pump coronary bypass surgery? J Alzheimers Dis. 2014;42(Suppl 3):S45-51.

33 Kok WF, van Harten AE, Koene BM, Mariani MA, Koerts J, Tucha O, et al. A pilot study of cerebral tissue oxygenation and postoperative cognitive dysfunction among patients undergoing coronary artery bypass grafting randomised to surgery with or without cardiopulmonary bypass. Anaesthesia. 2014;69(6):613-22.

34 Szwed K, Pawliszak W, Anisimowicz L, Bucinski A, Borkowska A. Short-term outcome of attention and executive functions from aorta no-touch and traditional off-pump coronary artery bypass surgery. World J Biol Psychiatry. 2014;15(5):397-403.

35 Fontes MT, McDonagh DL, Phillips-Bute B, Welsby IJ, Podgoreanu MV, Fontes ML, et al; Neurologic Outcome Research Group (NORG) of the Duke Heart Center. Arterial hyperoxia during cardiopulmonary bypass and postoperative cognitive dysfunction. J Cardiothorac Vasc Anesth. 2014;28(3):462-6.

36 Sirvinskas E, Usas E, Mankute A, Raliene L, Jakuska P, Lenkutis T, et al. Effects of intraoperative external head cooling on short-term cognitive function in patients after coronary artery bypass graft surgery. Perfusion. 2014;29(2):124-9.

37 Joung KW, Rhim JH, Chin JH, Kim WJ, Choi DK, Lee EH, et al. Effect of remote ischemic preconditioning on cognitive function after off-pump coronary artery bypass graft: a pilot study. Korean J Anesthesiol. 2013;65(5):418-24.

38 Mu DL, Li LH, Wang DX, Li N, Shan GJ, Li J, et al. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: a prospective cohort study. PLoS One. 2013;8(10):e77637.

39 Kadoi Y, Kawauchi C, Kuroda M, Takahashi K, Saito S, Fujita N, et al. Association between cerebrovascular carbon dioxide reactivity and postoperative short-term and long-term cognitive dysfunction in patients with diabetes mellitus. J Anesth. 2011;25(5):641-7.

40 de Tournay-Jetté E, Dupuis G, Bherer L, Deschamps A, Cartier R, Denault A. The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011;25(1):95-104.

41 Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009;87(1):36-44.

42 Haljan G, Maitland A, Buchan A, Arora RC, King M, Haigh J, et al. The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial. Stroke. 2009;40(8):2769-75.

43 Silbert BS, Evered LA, Scott DA, Cowie TF. The apolipoprotein E epsilon4 allele is not associated with cognitive dysfunction in cardiac surgery. Ann Thorac Surg. 2008;86(3):841-7.

44 Jensen BØ, Rasmussen LS, Steinbrüchel DA. Cognitive outcomes in elderly high-risk patients 1 year after off-pump versus on-pump coronary artery bypass grafting. A randomized trial. Eur J Cardiothorac Surg. 2008;34(5):1016-21.

45 Hogue CW, Fucetola R, Hershey T, Freedland K, Dávila-Román VG, Goate AM, et al. Risk factors for neurocognitive dysfunction after cardiac surgery in postmenopausal women. Ann Thorac Surg. 2008;86(2):511-6.

46 Puskas F, Grocott HP, White WD, Mathew JP, Newman MF, Bar-Yosef S. Intraoperative hyperglycemia and cognitive decline after CABG. Ann Thorac Surg. 2007;84(5):1467-73.

47 Kadoi Y, Goto F. Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery. J Anesth. 2007;21(3):330-5.

48 Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery. Surg Today. 2006;36(12):1053-7.

49 Jensen BO, Hughes P, Rasmussen LS, Pedersen PU, Steinbrüchel DA. Cognitive outcomes in elderly high-risk patients after off-pump versus conventional coronary artery bypass grafting: a randomized trial. Circulation. 2006;113(24):2790-5.

50 Silbert BS, Scott DA, Evered LA, Lewis MS, Kalpokas M, Maruff P, et al. A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly. Anesthesiology. 2006;104(6):1137-45.
-5151 Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg. 2002;95(5):1134-41.]. The early and late rates of POCD were 34% and 27.6%, respectively. The statistical analysis made by Fisher's exact test for comparisons of frequencies showed that the early POCD rate was lower, but the late POCD rate was higher in CABG in comparison to OPCAB patients (Figure 1). The disparities in the early and late POCD incidences compared to the results reported in the literature were probably due to the differences in literature selection. Additionally, the literature review outstood some attenuators and intensifiers of POCD following CABG procedures (Table 2).

Fig. 1
The outcomes of the review with a depiction of early and late postoperative cognitive dysfunctions following coronary artery bypass grafting.

*Comparisons of frequencies were made by Fisher's exact test.

CABG=coronary artery bypass grafting; m=months; OPCAB=off-pump coronary artery bypass; POCD=postoperative cognitive dysfunction

Table 2
Literature review of representative publications on postoperative cognitive dysfunction following coronary artery bypass grafting.

Aykut et al.[5252 Aykut K, Albayrak G, Guzeloglu M, Hazan E, Tufekci M, Erdogan I. Pulsatile versus non-pulsatile flow to reduce cognitive decline after coronary artery bypass surgery: a randomized prospective clinical trial. J Cardiovasc Dis Res. 2013;4(2):127-9.] prospectively compared the effect of pulsatile and nonpulsatile flow on cognitive functions of patients undergoing CABG. The cognitive performance was evaluated with the Montreal Cognitive Assessment (MoCA) test one day before and one month after the operation. They observed an overall POCD rate of 17.3% in pulsatile and 35.6% in nonpulsatile flow group. Besides, mild cognitive impairment was seen more in the nonpulsatile than in the pulsatile flow group. This result was interpreted as pulsatile flow ensuring a lower systemic vascular resistance and higher oxygen consumption. The pulsatile flow might increase cerebral blood flow, aerobic metabolism, and oxygen delivery, and reduce cerebral vascular resistance[5353 Undar A, Eichstaedt HC, Bigley JE, Deady BA, Porter AE, Vaughn WK, et al. Effects of pulsatile and nonpulsatile perfusion on cerebral hemodynamics investigated with a new pediatric pump. J Thorac Cardiovasc Surg. 2002;124(2):413-6.]. On the contrary, the nonpulsatile flow does not possess these advantages[5454 Hickey PR, Buckley MJ, Philbin DM. Pulsatile and nonpulsatile cardiopulmonary bypass: review of a counterproductive controversy. Ann Thorac Surg. 1983;36(6):720-37.]. Pulsatile perfusion preserves microcirculatory perfusion over the conventional nonpulsatile perfusion during CPB. The latter is associated with altered microvascular blood flow, increased leukocyte activation, endothelial dysfunction, and increased microvascular resistance along with elevated lactate as an indicator of tissue hypoxia[5555 Koning NJ, Vonk AB, van Barneveld LJ, Beishuizen A, Atasever B, van den Brom CE, et al. Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics. J Appl Physiol (1985). 2012;112(10):1727-34.,5656 O'Neil MP, Fleming JC, Badhwar A, Guo LR. Pulsatile versus nonpulsatile flow during cardiopulmonary bypass: microcirculatory and systemic effects. Ann Thorac Surg. 2012;94(6):2046-53.].

Some authors reported significant cognitive improvement in the first year follow-up period[5757 Lee JD, Lee SJ, Tsushima WT, Yamauchi H, Lau WT, Popper J, et al. Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial. Ann Thorac Surg. 2003;76(1):18-25.], less cognitive impairment in one week[5858 Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg. 2000;69(4):1162-6.], less deteriorated cognitive scores in one and 10 weeks[5959 Zamvar V, Williams D, Hall J, Payne N, Cann C, Young K, et al. Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial. BMJ. 2002;325(7375):1268.], and better neuropsychological performance six months after surgery[1919 Stroobant N, Van Nooten G, Belleghem Y, Vingerhoets G. Short-term and long-term neurocognitive outcome in on-pump versus off-pump CABG. Eur J Cardiothorac Surg. 2002;22(4):559-64.] in OPCAB patients. Emmert et al.[6060 Emmert MY, Seifert B, Wilhelm M, Grünenfelder J, Falk V, Salzberg SP. Aortic no-touch technique makes the difference in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2011;142(6):1499-506.] reported that on-pump CABG showed an increased risk of postoperative stroke. In contrast, the incidence of stroke was low in patients receiving a standardized OPCAB with no-touch techniques for a proximal anastomosis. They hypothesized that the underlying mechanisms of POCD were probably in virtue of cerebral mircroembolic, inflammatory, and non-physiological perfusion of CPB. However, reports revealed no difference in early postoperative cognitive impairment and late cognitive recovery between on-pump CABG and OPCAB procedures[6161 Taggart DP, Browne SM, Halligan PW, Wade DT. Is cardiopulmonary bypass still the cause of cognitive dysfunction after cardiac operations? J Thorac Cardiovasc Surg. 1999;118(3):414-20.

62 Vedin J, Nyman H, Ericsson A, Hylander S, Vaage J. Cognitive function after on or off pump coronary artery bypass grafting. Eur J Cardiothorac Surg. 2006;30(2):305-10.
-6363 Van Dijk D, Jansen EW, Hijman R, Nierich AP, Diephuis JC, Moons KG, et al; Octopus Study Group. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA. 2002;287(11):1405-12.]. Such inconsistent results were explained by different patient selection criteria and low cardiac output during distal anastomoses in OPCAB[6262 Vedin J, Nyman H, Ericsson A, Hylander S, Vaage J. Cognitive function after on or off pump coronary artery bypass grafting. Eur J Cardiothorac Surg. 2006;30(2):305-10.]. Thus, van Dijk et al.[6464 van Dijk D, Moons KG, Keizer AM, Jansen EW, Hijman R, Diephuis JC, et al; Octopus Study Group. Association between early and three month cognitive outcome after off-pump and on-pump coronary bypass surgery. Heart. 2004;90(4):431-4.] concluded that POCD was insignificantly influenced by CPB. In line with this statement, Selnes et al.[1414 Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.] claimed that the late POCD was more likely resulted from preexisting cerebrovascular disorders other than from CPB. The possible explanation for this pervasive inconsistency was that different measures were taken concerning the use of unspecified diagnostic criteria for the assessment of POCD[6565 Beratis IN, Papageorgiou SG. Heart surgery and the risk of cognitive decline. Arch Hellenic Med. 2014;31(2):186-90.], incongruousness of definition of cognitive decline, disparity of statistical methods, and lack of randomized control studies[1414 Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.].

Management

Preventive Measures

Preoperative cognitive screening is a cost-effective way of preventing POCD[1414 Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.]. Intraoperative monitoring of regional cerebral oxygen saturation against prolonged brain desaturation could be associated with an induced incidence of POCD[6666 Colak Z, Borojevic M, Bogovic A, Ivancan V, Biocina B, Majeric-Kogler V. Influence of intraoperative cerebral oximetry monitoring on neurocognitive function after coronary artery bypass surgery: a randomized, prospective study. Eur J Cardiothorac Surg. 2015;47(3):447-54.]. The measures for preventing POCD by modifying surgical facilities, such as reducing particulate and gaseous microemboli (by using cardiotomy, cell-saver, arterial line filtration, anastomotic devices and cannulae with modified blood entry and less shear stress, and membrane oxygenator other than bubble oxygenator), hemostasis (by glucose management, temperature regulation and pH management) and surgical techniques, including OPCAB technique, minimized aortic manipulation with single other than multiple aortic clamping[6767 Hammon JW, Stump DA, Butterworth JF, Moody DM, Rorie K, Deal DD, et al. Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: the effect of reduced aortic manipulation. J Thorac Cardiovasc Surg. 2006;131(1):114-21.,6868 Ates M, Yangel M, Gullu AU, Sensoz Y, Kizilay M, Akcar M. Is single or double aortic clamping safer in terms of cerebral outcome during coronary bypass surgery? Int Heart J. 2006;47(2):185-92.], no-touch technique[3434 Szwed K, Pawliszak W, Anisimowicz L, Bucinski A, Borkowska A. Short-term outcome of attention and executive functions from aorta no-touch and traditional off-pump coronary artery bypass surgery. World J Biol Psychiatry. 2014;15(5):397-403.], and pulsatile rather than non-pulsatile CPB[6969 Whitaker DC, Stygall J, Newman SP. Neuroprotection during cardiac surgery: strategies to reduce cognitive decline. Perfusion. 2002;17(Suppl):69-75.].

Therapeutic Strategies

Potential pharmacologic strategies include investigational (such as piracetam, cholinesterase inhibitors, glutamate N-methyl-D-aspartate antagonists, glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulators, γ-aminobutyric acid-B antagonists, nicotinic receptor agonists, dopamine/norepinephrine re-uptake inhibitors, Ginkgo biloba, coenzyme Q, antioxidants, and growth factors) and therapeutic agents with neuroprotective effects for immediate treatment of POCD (such as sedatives, acetylcholine sterase inhibitor, stimulants, statins, calcium channel antagonist and N-methyl-D-aspartate antagonist)[6969 Whitaker DC, Stygall J, Newman SP. Neuroprotection during cardiac surgery: strategies to reduce cognitive decline. Perfusion. 2002;17(Suppl):69-75.]. However, these agents warrant further evaluations with regard to their long-term efficacies[7070 Raja PV, Blumenthal JA, Doraiswamy PM. Cognitive deficits following coronary artery bypass grafting: prevalence, prognosis, and therapeutic strategies. CNS Spectr. 2004;9(10):763-72.]. Moreover, investigations have proved that anesthetic preconditioning managements may improve POCD incidence. Royse et al.[7171 Royse CF, Andrews DT, Newman SN, Stygall J, Williams Z, Pang J, et al. The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery. Anaesthesia. 2011;66(6):455-64.] investigated the influence of propofol or desflurane on POCD incidence and found that desflurane was associated with a reduced incidence of early POCD in comparison to propofol (49.4% vs. 67.5%, P=0.018). This was interpreted as those anesthetics being potentially neurotoxic but sometimes neuroprotective for ischemia-reperfusion injury[7272 Piriou V, Chiari P, Gateau-Roesch O, Argaud L, Muntean D, Salles D, et al. Desflurane-induced preconditioning alters calcium-induced mitochondrial permeability transition. Anesthesiology. 2004;100(3):581-8.].

The evaluation of anesthetics on cognitive outcome seems to be difficult. This is because anesthetics showed dual neurological impacts: neuroprotective and neurotoxic[7373 Wei H, Inan S. Dual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis. Prog Neuropsychopharmacol Biol Psychiatry. 2013;47:156-61.]. Mechanistic studies have been concentrated on ion channels of the nerve cells, particularly on receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, N-methyl-D-aspartic acid, γ-aminobutyric acid type A, glycine, 5-hydroxytryptamine type 3, and nicotinic acetylcholine receptors[7474 Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, et al. Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg. 2003;97(3):718-40.]. The neuroprotective effects of anesthetics may rely on the reduction of neuronal excitation and enhancement of γ-aminobutyric acid type A receptor function[7575 Zhou C, Liu J, Chen XD. General anesthesia mediated by effects on ion channels. World J Crit Care Med. 2012;1(3):80-93.]. Anesthetic-induced cognitive impairment probably depends on the type and dose of anesthetics, the mode and route of drug delivery, and observational time[22 Jungwirth B, Zieglgänsberger W, Kochs E, Rammes G. Anesthesia and postoperative cognitive dysfunction (POCD). Mini Rev Med Chem. 2009;9(14):1568-79.].

CONCLUSION

The underlying etiologies of POCD following CABG can be complex. A comprehensive postoperative cognitive evaluation with neuropsychiatric tests, cerebral biomarker inspections, and electroencephalographic examination should be performed to assess patients' cognitive status. Inconsistent results of POCD between OPCAB and on-pump CABG warrant further evaluations in well-designed prospective studies. The preventive strategies of modifying surgical facilities and techniques can be effective for preventing the development of POCD. Investigational therapies may offer novel strategies of treatments for POCD. Anesthetic preconditioning might be helpful for the improvement of POCD.

  • This study was carried out at The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People's Republic of China.
  • No financial support.

REFERENCES

  • 1
    Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, et al; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001;344(6):395-402.
  • 2
    Jungwirth B, Zieglgänsberger W, Kochs E, Rammes G. Anesthesia and postoperative cognitive dysfunction (POCD). Mini Rev Med Chem. 2009;9(14):1568-79.
  • 3
    Ge Y, Ma Z, Shi H, Zhao Y, Gu X, Wei H. Incidence and risk factors of postoperative cognitive dysfunction in patients underwent coronary artery bypass grafting surgery. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2014;39(10):1049-55.
  • 4
    Bryson GL, Wyand A, Wozny D, Rees L, Taljaard M, Nathan H. A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair. Can J Anaesth. 2011;58(3):246-55.
  • 5
    Otomo S, Maekawa K, Goto T, Baba T, Yoshitake A. Pre-existing cerebral infarcts as a risk factor for delirium after coronary artery bypass graft surgery. Interact Cardiovasc Thorac Surg. 2013;17(5):799-804.
  • 6
    McVeigh C, Passmore P. Vascular dementia: prevention and treatment. Clin Interv Aging. 2006;1(3):229-35.
  • 7
    Rundshagen I. Postoperative cognitive dysfunction. Dtsch Arztebl Int. 2014;111(8):119-25.
  • 8
    Habib S, Khan Au, Afridi MI, Saeed A, Jan AF, Amjad N. Frequency and predictors of cognitive decline in patients undergoing coronary artery bypass graft surgery. J Coll Physicians Surg Pak. 2014;24(8):543-8.
  • 9
    Laalou FZ, Carre AC, Forestier C, Sellal F, Langeron O, Pain L. Pathophysiology of post-operative cognitive dysfunction: current hypotheses. J Chir (Paris). 2008;145(4):323-30.
  • 10
    Polunina AG, Golukhova EZ, Guekht AB, Lefterova NP, Bokeria LA. Cognitive dysfunction after on-pump operations: neuropsychological characteristics and optimal core battery of tests. Stroke Res Treat. 2014;2014:302824.
  • 11
    van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012;67(3):280-93.
  • 12
    Zhang X, Dong H, Li N, Zhang S, Sun J, Zhang S, et al. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis. J Neuroinflammation. 2016;13(1):127.
  • 13
    Kudoh A, Takase H, Katagai H, Takazawa T. Postoperative interleukin-6 and cortisol concentrations in elderly patients with postoperative confusion. Neuroimmunomodulation. 2005;12(1):60-6.
  • 14
    Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med. 2012;366(3):250-7.
  • 15
    Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg. 1995;59(5):1289-95.
  • 16
    Saraçli Ö, Akca AS, Atasoy N, Önder Ö, Senormanci Ö, Kaygisiz I, et al. The relationship between quality of life and cognitive functions, anxiety and depression among hospitalized elderly patients. Clin Psychopharmacol Neurosci. 2015;13(2):194-200.
  • 17
    Helkala EL, Kivipelto M, Hallikainen M, Alhainen K, Heinonen H, Tuomilehto J, et al. Usefulness of repeated presentation of Mini-Mental State Examination as a diagnostic procedure: a population-based study. Acta Neurol Scand. 2002;106(6):341-6.
  • 18
    Jildenstål PK, Hallén JL, Rawal N, Berggren L. Does depth of anesthesia influence postoperative cognitive dysfunction or inflammatory response following major ENT surgery? J Anesth Clin Res. 2012;3(6):220.
  • 19
    Stroobant N, Van Nooten G, Belleghem Y, Vingerhoets G. Short-term and long-term neurocognitive outcome in on-pump versus off-pump CABG. Eur J Cardiothorac Surg. 2002;22(4):559-64.
  • 20
    Benabarre A, Vieta E, Martínez-Arán A, Garcia-Garcia M, Martín F, Lomeña F, et al. Neuropsychological disturbances and cerebral blood flow in bipolar disorder. Aust N Z J Psychiatry. 2005;39(4):227-34.
  • 21
    Proust-Lima C, Amieva H, Dartigues JF, Jacqmin-Gadda H. Sensitivity of four psychometric tests to measure cognitive changes in brain aging-population-based studies. Am J Epidemiol. 2007;165(3):344-50.
  • 22
    Reis HJ, Oliveira AC, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Yalvaç ME, et al. Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient. Cur Mol Med. 2014;14(9):1155-63.
  • 23
    Yuan SM. Biomarkers of cerebral injury in cardiac surgery. Anadolu Kardiyol Derg. 2014;14(7):638-45.
  • 24
    Kumpaitiene B, Svagzdiene M, Drigotiene I, Sirvinskas E, Sepetiene R, Zakelis R, et al. Correlation among decreased regional cerebral oxygen saturation, blood levels of brain injury biomarkers, and cognitive disorder. J Int Med Res. 22018;46(9):3621-9.
  • 25
    Thomaidou E, Argiriadou H, Vretzakis G, Megari K, Taskos N, Chatzigeorgiou G, et al. Perioperative use of erythromycin reduces cognitive decline after coronary artery bypass grafting surgery: a pilot study. Clin Neuropharmacol. 2017;40(5):195-200.
  • 26
    Kok WF, Koerts J, Tucha O, Scheeren TW, Absalom AR. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery. Anaesthesia. 2017;72(3):359-69.
  • 27
    Silva FP, Schmidt AP, Valentin LS, Pinto KO, Zeferino SP, Oses JP, et al. S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery: a prospective observational study. Eur J Anaesthesiol. 2016;33(9):681-9.
  • 28
    Öztürk S, Saçar M, Baltalarli A, Öztürk I. Effect of the type of cardiopulmonary bypass pump flow on postoperative cognitive function in patients undergoing isolated coronary artery surgery. Anatol J Cardiol. 2016;16(11):875-80.
  • 29
    Oldham MA, Hawkins KA, Yuh DD, Dewar ML, Darr UM, Lysyy T, et al. Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study. Int Psychogeriatr. 2015;27(12):1929-38.
  • 30
    Hassani S, Alipour A, Darvishi Khezri H, Firouzian A, Emami Zeydi A, Gholipour Baradari A, et al. Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl). 2015;232(5):843-50.
  • 31
    Dong S, Li CL, Liang WD, Chen MH, Bi YT, Li XW. Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery. Peptides. 2014;59:70-4.
  • 32
    Trubnikova OA, Mamontova AS, Syrova ID, Maleva OV, Barbarash OL. Does preoperative mild cognitive impairment predict postoperative cognitive dysfunction after on-pump coronary bypass surgery? J Alzheimers Dis. 2014;42(Suppl 3):S45-51.
  • 33
    Kok WF, van Harten AE, Koene BM, Mariani MA, Koerts J, Tucha O, et al. A pilot study of cerebral tissue oxygenation and postoperative cognitive dysfunction among patients undergoing coronary artery bypass grafting randomised to surgery with or without cardiopulmonary bypass. Anaesthesia. 2014;69(6):613-22.
  • 34
    Szwed K, Pawliszak W, Anisimowicz L, Bucinski A, Borkowska A. Short-term outcome of attention and executive functions from aorta no-touch and traditional off-pump coronary artery bypass surgery. World J Biol Psychiatry. 2014;15(5):397-403.
  • 35
    Fontes MT, McDonagh DL, Phillips-Bute B, Welsby IJ, Podgoreanu MV, Fontes ML, et al; Neurologic Outcome Research Group (NORG) of the Duke Heart Center. Arterial hyperoxia during cardiopulmonary bypass and postoperative cognitive dysfunction. J Cardiothorac Vasc Anesth. 2014;28(3):462-6.
  • 36
    Sirvinskas E, Usas E, Mankute A, Raliene L, Jakuska P, Lenkutis T, et al. Effects of intraoperative external head cooling on short-term cognitive function in patients after coronary artery bypass graft surgery. Perfusion. 2014;29(2):124-9.
  • 37
    Joung KW, Rhim JH, Chin JH, Kim WJ, Choi DK, Lee EH, et al. Effect of remote ischemic preconditioning on cognitive function after off-pump coronary artery bypass graft: a pilot study. Korean J Anesthesiol. 2013;65(5):418-24.
  • 38
    Mu DL, Li LH, Wang DX, Li N, Shan GJ, Li J, et al. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: a prospective cohort study. PLoS One. 2013;8(10):e77637.
  • 39
    Kadoi Y, Kawauchi C, Kuroda M, Takahashi K, Saito S, Fujita N, et al. Association between cerebrovascular carbon dioxide reactivity and postoperative short-term and long-term cognitive dysfunction in patients with diabetes mellitus. J Anesth. 2011;25(5):641-7.
  • 40
    de Tournay-Jetté E, Dupuis G, Bherer L, Deschamps A, Cartier R, Denault A. The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011;25(1):95-104.
  • 41
    Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, et al. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009;87(1):36-44.
  • 42
    Haljan G, Maitland A, Buchan A, Arora RC, King M, Haigh J, et al. The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial. Stroke. 2009;40(8):2769-75.
  • 43
    Silbert BS, Evered LA, Scott DA, Cowie TF. The apolipoprotein E epsilon4 allele is not associated with cognitive dysfunction in cardiac surgery. Ann Thorac Surg. 2008;86(3):841-7.
  • 44
    Jensen BØ, Rasmussen LS, Steinbrüchel DA. Cognitive outcomes in elderly high-risk patients 1 year after off-pump versus on-pump coronary artery bypass grafting. A randomized trial. Eur J Cardiothorac Surg. 2008;34(5):1016-21.
  • 45
    Hogue CW, Fucetola R, Hershey T, Freedland K, Dávila-Román VG, Goate AM, et al. Risk factors for neurocognitive dysfunction after cardiac surgery in postmenopausal women. Ann Thorac Surg. 2008;86(2):511-6.
  • 46
    Puskas F, Grocott HP, White WD, Mathew JP, Newman MF, Bar-Yosef S. Intraoperative hyperglycemia and cognitive decline after CABG. Ann Thorac Surg. 2007;84(5):1467-73.
  • 47
    Kadoi Y, Goto F. Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery. J Anesth. 2007;21(3):330-5.
  • 48
    Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery. Surg Today. 2006;36(12):1053-7.
  • 49
    Jensen BO, Hughes P, Rasmussen LS, Pedersen PU, Steinbrüchel DA. Cognitive outcomes in elderly high-risk patients after off-pump versus conventional coronary artery bypass grafting: a randomized trial. Circulation. 2006;113(24):2790-5.
  • 50
    Silbert BS, Scott DA, Evered LA, Lewis MS, Kalpokas M, Maruff P, et al. A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly. Anesthesiology. 2006;104(6):1137-45.
  • 51
    Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg. 2002;95(5):1134-41.
  • 52
    Aykut K, Albayrak G, Guzeloglu M, Hazan E, Tufekci M, Erdogan I. Pulsatile versus non-pulsatile flow to reduce cognitive decline after coronary artery bypass surgery: a randomized prospective clinical trial. J Cardiovasc Dis Res. 2013;4(2):127-9.
  • 53
    Undar A, Eichstaedt HC, Bigley JE, Deady BA, Porter AE, Vaughn WK, et al. Effects of pulsatile and nonpulsatile perfusion on cerebral hemodynamics investigated with a new pediatric pump. J Thorac Cardiovasc Surg. 2002;124(2):413-6.
  • 54
    Hickey PR, Buckley MJ, Philbin DM. Pulsatile and nonpulsatile cardiopulmonary bypass: review of a counterproductive controversy. Ann Thorac Surg. 1983;36(6):720-37.
  • 55
    Koning NJ, Vonk AB, van Barneveld LJ, Beishuizen A, Atasever B, van den Brom CE, et al. Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics. J Appl Physiol (1985). 2012;112(10):1727-34.
  • 56
    O'Neil MP, Fleming JC, Badhwar A, Guo LR. Pulsatile versus nonpulsatile flow during cardiopulmonary bypass: microcirculatory and systemic effects. Ann Thorac Surg. 2012;94(6):2046-53.
  • 57
    Lee JD, Lee SJ, Tsushima WT, Yamauchi H, Lau WT, Popper J, et al. Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial. Ann Thorac Surg. 2003;76(1):18-25.
  • 58
    Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg. 2000;69(4):1162-6.
  • 59
    Zamvar V, Williams D, Hall J, Payne N, Cann C, Young K, et al. Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial. BMJ. 2002;325(7375):1268.
  • 60
    Emmert MY, Seifert B, Wilhelm M, Grünenfelder J, Falk V, Salzberg SP. Aortic no-touch technique makes the difference in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2011;142(6):1499-506.
  • 61
    Taggart DP, Browne SM, Halligan PW, Wade DT. Is cardiopulmonary bypass still the cause of cognitive dysfunction after cardiac operations? J Thorac Cardiovasc Surg. 1999;118(3):414-20.
  • 62
    Vedin J, Nyman H, Ericsson A, Hylander S, Vaage J. Cognitive function after on or off pump coronary artery bypass grafting. Eur J Cardiothorac Surg. 2006;30(2):305-10.
  • 63
    Van Dijk D, Jansen EW, Hijman R, Nierich AP, Diephuis JC, Moons KG, et al; Octopus Study Group. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA. 2002;287(11):1405-12.
  • 64
    van Dijk D, Moons KG, Keizer AM, Jansen EW, Hijman R, Diephuis JC, et al; Octopus Study Group. Association between early and three month cognitive outcome after off-pump and on-pump coronary bypass surgery. Heart. 2004;90(4):431-4.
  • 65
    Beratis IN, Papageorgiou SG. Heart surgery and the risk of cognitive decline. Arch Hellenic Med. 2014;31(2):186-90.
  • 66
    Colak Z, Borojevic M, Bogovic A, Ivancan V, Biocina B, Majeric-Kogler V. Influence of intraoperative cerebral oximetry monitoring on neurocognitive function after coronary artery bypass surgery: a randomized, prospective study. Eur J Cardiothorac Surg. 2015;47(3):447-54.
  • 67
    Hammon JW, Stump DA, Butterworth JF, Moody DM, Rorie K, Deal DD, et al. Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: the effect of reduced aortic manipulation. J Thorac Cardiovasc Surg. 2006;131(1):114-21.
  • 68
    Ates M, Yangel M, Gullu AU, Sensoz Y, Kizilay M, Akcar M. Is single or double aortic clamping safer in terms of cerebral outcome during coronary bypass surgery? Int Heart J. 2006;47(2):185-92.
  • 69
    Whitaker DC, Stygall J, Newman SP. Neuroprotection during cardiac surgery: strategies to reduce cognitive decline. Perfusion. 2002;17(Suppl):69-75.
  • 70
    Raja PV, Blumenthal JA, Doraiswamy PM. Cognitive deficits following coronary artery bypass grafting: prevalence, prognosis, and therapeutic strategies. CNS Spectr. 2004;9(10):763-72.
  • 71
    Royse CF, Andrews DT, Newman SN, Stygall J, Williams Z, Pang J, et al. The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery. Anaesthesia. 2011;66(6):455-64.
  • 72
    Piriou V, Chiari P, Gateau-Roesch O, Argaud L, Muntean D, Salles D, et al. Desflurane-induced preconditioning alters calcium-induced mitochondrial permeability transition. Anesthesiology. 2004;100(3):581-8.
  • 73
    Wei H, Inan S. Dual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis. Prog Neuropsychopharmacol Biol Psychiatry. 2013;47:156-61.
  • 74
    Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, et al. Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg. 2003;97(3):718-40.
  • 75
    Zhou C, Liu J, Chen XD. General anesthesia mediated by effects on ion channels. World J Crit Care Med. 2012;1(3):80-93.

Publication Dates

  • Publication in this collection
    Jan-Feb 2019

History

  • Received
    06 June 2018
  • Accepted
    21 Sept 2018
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