1. University of Ulsan, Asan Medical Center Department of anesthesiology and pain management Professor In-Cheol Choi M.D., Ph.D.

2. Disclosure Neuroprotection

3. Neurologic Complication Stroke rate: 1-3% Cognitive dysfunction Attention, concentration, short-term memory Fine motor function 50-60%(postop) 25%(3 Mo) 15%(1yr) Newman MF, et.al. N Engl J Med 2001

5. Cause of Neurologic Injury Cerebral micro and macro emboli Global cerebral hypoperfusion Inflammation Hyperglycemia Cerebral hyperthermia Genetics Blood-brain barrier dysfunction

6. Types of Emboli Particulate macroemboli Atherosclerotic, calcific debris Gaseous microemboli Air Particulate microemboli Fat, marrow Cardiotomy suction

7. Gaseous Emboli 4 mm air bubble; 560 min 200 μm 100% O 2 ; 16 min Mechanism Occlusion of small arterioles, distal ischemia Activation of platelet, leukocyte, complements – Local injury, exacerbation of ischemic result TCD More sensitive to gaseous emboli

8. MICROEMBOLUS SIGNATURE ON POWER M-MODE AND SPECTRUM

10. Stroke rate 1 week after cardiac surgery as a function of atheroma severity. Atheroma was graded by transesophageal echocardiography as follows: Grade I, normal to mild intimal thickening; grade II, severe intimal thickening without protruding atheroma; Grade III, atheroma protruding less than 5 mm; Grade IV, atheroma protruding greater than or equal to 5 mm; Grade V, atheroma of any size with mobile components. Hartman et.al. Anesth Analg 1996; 83: 701-8. Atheroma grade Percentage of strokes (0/43) (0/80) (2/36) (2/19) (5/11)

13. Epiaortic Scanning (EAS) Ultrasound-guided assessment Palpation of aorta; insensitive for soft plaque Accurate image of aortic lumen Opimization of cann and X-clamp site

16. Transcranial Doppler cerebral emboli counts in patients in whom palpation versus epiaortic scanning (EAS) of the ascending aorta was used prior to aortic instrumentation, showing significantly fewer emboli with EAS. Murkin et.al. Heart Surg Forum 2003; 6:203. * p<0.05 cannulation* decannulation* on pump* partial clamp on* partial clamp off* X-clamp on X-clamp off total* Emboli

17. Incidence of modification of aortic cannula or aortic clamp application in a series of 102 patients in whom palpation of the ascending aorta was followed by epiaortic scanning (EAS) prior to aortic instrumentation, demonstrating that, in 23.5% of patients, EAS detected significant non-palpable atheroma, resulting in a change in management. Murkin et.al. Ann thorac Surg 2000; 70: 1791. (N = 102)

20. Cerebral Oximeter (INVOS ® )

21. 3-D view of cerebral vasculature illustrates monitoring of the vulnerable watershed region at the extremes of the circulation in the anterior and middle cerebral arteries.

22. Signal returns are received and analyzed to determine oxygen saturation of blood in the cerebral cortex beneath the sensors, delivering a reading of critical changes in brain blood oxygen levels. 730nm810nm

23. Murkin et.al. Heart Surg Forum 2004

24. Permanent Stroke and Pulmonary Complications were Reduced with Cerebral Oximetry Goldman et. al. Heart Surg Forum 2004

27. Incidence of awareness Sebel PS et.al. Anesth Analg 2004; 99: 833 - 9

29. Effects of Anaesthetics and Sedatives on the EEG burst suppression EEG Increasing Dose of Hypnotic Agent awake (  )deep (  ) near suppression

30. Awake Light/Moderate Sedation Deep Sedation General Anaesthesia Deep Hypnotic State Flat Line EEG 100 70 60 40 0 BIS BIS Range Guidelines Moderate Hypnotic State Light Hypnotic State

31. InductionInduction IncisionIncision MaintenanceMaintenance EmergenceEmergence 90 EEG Display SuppressionRatioSuppressionRatio Electromyograph Bar Signal Quality Index Bar Signal Quality Index Bar BIS Value

32. BIS Correlates with Brain Glucose Metabolic Rate Alkire Mike. Quantitative EEG Correlations with Brain Glucose Metabolic Rate during Anesthesia in Volunteers. Anesthesiology 1998; 89 (2):323-333. 34 95 62 66 Conditions which effect metabolic rate may effect BIS Anaesthesia Hypothermia Re-warming Ischaemia

33. NIRS BISSR

37. Pharmacologic Neuroprotection Thiopentone Remacemide Magnesium S(+)-ketamine Xenon Lidocaine β-blocker Aprotinin Corticosteriods Glypromate

38. Thiopentone Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Nussmeier et.al. Anesthesiology 1986; 64: 165-170. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Zaidan et.al. Anestheiology 1991; 74: 406-411.

39. Remacemide Noncompetitive NMDA-receptor antagonist Randomized trial of 171 CABG patients For 4 days prior to and 5 days after CABG 9 neuropsychological study 8 weeks after 9% vs 12% Reflection of learning ability (P<0.05) Arrowsmith et.al. Stroke 1998;29: 2357-62

40. Lidocaine Na + channel blockade, anti-inflammation 55 pts: valvular surgery 1 mg/min: induction-48hr Postop 8 day (p<0.05) Mitchell et.al. Ann Thorac Surg 1999; 67: 1117-24 Wang et. al. Anesth analg 2002. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Mathew et. al. Stroke 2009; 40: 880-7.

42. Aprotinin Levy et.al. Circulation 1995; 92: 2236-44. Frumento et.al. Ann Thorac Surg 2003. Anti-inflammatory action(?) Modulation of cerebral emboli(?) Mangano et.al. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354: 353-65. BART study

43. Corticosteriods Reduce inflammatory response CRASH trial Lancet 2004; 364: 1321-8. 10,008 pts Increase risk of death in high dose group Hyperglycemia Chaney et.al. Chest 2002; 121:921-31. Lazariods – steroid analogues

44. Glypromate N-terminal tripeptide of insulin-like growth factor-1 glycine-praline-glutamate Faborable results from Phase IIa Phase III clinical trial

49. 감사합니다 !