Brain injury after adult cardiac surgery
Corresponding Author
J. Ahonen
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland
Jouni Ahonen Department of Anaesthesia Women's Hospital PO Box 140 FIN-00029 HUS Finland e-mail: [email protected]Search for more papers by this authorM. Salmenperä
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorCorresponding Author
J. Ahonen
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland
Jouni Ahonen Department of Anaesthesia Women's Hospital PO Box 140 FIN-00029 HUS Finland e-mail: [email protected]Search for more papers by this authorM. Salmenperä
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland
Search for more papers by this authorAbstract
Despite remarkable progress in surgical, cardiopulmonary bypass and anaesthetic techniques during the last three decades, brain damage remains an important complication of adult cardiac surgery. Effective brain protection strategies are already implemented today, but ongoing research is needed to meet the challenges faced in operating on increasingly old and disabled patients. The incidence of brain injury may be reduced by modifying the surgical procedure according to carotid duplex scanning and epiaortic echocardiography, by using techniques to reduce microembolization during cardiopulmonary bypass and by optimizing patient temperature during and after surgery. Increased knowledge will aid in choosing the best procedure or combination of procedures in each case to ensure that risks do not outweigh benefits.
References
- 1 Lillehei CW. Historical development of cardiopulmonary bypass. In: GB Gravlee, RF Davis, JR Utley, eds. Cardiopulmonary bypass: Principles and practice. Baltimore: Williams & Wilkins, 1993; 1–26.
- 2 Taylor KM. Cardiac surgery and the brain: an introduction. In: PL Smith, KM Taylor, eds. Cardiac surgery and the brain. London: Edward Arnold, 1993; 1–14.
- 3 Eagle KA, Guyton RA, Davidoff R et al. ACC/AHA guidelines for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1991 guidelines for coronary artery bypass graft surgery). J Am Coll Cardiol 1999; 34: 1262–347.
- 4 Taylor KM. Brain damage during cardiopulmonary bypass. Ann Thorac Surg 1998; 65: S20–6.
- 5 Murkin JM. Central nervous system dysfunction after cardiopulmonary bypass. In: JA Kaplan, ed. Cardiac anesthesia. Philadelphia: W. B. Saunders Company, 1999; 1259–79.
- 6 Kuroda Y, Uchimoto R, Kaieda R et al. Central nervous system complications after cardiac surgery: a comparison between coronary artery bypass grafting and valve surgery. Anesth Analg 1993; 76: 222–7.
- 7 Slogoff S, Girgis KZ, Keats AS. Etiologic factors in neuropsychiatric complications associated with cardiopulmonary bypass. Anesth Analg 1982; 61: 903–11.
- 8 Amory DW, Grigore A, Amory JK et al. Neuroprotection is associated with α-adrenergic receptor antagonists during cardiac surgery: evidence from 2575 patients. J Cardiothorac Vasc Anesth 2002; 16: 270–7.
- 9 Gansera B, Angelis I, Weingartner J, Neumaier-Prauser P, Spiliopoulos K, Kemkes BM. Simultaneous carotid endarterectomy and cardiac surgery – additional risk factor or safety procedure? Thorac Cardiovasc Surg 2003; 51: 22–7.
- 10 Roach GW, Kanchuger M, Mora Mangano C et al., for The Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. Adverse cerebral outcomes after coronary bypass surgery. N Engl J Med 1996; 335: 1857–63.
- 11 Puskas JD, Winston D, Wright CE et al. Stroke after coronary artery operation. Incidence, correlates, outcome, and cost. Ann Thorac Surg 2000; 69: 1053–6.
- 12 Salazar JD, Wityk RJ, Grega MA et al. Stroke after cardiac surgery. Short- and long-term outcomes. Ann Thorac Surg 2001; 72: 1195–202.
- 13 Ergin MA, Galla JD, Lansman SL, Quintana C, Bodian C, Griepp RB. Hypothermic circulatory arrest in operations of the thoracic aorta. Determinants of operative mortality and neurologic outcome. J Thorac Cardiovasc Surg 1994; 107: 788–97.
- 14 Ergin MA, Griepp EB, Lansman SL, Galla JD, Levy M, Griepp RB. Hypothermic circulatory arrest and other methods of cerebral protection during operations on the thoracic aorta. J Card Surg 1994; 9: 525–37.
- 15 Davis EA, Gillinov AM, Cameron DE, Reitz BA. Hypothermic circulatory arrest as a surgical adjunct: a 5-year experience with 60 adult patients. Ann Thorac Surg 1992; 53: 402–6.
- 16 Van Der Mast RC, Roest FHJ. Delirium after cardiac surgery: a critical review. J Psychosom Res 1996; 41: 13–30.
- 17 Van Der Mast RC, Van Den Broek WW, Fekkes D, Pepplinkhuizen L, Habbema JDF. Incidence of and preoperative predictors for delirium after cardiac surgery. J Psychosom Res 1999; 46: 479–83.
- 18 Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM. Neuropsychologic change after cardiac surgery: a critical review. J Cardiothorac Vasc Anesth 1996; 10: 105–12.
- 19 Moller JT, Cluitmans P, Rasmussen LS et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD 1 study. Lancet 1998; 351: 857–61.
- 20 Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery. A five-year neuropsychological follow-up study. Stroke 1986; 17: 410–6.
- 21 Newman MF, Kirchner JL, Phillips-Bute B et al., for the 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: 395–402.
- 22 Oxman TE, Freeman DH, Manheimer DE. Lack of social participation or religious strength and comfort as risk factors for death after cardiac surgery in the elderly. Psychosom Med 1995; 57: 5–15.
- 23 Frasure-Smith N, Prince R. The ischemic heart disease life stress monitoring program: impact on mortality. Psychosom Med 1985; 47: 431–45.
- 24 Milani RV, Lavie CJ. Prevalence and effects of cardiac rehabilitation on depression in the elderly with coronary heart disease. Am J Cardiol 1998; 81: 1233–6.
- 25 Barbut D, Grassineau D, Lis E, Heier L, Hartman GS, Isom OW. Posterior distribution of infarcts in strokes related to cardiac operations. Ann Thorac Surg 1998; 65: 1656–9.
- 26 Wityk RJ, Goldsborough MA, Hillis A et al. Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients with neurologic complications after cardiac surgery. Arch Neurol 2001; 58: 571–6.
- 27 Beauchamp NJ Jr, Bryan RN. Acute cerebral ischemic infarction: a pathophysiologic review and radiologic perspective. AJR Am J Roentgenol 1998; 171: 73–84.
- 28 Hansotia PL, Myers WO, Ray JF, Greehling S, Sautter RD. Prognostic value of electroencephalography in cardiac surgery. Ann Thorac Surg 1975; 19: 127–34.
- 29 Arrowsmith JE, Grocott HP, Reves JG, Newman MF. Central nervous system complications of cardiac surgery. Br J Anaesth 2000; 84: 378–93.
- 30 Anderson R, Hansson L-O, Liska J, Settergren G, Vaage J. The effect of the cardiotomy suction on the brain injury marker S100β after cardiopulmonary bypass. Ann Thorac Surg 2000; 69: 847–50.
- 31 Anderson R, Hansson L-O, Dijlai-Merzoug R, Settergren G. High serum S100β levels for trauma patients without head injuries. Neurosurgery 2001; 48: 1255–8.
- 32 Johnsson P, Lundqvist C, Lindgren A, Ferencz I, Alling C, Ståhl E. Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood. J Cardiothorac Vasc Anesth 1995; 9: 694–9.
- 33 Westaby S, Johnsson P, Parry AJ et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg 1996; 61: 88–92.
- 34 Soinne L, Roine RO. Blood tests for cognitive decline? Acta Anaesthesiol Scand 1999; 43: 491–3.
- 35 Newman MF, Croughwell ND, Blumenthal JA et al. Association with postoperative cognitive dysfunction. Circulation 1994; 90: II243–9.
- 36 Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995; 59: 1289–95.
- 37 Murkin JM, Stump DA, Blumenthal JA, McKhann G. Defining dysfunction: group means versus incidence analysis – a statement of consensus. Ann Thorac Surg 1997; 64: 904–5.
- 38 Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth 1998; 81: 449–62.
- 39 Harris DNF, Bailey SM, Smith PLC, Taylor KM, Oatridge A, Bydder GM. Brain swelling in first hour after coronary artery bypass surgery. Lancet 1993; 342: 586–7.
- 40 Anderson RE, Li T-Q, Hindmarsch T, Settergren T, Vaage J. Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery. J Cardiothorac Vasc Anesth 1999; 13: 698–702.
- 41 Harris DNF, Oatridge A, Dob D, Smith PLC, Taylor KM, Bydder GM. Cerebral swelling after normothermic cardiopulmonary bypass. Anesthesiology 1998; 88: 340–5.
- 42 Hindman BJ, Funatsu N, Cheng DC, Bolles R, Todd MM, Tinker JH. Differential effect of oncotic pressure on cerebral and extracerebral water content during cardiopulmonary bypass in rabbits. Anesthesiology 1990; 73: 951–7.
- 43 Drew PA, Smith E, Thomas PD. Fat distribution and changes in the blood–brain barrier in a rat model of cerebral arterial fat embolism. J Neurol Sci 1998; 156: 138–43.
- 44 Blauth CI, Arnold JV, Schulenberg JV, McCartney AC, Taylor KM. Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988; 95: 668–76.
- 45 Pugsley W, Klinger L, Paschalis C, Treasure T, Harrison M, Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994; 25: 1393–9.
- 46 Sylivris S, Levi C, Matalanis G et al. Pattern and significance of cerebral microemboli during coronary artery bypass grafting. Ann Thorac Surg 1998; 66: 1674–8.
- 47 Brækken SK, Russel D, Brucher R, Abdelnoor M, Svennevig JL. Cerebral microembolic signals during cardiopulmonary bypass surgery. Frequency, time of occurrence, and association with patient and surgical characteristics. Stroke 1997; 28: 1988–92.
- 48 Taggart DP, Bhattacharya K, Meston N et al. Serum S-100 protein concentration after cardiac surgery: a randomized trial of arterial line filtration. Eur J Cardiothorac Surg 1997; 11: 645–9.
- 49 Moody DM, Bell MA, Challa VR, Johnston WE, Prough DS. Brain microemboli during cardiac surgery or aortography. Ann Neurol 1990; 28: 477–86.
- 50 Brooker RF, Brown WR, Moody DM et al. Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary bypass. Ann Thorac Surg 1998; 65: 1651–5.
- 51 Kincaid EH, Jones TJ, Stump DA et al. Processing scavenged blood with a cell saver reduces cerebral lipid microembolization. Ann Thorac Surg 2000; 70: 1296–300.
- 52 Brown WR, Moody DM, Challa VR, Stump DA, Hammon JW. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke 2000; 31: 707–13.
- 53 Eherenfeld WK, Hoyt WF, Wylie EJ. Embolization and transient blindness from carotid atheroma: surgical considerations. Arch Surg 1966; 93: 787–94.
- 54 Kamenar E, Burger P. Cerebral fat embolism: a neuropathological study of microembolic state. Stroke 1980; 11: 477–84.
- 55 Takahashi M, Suzuki R, Osakabe Y et al. Magnetic resonance imaging findings in cerebral fat embolism: Correlation with clinical manifestations. J Trauma 1999; 46: 324–7.
- 56 Fox LS, Blackstone EH, Kirklin JW, Stewart RW, Samuelson PN. Relationship of whole-body oxygen consumption to perfusion flow rate during hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 1982; 83: 239–48.
- 57 Mankovsky BN, Piolot R, Mankovsky OL, Ziegler D. Impairment of cerebral autoregulation in diabetic patients with cardiovascular neuropathy and orthostatic hypotension. Diabet Med 2003; 20: 119–26.
- 58 Croughwell N, Lyth M, Quill TJ et al. Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass. Circulation 1990; 82: IV407–, 12.
- 59 Astrup J, Symon L, Branston NM, Lassen NA. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 1977; 8: 51–7.
- 60 Patel RL, Turtle MR, Chambers DJ, James DN, Newman S, Venn GE. Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996; 111: 1267–79.
- 61 Stephan H, Weyland A, Kazmaier S, Henze T, Menck S, Sonntag H. Acid-base management during hypothermic cardiopulmonary bypass does not affect cerebral metabolism but does affect blood flow and neurological outcome. Br J Anaesth 1992; 69: 51–7.
- 62 Murkin JM, Martzke JS, Buchan AM, Bentley C, Wong CJ. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 1995; 110: 349–62.
- 63 Engelhardt W, Dierks T, Pause M, Hartung E. Early cerebral functional outcome after coronary artery bypass surgery using different acid-base management during hypothermic cardiopulmonary bypass. Acta Anaesthesiol Scand 1996; 40: 457–65.
- 64 Kern FH, Hickey PR. The effect of cardiopulmonary bypass on the brain. In: RA Jonas, M Elliott, eds. Cardiopulmonary bypass in neonates, infants, and young children. Oxford: Butterworth-Heineman, 1994; 263–81.
- 65 Bennett-Guerrero E. Systemic inflammation. In: JA Kaplan, ed. Cardiac anesthesia. Philadelphia: W. B. Saunders Company, 1999; 297–318.
- 66 Helps SC, Gorman DF. Air embolism of the brain in rabbits pretreated with mechlorethamine. Stroke 1991; 22: 351–4.
- 67 Reasoner DK, Hindman BJ, Dexter F, Subieta A, Cutkomp J, Smith T. Doxycycline reduces early neurologic impairment after cerebral arterial air embolism in the rabbit. Anesthesiology 1997; 87: 569–76.
- 68 Abramov D, Tamariz MG, Sever JY et al. The influence of gender on the outcome of coronary artery bypass surgery. Ann Thorac Surg 2000; 70: 800–6.
- 69 Jacobs AK, Kelsey SF, Mori Brooks M et al. Better outcome for women compared with men undergoing coronary revascularization. A report from the Bypass Angioplasty Revascularization Investigation (BARI). Circulation 1998; 98: 1279–85.
- 70 Hogue CW, Murphy SF, Schechtman KB, Dávila-Román VG. Risk factors for early or delayed stroke after cardiac surgery. Circulation 1999; 100: 642–7.
- 71 Blauth CI, Cosgrove DM, Webb BW et al. Atheroembolism from the ascending aorta. An emerging problem in cardiac surgery. J Thorac Cardiovasc Surg 1992; 103: 1104–12.
- 72 Ura M, Sakata R, Nakayama Y, Goto T. Ultrasonographic demonstration of manipulation-related aortic injuries after cardiac surgery. J Am Coll Cardiol 2000; 35: 1303–10.
- 73 Dávila-Román VG, Phillips KJ, Daily BB, Dávila R, Kouchoukos NT, Barzilai B. Intraoperative transesophageal echogardiography and epiaortic ultrasound for assessment of atherosclerosis of the thoracic aorta. J Am Coll Cardiol 1996; 28: 942–7.
- 74 Wareing TH, Dávila-Román VG, Daily BB et al. Strategy for the reduction of stroke incidence in cardiac surgical patients. Ann Thorac Surg 1993; 55: 1400–8.
- 75 Katz ES, Tunick PA, Rusinek H, Ribakove G, Spencer FC, Kronzon I. Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol 1992; 20: 70–7.
- 76 Gaudino M, Glieca F, Alessandrini F et al. Individualized surgical strategy for the reduction of stroke risk in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 1999; 67: 1246–53.
- 77 Royse AG, Royse CF, Ajani AE et al. Reduced neuropsychological dysfunction using epiaortic echocardiography and the exclusive Y graft. Ann Thorac Surg 2000; 69: 1431–8.
- 78 D'Agostino RS, Svensson LG, Neumann DJ, Balkhy HH, Williamson WA, Shabian DM. Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients. Ann Thorac Surg 1996; 62: 1714–23.
- 79 Berens ES, Kouchoukos NT, Murphy SF, Wareing TH. Preoperative carotid artery screening in elderly patients undergoing cardiac surgery. J Vasc Surg 1992; 15: 313–21.
- 80 Schwartz LB, Bridgman AH, Kieffer RW et al. Asymptomatic carotid artery stenosis and stroke in patients undergoing cardiopulmonary bypass. J Vasc Surg 1995; 21: 146–53.
- 81 Salasidis GC, Latter DA, Steinmetz OK, Blair JF, Graham AM. Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke. J Vasc Surg 1995; 21: 154–60.
- 82 Rizzo RJ, Whittemore AD, Couper GS et al. Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath. Ann Thorac Surg 1992; 54: 1099–108.
- 83 Anon. Endarterectomy for asymptomatic carotid artery stenosis: executive committee for the asymptomatic carotid atherosclerosis study. JAMA 1995; 273: 1421–8.
- 84 Anon. Endarterectomy for moderate symptomatic carotid stenosis: interim results from the MRC European carotid surgery trial. Lancet 1996; 347: 1591–3.
- 85 Akins CW, Moncure AC, Daggett WM et al. Safety and efficacy of concomitant carotid and coronary artery operations. Ann Thorac Surg 1995; 60: 311–7.
- 86 Hertzer NR, Loop FD, Beven EG, O'Hara PJ, Krajewski LP. Surgical staging for simultaneous coronary and carotid disease: a study including prospective randomization. J Vasc Surg 1989; 9: 455–63.
- 87 Mathew JP, Parks R, Savino JS et al. Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. Multi-Center Study of Perioperative Ischemia Research Group. JAMA 1996; 276: 300–6.
- 88 Stanley TO, Mackensen B, Grocott HP et al., The Neurologic Outcome Research Group, and The CARE Investigators of the Duke Heart Center. The impact of postoperative atrial fibrillation on neurocognitive outcome after coronary artery bypass graft surgery. Anesth Analg 2002; 94: 290–5.
- 89 Cox JL. A perspective of postoperative atrial fibrillation in cardiac patients. Ann Thorac Surg 1993; 56: 405–9.
- 90 Keren A, Goldberg S, Gottlieb S et al. Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. J Am Coll Cardiol 1990; 15: 790–800.
- 91 McKhann GM, Borowicz LM, Goldsborough MA, Enger C, Selnes OA. Depression and cognitive decline after coronary artery bypass grafting. Lancet 1997; 349: 1282–4.
- 92 Edwardson J, Morris C. The genetics of Alzheimer's disease. BMJ 1998; 317: 361–2.
- 93 Tardiff BE, Newman MF, Saunders AM et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. Ann Thorac Surg 1997; 64: 715–20.
- 94 Steed L, Kong R, Stygall J et al. The role of apolipoprotein E in cognitive decline after cardiac operation. Ann Thorac Surg 2001; 71: 823–6.
- 95 Mathew JP, Rinder CS, Howe JG et al., and the Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Platelet P1A2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass. Ann Thorac Surg 2001; 71: 663–6.
- 96 Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PlA1/A2 polymorphism of platelet GP IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 1997; 349: 385–8.
- 97 Zotz RB, Winkelmann BR, Nauck M et al. Polymorphism of platelet membrane GP IIIa: human platelet antigen 1b (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in coronary artery disease. Thromb Hemost 1998; 79: 731–5.
- 98 Svensson LG, Crawford ES, Hess KR et al. Deep hypothermia with circulatory arrest: determinants of stroke and early mortality in 656 patients. J Thorac Cardiovasc Surg 1993; 106: 19–28.
- 99 DeBakey ME, Cooley DA, Crawford ES. Successful resection of fusiform aneurysm of aortic arch with replacement by homografts. Surg Gyncol Obstet 1957; 105: 656.
- 100 Mills NL, Ochsner JL. Massive air embolism during cardiopulmonary bypass: causes, prevention, and management. J Thorac Cardiovasc Surg 1980; 80: 708–17.
- 101 Ueda Y, Miki S, Kusuhara K, Okita Y, Tahata T, Yamanaka K. Deep hypothermic systemic circulatory arrest and continuous retrograde cerebral perfusion for surgery of aortic arch aneurysm. Eur J Cardiothorac Surg 1992; 6: 36–41.
- 102 Griepp RB, Ergin MA, McCullough JN et al. Use of hypothermic circulatory arrest for cerebral protection during aortic surgery. J Card Surg 1997; 12: 312–21.
- 103 Juvonen T, Weisz DJ, Wolfe D et al. Can retrograde perfusion mitigate cerebral injury following particulate embolization? J Thorac Cardiovasc Surg 1998; 115: 1142–59.
- 104 Grigore AM, Mathew J, Grocott HP et al. Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery. Anesthesiology 2001; 95: 1110–9.
- 105 Martin TD, Craver JM, Gott JP et al. Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. Ann Thorac Surg 1994; 57: 298–302.
- 106 Nathan HJ, Wells GA, Munson JL, Wozny D. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass. Circulation 2001; 104 (Suppl. 1): 85–91.
- 107 Grigore AM, Grocott HP, Mathew J et al., and the Neurologic Outcome Research Group of the Duke Heart Center. The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg 2002; 94: 4–10.
- 108 Ginsberg MD, Sternau LL, Globus MY, Dietrich WD, Busto R. Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev 1992; 4: 189–225.
- 109 Nemoto EM, Klementavicius R, Melick JA, Yonas H. Suppression for cerebral metabolic rate for oxygen (CMRO2) by mild hypothermia compared with thiopental. J Neurosurg Anesthesiol 1996; 8: 52–9.
- 110 Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 1989; 20: 904–10.
- 111 Jones TJ, Stump DA, Deal DD, Vernon JC, Manuel JC. Hypothermia protects the brain from embolization by reducing and redirecting the embolic load. (Abstract). Ann Thorac Surg 1999; 68: 1465.
- 112 Grocott HP, Mackensen B, Grigore AM et al., and the Neurologic Outcome Research Group (NORG), and Cardiothoracic Anesthesiology Research Endeavors (CARE) Investigators of the Duke Heart Center. Postoperative hyperthermia is associated with cognitive dysfunction after coronary artery bypass graft surgery. Stroke 2002; 33: 537–41.
- 113 Shum-Tim D, Nagashima M, Shinoka T et al. Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg 1998; 116: 780–92.
- 114 Castillo J, Davalos A, Marrugat J, Noya M. Timing for fever-related brain damage in acute ischemic stroke. Stroke 1998; 29: 2455–60.
- 115 Mora Mangano C, Hill L, Cartwright CR, Hindman BJ. Cardiopulmonary bypass and the anesthesiologist. In: JA Kaplan, ed. Cardiac anesthesia. Philadelphia: W. B. Saunders Company, 1999; 1061–110.
- 116 Gold JP, Charlson ME, Williams-Russo P et al. Improvement of outcomes after coronary artery bypass: a randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 1995; 110: 1302–11.
- 117 Van Wermeskerken GK, Lardenoye J-WH, Hill SE et al. Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome. Ann Thorac Surg 2000; 69: 1077–83.
- 118 Plöchl W, Krenn CG, Cook DJ et al. Can hypocapnia reduce cerebral embolization during cardiopulmonary bypass? Ann Thorac Surg 2001; 72: 845–9.
- 119 Sieber FE, Traystman RJ. Special issues: glucose and the brain. Crit Care Med 1992; 20: 104–14.
- 120 Guyton RA, Mellitt RJ, Weintraub WS. A critical assessment of neurological risk during warm heart surgery. J Card Surg 1995; 10: 488–92.
- 121 Van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359–67.
- 122 Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000; 355: 773–8.
- 123 Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesthesiology 1986; 64: 165–70.
- 124 Zaidan JR, Klochany A, Martin W. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology 1991; 74: 406–14.
- 125 Roach GW, Newman MF, Murkin JM et al. Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Anesthesiology 1999; 90: 1255–64.
- 126 Newman MF, Murkin JM, Roach G et al. Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Anesth Analg 1995; 81: 452–7.
- 127 Kudo M, Aono M, Lee Y, Massey G, Pearlstein RD, Warner DS. Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures. Anesthesiology 2001; 95: 756–65.
- 128 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: 1134–41.
- 129 Legault C, Furberg CD, Wagenknecht LE et al. Nimodipine neuroprotection in cardiac valve replacement: Report of an early terminated trial. Stroke 1996; 27: 593–8.
- 130 Mullane K, Bullough D, Shapiro D. From academic vision to clinical reality: a case study of acadesine. Trends Cardiovasc Med 1993; 3: 227–34.
- 131 Mangano DT. Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group. JAMA 1997; 277: 325–32.
- 132 Anttila V, Rimpiläinen J, Pokela M et al. Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model. J Thorac Cardiovasc Surg 2000; 120: 247–55.
- 133 Arrowsmith JE, Harrison MJG, Newman SP, Stygall J, Timberlake N, Pugsley WB. Neuroprotection of the brain during cardiopulmonary bypass. A randomized trial of remacemide during coronary artery bypass in 171 patients. Stroke 1998; 29: 2357–62.
- 134 Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 2002; 54: 271–84.
- 135 Ferguson TB, Coombs LP, Peterson ED. Preoperative α-blocker use and mortality and morbidity following CABG surgery in North America. JAMA 2002; 287: 2221–7.
- 136 Gott JP, Cooper WA, Schmidt FE Jr et al. Modifying risk for extracorporeal circulation: Trial of four antiinflammatory strategies. Ann Thorac Surg 1998; 66: 747–54.
- 137 Westaby S, Saatvedt K, White S, Katsumata T, Van Oeveren W, Halligan PW. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass? Ann Thorac Surg 2001; 71: 667–72.
- 138 Reichenspurner H, Navia JA, Berry G et al. Particulate emboli capture by an intra-aortic filter device during cardiac surgery. J Thorac Cardiovasc Surg 2000; 119: 233–41.
- 139 Bergman P, Hadjinikolaou L, Van Der Linden J. Aortic atheroma is related to number of particulates captured by intra-aortic filtration in CABG. Eur J Cardiothorac Surg 2002; 22: 539–44.
- 140 Taggart D. About impaired minds and closed hearts. Off-pump coronary artery bypass grafting may be associated with lesser postoperative neurocognitive impairment. BMJ 2002; 325: 1255–6.
- 141 Van Dijk D, Jansen EWL, Hijman R et al. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery. JAMA 2002; 287: 1405–12.
- 142 Mark DB, Newman MF. Protecting the brain in coronary artery bypass graft surgery. JAMA 2002; 287: 1448–50.
- 143 Zamvar V, Williams D, Hall J et al. Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomized controlled trial. BMJ 2002; 325: 1268–71.
- 144 Ahonen J, Roine RO, Rämö J, Salmenperä M. Brain complications of heart surgery in adults. (Finnish) Duodecim. 2002; 118: 1957–65.