Neurologic dysfunction remains the most significant complication associated with cardiopulmonary bypass (CPB). The insidious change of cognitive decline has been perceived as a key factor that has contributed to the shift to percutaneous intervention for coronary disease. Current neuropsychologic testing provides the most sensitive means of demonstrating clinically relevant cerebral damage of this nature. Through extensive experience in randomized clinical trials of over 900 patients undergoing CPB, our team has addressed several key hypotheses related to the embolic/ischemic nature of cerebral injury in cardiac surgery, using this testing. In the first temperature study, patients randomized to hypothermia with passive re-warming had a lower incidence of neurocognitive deficit when compared with those patients who were actively re-warmed to 37°. In order to clarify the role of the hypothermia as opposed to the re-warming process, a second temperature study was completed. In the hypothermic group, patients were cooled and maintained at 34° with no active re-warming whereas, in the normothermic group, the patients were kept at 37° throughout the perioperative period. No difference in neurocognitive outcome in the two groups was seen, implying that the benefit seen in the first temperature study was related not to the hypothermia, but rather to the absence of active re-warming. In the cardiotomy study, patients were randomized to either a control group in which their cardiotomy blood was returned unprocessed, or a treatment group in which this blood was sequestered and processed with centrifugal washing and fat filtration. No significant difference in neurocognitive outcome was found in these two groups. On the other hand, there was a significant increase in bleeding and transfusion requirements in the treatment group. Many of our daily practices in CPB management are based upon assumptions from observational studies without sound reference to evidence-based medicine. Our recent studies have challenged our assumptions related to ischemia and embolic events during CPB. They have also confirmed that, when high standards in trial design are applied, the results can have universal implications in terms of our practice.Perfusion (2007) 22, 153—160.
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References
1.
Kassell NF, Dumont ASRandomized controlled trials in surgery: comic opera no more?J Thorac Cardiovasc Surg2006; 132: 243—44.
2.
Horton R.Surgical research or comic opera: questions, but few answers. Lancet1996; 347: 984—85.
3.
Loop FD, Lytle BW, Cosgrove DM et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med1986 ; 314: 1—6.
4.
Anyanwu AC, Treasure T.Surgical research revisited: clinical trials in the cardiothoracic surgical literature. Eur J Cardiothorac Surg2004; 25: 299—303.
5.
Tiruvoipati R., Balasubramanian SP, Atturu G. et al. Improving the quality of reporting randomized controlled trials in cardiothoracic surgery: the way forward. J Thorac Cardiovasc Surg2006; 132: 233—40.
6.
Schulz KF, Chalmers I., Hayes RJ et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA1995; 273: 408—12.
7.
Rubens FD, Dupuis JY, Robblee J. et al. Feasibility of blinding in a randomized controlled trial comparing preoperative autologous donation and acute normovolemic hemodilution in adult cardiac surgery. Transfusion2000; 40: 1—5.
8.
Roach GW, Kanchuger M., Mangano CM et al. Adverse cerebral outcomes after coronary bypass surgery. NEJM1996; 335: 1857—63.
9.
Mahanna EP, Blumenthal JA, White WD et al. Defining neuropsychological dysfunction after coronary artery bypass grafting. Ann Thorac Surg1996; 61: 1342—47.
10.
Shaw PJ, Bates D., Cartlidge EF et al. Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery . Stroke1987; 18: 700—7.
11.
Newman S., Smith P., Treasure T.Acute neuropsychological consequences of coronary artery bypass surgery. Curr Psychol Res Rev1987; 6: 115—24.
12.
Kolkka R., Hilberman M.Neurologic dysfunction following cardiac operation with low-flow, low-pressure cardiopulmonary bypass. J Thorac Cardiovasc Surg1980; 79: 432—7.
13.
Newman MF, Kirchner JL, Phillips-Bute B. et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. NEJM2001; 344: 395—402.
14.
Selnes OA, Royall RM, Grega MA et al. Cognitive changes 5 years after coronary artery bypass grafting: is there evidence of late decline? Arch Neurol2001; 58: 598—604.
15.
Stygall J., Newman SP, Fitzgerald G. et al. Cognitive change 5 years after coronary artery bypass surgery . Health Psychol2003; 22: 579—86.
16.
Barone FC, Feuerstein GZ, White RFBrain cooling during transient focal ischemia provides complete neuroprotection . Neurosci Biobehav Rev1997; 21: 31—44.
17.
Hypothermia after Cardiac Arrest Study Group.Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med2002; 346: 549—56.
18.
Martin TD, Craver JM, Gott JP et al. Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. Ann Thorac Surg1994; 57: 298—302.
19.
Christakis GT, Koch JP, Deemar KA et al. A randomized study of the systemic effects of warm heart surgery [see comments]. Ann Thorac Surg1992; 54: 449—57.
20.
McLean RF, Wong BI, Naylor CD et al. Cardiopulmonary bypass, temperature, and central nervous system dysfunction. Circulation1994; 90(Pt 2): II-250.
21.
Engelman RM , Pleet AB, Rousou JA et al. Influence of cardiopulmonary bypass perfusion temperature on neurologic and hematologic function after coronary artery bypass grafting. Ann Thorac Surg1999 ; 67: 1547—55.
22.
Plourde G., Leduc AS, Morin JE et al. Temperature during cardiopulmonary bypass for coronary artery operations does not influence postoperative cognitive function: a prospective, randomized trial. J Thorac Cardiovasc Surg1997; 114: 123—8.
23.
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. Anesthesiology2001; 95: 1110—9.
24.
Regragui I., Birdi I., Izzat MB et al. The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: a prospective randomized trial. J Thorac Cardiovasc Surg1996; 112: 1036—45.
25.
Mora CT, Henson MB, Weintraub WS et al. The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg1996; 112: 514—22.
26.
Nathan HJ, Wells GA, Munson JL et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: a randomized trial. Circulation2001; 104: 185—91.
27.
Nathan HJ, Lavallee G.The management of temperature during hypothermic cardiopulmonary bypass: I—Canadian survey. Can J Anaesth1995; 42: 669—71.
28.
Moody DM, Bell MA, Challa VR et al. Brain microemboli during cardiac surgery or aortography. Ann Neurol1990; 28: 477—86.
Moody DM, Brown WR, Challa VR et al. Brain microembloi associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg1995; 59: 1304—7.
31.
Brooker RF, Brown WR, Moody DM et al. Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary bypass. Ann Thorac Surg1998 ; 65: 1651—5.
32.
Solis RT, Noon GP, Beall AC et al. Particulate microembolism during cardiac operation. Ann Thorac Surg1974; 17: 332—44.
33.
Liu J-F., Su Z-K., Ding W-X.Quantitation of particulate microemboli during cardiopulmonary bypass: Experimental and clinical studies. Ann Thorac Surg1992 ; 54: 1196—202.
34.
Yao FS, Barbut D., Hager BA et al. Detection of aortic emboli by transesophageal echocardiography during coronary bypass surgery. Anesthesiology1995; 83: A126.
35.
Newman M., Croughwell N., Lowry E. et al. Age and cerebral emboli during cardiopulmonary bypass. Anesthesiology1995; 83: A131.
36.
Newman M., Croughwell N., Lowry E. et al. Emboli detection in warm and cold cardiopulmonary bypass. Anesthesiology1995; 83: A130.
37.
Brown WR, Moody DM, Challa VR et al. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke2000; 31: 707—13.
38.
Blauth C., Kohner EM, Arnold J. et al. Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography. Lancet1986; 2: 837—9.
39.
Stump DA, Kon NA, Rogers AT et al. Emboli and neuropsychological outcome following cardiopulmonary bypass. Echocardiography1996; 13: 555—8.
40.
Blauth CI, Arnold JV, Schulenberg WE et al. Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg1988; 95: 668—76.
41.
Clark RE, Brillman J., Davis DA et al. Microemboli during coronary artery bypass grafting. J Thorac Cardiovasc Surg1995; 109: 249—58.
42.
Harris Dnf, Bailey SM, Smith Plc et al. Brain swelling in first hour after coronary artery bypass surgery . Lancet1993; 342: 586—7.
Hunt BJ, Parratt RN, Segal HC et al. Activation of coagulation and fibrinolysis during cardiothoracic operations. Ann Thorac Surg1998; 65: 712—8.
45.
Boisclair MD , Lane DA, Philippou H. et al. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood1993; 82: 3350—7.
46.
Rubens FD, Labow RS, Lavallee GR et al. Hematologic evaluation of cardiopulmonary bypass circuits prepared with a novel block copolymer. Ann Thorac Surg1999; 67: 689—98.
47.
Tabuchi N., de Haan J., Boonstra PW et al. Activation of fibrinolysis in the pericardial cavity during cardiopulmonary bypass. J Thorac Cardiovasc Surg1993; 106: 828—33.
48.
Weitz JI, Hudoba M., Massel D. et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors . J Clin Invest1990; 86: 385—91.
49.
Chung JH, Gikakis N., Rao K. et al. Pericardial blood activates the extrinsic coagulation pathway during clinical cardiopulmonary bypass. Circulation1996; 93: 2014—8.
50.
Barstad RM, Ovrum E., Ringdal M-AL et al. Induction of monocyte tissue factor procoagulant activity during coronary artery bypass surgery is reduced with heparin-coated extracorporeal circuit. British Journal of Haematology1996 ; 94: 517—25.
51.
Ernofsson M. , Thelin S., Siegbahn A.Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study. J Thorac Cardiovasc Surg1997; 113: 576—84.
52.
Kitaguchi H. , Hijikata A., Hirata M.Effect of thrombin on plasminogen activator release from isolated perfused dog leg. Thromb Res1979; 16: 407—15.
53.
de Haan J., Boonstra PW, Monnink Shj et al. Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis. Ann Thorac Surg1995; 59: 901—7.
54.
de Haan J., Schonberger J., Haan J. et al. Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass. J Thorac Cardiovasc Surg1993; 106: 1017—23.
55.
de Haan J., Boonstra PW, Tabuchi N. et al. Retransfusion of thoracic wound blood during heart surgery obscures biocompatibility of the extracorporeal circuit. J Thorac Cardiovasc Surg1996; 111: 272—5.
56.
Ferraris VA , Ferraris SP, Singh A. et al. The platelet thrombin receptor and postoperative bleeding. Ann Thorac Surg1998 ; 65: 352—8.
Tracy PBRegulation of thrombin generation at cell surfaces. Semin Thromb Hemost1988; 14: 227—33.
59.
Kinlough-Rathbone RL, Perry DWProlonged expression of procoagulant activity of human platelets degranulated by thrombin. Thromb Haemostas1995; 74: 958—61.
60.
Edmunds LH, Saxena NC, Hillyer P. et al. Relationship between platelet count and cardiotomy suction return . Ann Thorac Surg1978; 25: 306—10.
61.
Carrier M., Denault A., Lavoie J. et al. Randomized controlled trial of pericardial blood processing with a cell-saving device on neurologic markers in elderly patients undergoing coronary artery bypass graft surgery. Ann Thorac Surg2006; 82: 51—5.
62.
Anderson RE, Hansson L-O., Liska J. et al. The effect of cardiotomy suction on the brain injury marker S100β after cardiopulmonary bypass. Ann Thorac Surg2000; 69: 847—50.
63.
Shann KG, Likosky DS, Murkin JM et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: a focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. J Thorac Cardiovasc Surg2006; 132: 283—90.
64.
Eagle KA, Guyton RA, Davidoff R. et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation2004; 110: e340—437.
65.
Taggart DP, Thomas B.Ferguson Lecture. Coronary artery bypass grafting is still the best treatment for multivessel and left main disease, but patients need to know. Ann Thorac Surg2006; 82: 1966—75.
66.
Sabik JF, Blackstone EH, Lytle BW et al. Equivalent midterm outcomes after off-pump and on-pump coronary surgery. J Thorac Cardiovasc Surg2004; 127: 142—8.
67.
Zamvar VY, Khan NU, Madhavan A. et al. Clinical outcomes in coronary artery bypass graft surgery: comparison of off-pump and on-pump techniques. Heart Surg Forum2002; 5: 109—13.
68.
Van Dijk D. , Jansen EW, Hijman R. et al. Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. JAMA2002; 287: 1405—12.
