Brain Protection in Cardiac Surgery (eBook)

Brain Protection in Cardiac Surgery 2
Foreword 4
Preface 6
Series Preface 7
Contents 9
Contributors 11
1: Molecular and Biochemical Basis of Brain Injury Following Heart Surgery – Interventions for the Future 14
1.1 Introduction 14
1.2 Current Neuroprotective Strategies 14
1.3 Hypothermic Circulatory Arrest, a Model for Understanding Brain Injury in Cardiac Surgery 15
1.3.1 Clinical Aspects of HCA 15
1.3.2 Excitotoxicity in HCA 15
1.3.3 Our Laboratory Experience 17
1.4 New Directions in Identifying Molecular Mechanisms of Brain Injury and Cardiac Surgery 17
1.4.1 Genomics and Gene Microarrays 17
1.4.2 The Canine Genome 18
1.5 Valproic Acid – A Novel Neuroprotectant During HCA 18
1.6 Future Directions – Proteomics and the Development of Biomarkers for Brain Injury in Cardiac Surgery 19
1.6.1 Proteomics 19
1.6.2 The Need for Biochemical Markers to Monitor Brain Injury 20
1.6.3 a[Alpha]II-Spectrin Breakdown Products: A Novel Brain Injury Biomarker 20
1.6.4 Advantages of SBDP150 and SBDP120 over Other Current Markers 20
1.7 Early and Late Cognitive Dysfunction May Result from Different Etiologies 21
1.8 Clinical Relevance for Study of Molecular Mechanisms 21
References 22
2: Cardiopulmonary Bypass Circuit and the Brain 24
2.1 Oxygenators 25
2.2 Filters 25
2.3 Tubing and Coating 25
2.4 Pumps 26
2.5 Venous Reservoirs 26
2.6 Cardiotomy Suction/Cell Saver 26
2.7 Cannulas 27
2.8 Other Factors 27
2.9 Iatrogenic Contributions to Emboli 28
2.10 Conclusion 29
References 29
3: Neurological and Cognitive Sequelae of Cardiac Surgery 32
3.1 Introduction 32
3.2 Stroke 33
3.2.1 Mechanism of Stroke 33
3.2.2 Embolization 34
3.2.3 Hypoperfusion 34
3.2.4 Silent Infarcts 34
3.2.5 Defining the “High Risk” Patient 34
3.3 Postoperative Encephalopathy 35
3.4 Cognitive Outcomes 35
3.4.1 Short-Term Cognitive Changes 36
3.4.2 Mechanisms 36
3.4.3 Long-Term Cognitive Changes 37
3.4.4 Off-Pump CABG (OPCAB) 38
3.5 Future Directions 38
References 39
4: Neurocognitive Decline Following Cardiac Surgery: Incidence, Risk Factors, Prevention, and Outcomes 42
4.1 Preoperative Workup 42
4.2 Populations at Risk 43
4.3 Mechanisms of Injury 44
4.4 Strategies for Reducing Injury (Table 4.2) 45
4.5 Neuroprotective Strategies 46
4.6 Prognosis 46
References 47
5: Neuropathology of Brain Injury in Cardiac Surgery 50
5.1 Introduction 50
5.2 Basic Principles 50
5.3 Focal Ischemic Injury 51
5.3.1 Air Emboli 52
5.4 Global Ischemic Injury 52
5.5 Hypotensive Brain Injury 53
5.6 Pediatric Brain Injury 53
5.7 The Respirator Brain 55
5.8 Specific Pathologies Seen After Cardiac Surgery 55
5.8.1 Surgery for Congenital Heart Disease 55
5.8.2 Adult Cardiac Surgery 55
5.9 Summary 56
References 56
6: Biochemical Markers of Brain Injury 58
6.1 Introduction 58
6.2 Established Markers of Brain Injury Following Cardiac Surgery 59
6.3 Inflammatory Markers and Brain Injury 60
6.4 Investigational Markers of Brain Injury 63
6.5 Genetic Markers of Brain Injury 64
References 66
7: Pitfalls of Neuropsychometric Assessment and Alternative Investigative Approaches 69
7.1 Introduction 69
7.2 Assessment of Cerebral Injury 69
7.2.1 Neuropsychometric Assessment 69
7.2.2 Definition of Cognitive Decline 70
7.3 Limitations 71
7.3.1 Definition of Impairment 71
7.3.2 Baseline Performance and Regression to the Mean 71
7.3.3 Test Selection 72
7.3.4 Control Group 72
7.3.5 Attrition and Follow-Up 73
7.4 Summary 73
7.5 Alternative Investigative Approaches 73
7.6 Conclusions 75
References 75
8: Imaging of the Brain in Cardiac Surgery as a Tool in Brain Protection Studies 77
8.1 Methods for Assessing Brain Injury After Cardiac Surgery 77
8.2 MRI of the Brain in Cardiac Surgery 79
8.3 Clinical Significance of MRI Lesions 80
References 82
9: Current Techniques of Emboli Detection and Their Utility in Brain Protection Studies 85
9.1 Introduction 85
9.2 Techniques of Emboli Detection and Brain Injury 85
9.2.1 Retinal Fluorescein Angiography 86
9.2.2 Ultrasound 86
9.2.3 Echocardiography 87
9.2.4 Pathoradiology 87
9.3 Brain Imaging 87
9.3.1 Computerized Tomography 87
9.3.2 Magnetic Resonance Imaging 87
9.3.3 Single Photon Emission Computed Tomography 88
9.3.4 Fluid Attenuated Inversion Recovery 88
9.3.5 Diffusion-Weighted Imaging 88
9.3.6 Perfusion Imaging 88
9.3.7 Nuclear Magnetic Resonance Spectroscopy 88
9.4 Techniques and Studies to Reduce Embolization 89
9.4.1 Perfusion 89
9.4.2 Pharmacological 89
9.4.3 Surgical 90
9.5 Summary 90
References 91
10: Intraoperative Brain Monitoring in Cardiac Surgery 94
10.1 Introduction 94
10.2 Routine Clinical Monitoring 95
10.3 Jugular Venous Oximetry 96
10.3.1 Intraoperative SjO2 Monitoring 96
10.3.2 Neurological Outcome 97
10.4 Near Infrared Spectroscopy 98
10.4.1 Types of Cerebral Oximeter 99
10.4.2 Regional Cerebral Oxygen Saturation (rSO2) 99
10.5 Clinical Applications of NIRS 101
10.6 Transcranial Doppler Sonography 101
10.7 TCD in Cardiac Surgery 102
10.8 Embolus Detection 103
10.9 Electroencephalography 104
10.10 Pre- and Postoperative Monitoring 106
10.11 Intraoperative Monitoring 107
10.11.1 Carotid Artery Surgery 107
10.11.2 EEG Monitoring During Cardiac Surgery 108
10.11.3 Depth of Anesthesia Monitoring 109
10.12 Evoked Potential Monitoring 109
10.12.1 Somatosensory-Evoked Potential Monitoring 109
10.12.1.1 Clinical Applications 111
10.12.2 Auditory Evoked Potential Monitoring 111
10.12.2.1 Clinical Applications 113
10.13 Multimodal Brain Monitoring 113
10.14 Conclusions 115
References 115
11: Near-Infrared Spectroscopy Monitoring in Cardiac Surgery: Theory, Practice, and Utility1 123
11.1 Near-Infrared Spectroscopy 123
11.2 Beer–Lambert and the Measure of Tissue Oxygen Saturation 124
11.2.1 Multiwavelength NIRS and Absolute Versus Relative Oxygen Saturation 125
11.3 Temporal Resolution 125
11.3.1 Extracerebral Tissue 125
11.4 Spatial Resolution 126
11.5 Cerebral Arterial/Venous Blood Partitioning 126
11.6 NIRS Devices 127
11.7 NIRS Limitations and Confounds 127
11.7.1 NIRS Device Sensitivity 127
11.7.2 Melanin and Other Tissue Chromophores 128
11.7.3 Nonmetabolizing Tissue 128
11.8 Overview of NIRS Clinical Studies 128
11.9 NIRS in the Setting of Cerebral Ischemia 129
11.9.1 Carotid Endarterectomy 129
11.9.2 Retrograde and Selective Anterograde Cerebral Perfusion 131
11.10 Cerebral NIRS and Systemic Outcomes 131
11.11 Clinical Strategies for Low rSO2 132
11.11.1 Rule Out Mechanical Obstruction 133
11.11.1.1 Arterial Malperfusion 133
11.11.1.2 Superior Vena Cava Obstruction 133
11.11.2 Increase Mean Arterial Pressure 133
11.11.3 Verify Systemic Oxygenation 133
11.11.4 Normalize PaCO2 134
11.11.5 Optimize Hemoglobin 134
11.11.6 Evaluate Cardiac Function 134
11.11.7 Decrease CMRO2 135
11.11.8 Other Therapeutic Alternatives 135
11.12 Other Applications for NIRS 135
References 136
12: The Design and Methodology of Clinical Studies of Neuroprotection in Cardiac Surgery 140
12.1 Introduction 140
12.2 Neurocognitive Testing 141
12.2.1 Background 141
12.2.2 Group Mean Analysis 141
12.2.3 Incidence Analysis 142
12.2.4 Regression to the Mean 142
12.3 Biochemical Markers of Cerebral Injury 144
12.4 Neuroimaging 145
12.5 Conclusion 145
References 146
13: Temperature and Brain Protection in Cardiac Surgery 150
13.1 The Role of Temperature in Cerebral Physiology and Physiopathology 150
13.2 CNS Injury in the Cardiac Surgical Perioperative Period 151
13.2.1 Incidence and Risk Factors for the Development of Complications 151
13.2.2 Risk Stratification 151
13.2.3 Improving Risk Stratification 152
13.2.4 Minimizing the Risk of CNS Injury 152
13.3 Perioperative Temperature Management 152
13.3.1 Temperature Regimens 152
13.3.2 The Deleterious Effects of Hyperthermia 153
13.3.2.1 Background 153
13.3.2.2 Specific Effects of Hyperthermia Related to Cardiac Operations 153
13.3.3 The Benefits of Hypothermia 153
13.3.4 Sites for Temperature Monitoring 154
13.3.5 Methods of Achieving Hypothermia 154
13.3.6 Deep Hypothermic Circulatory Arrest 155
13.3.7 Total Body Hypothermia During Cardiopulmonary Resuscitation and Cardiovascular Collapse 157
13.3.8 Impact of Hypothermia on Other Organ Systems 157
13.3.8.1 Cardiovascular System 157
13.3.8.2 Respiratory System 157
13.3.8.3 Renal System 157
13.3.8.4 Gastrointestinal Function 157
13.3.8.5 Hematologic Function 158
13.3.9 Postoperative Hyperthermia and Induced Hypothermia 158
13.3.10 Treating Hyperthermia 159
13.4 Studies of Temperature and Neuroprotection 159
13.4.1 Clinical Studies Assessing the Effect of Temperature on Neurologic Outcome in Cardiac Surgery 159
13.4.2 Recommendations for Perioperative Temperature Management 162
References 162
14: Studies of Nonpharmacological Interventions to Reduce Brain Injury 167
14.1 Introduction 167
14.2 Definitions of Brain Injury Following Cardiac Surgery 167
14.3 Incidence of Brain Injury Following Cardiac Surgery 167
14.4 Factors Predisposing to Brain Injury Post Cardiac Surgery 169
14.5 Cerebral Physiology and Metabolism 169
14.5.1 Effects of Blood Gas and Temperature Management on Cerebral Vasculature 169
14.5.2 Cerebral Metabolism 170
14.6 Intraoperative Monitoring of Brain Injury During Cardiac Surgery 170
14.6.1 Noninvasive Methods 170
14.6.1.1 Transcranial Doppler 170
14.6.1.2 Echocardiography 170
14.6.1.3 Epiaortic Ultrasound Scanning 171
14.6.1.4 Electroencephalogram 171
14.6.1.5 Near-Infrared Spectroscopy 171
14.6.2 Invasive Methods 172
14.6.2.1 Jugular Venous Oxygen Saturation 172
14.7 Prevention of Brain Injury 172
14.7.1 Reduction of Embolic Load 172
14.7.1.1 Arterial Line Filters 172
14.7.1.2 Perfusion Intervention 173
14.7.1.3 Oxygenators 173
14.7.1.4 Aortic Manipulation 173
14.7.1.5 Off-Pump Coronary Artery Bypass Graft Surgery 174
14.7.1.6 Lipid Emboli 175
14.7.2 Temperature Management 175
14.7.3 Blood Gas Management 176
14.7.4 Deep Hypothermic Circulatory Arrest 177
14.7.5 Cerebral Perfusion 177
14.7.5.1 Retrograde Cerebral Perfusion 178
14.7.5.2 Selective Antegrade Cerebral Perfusion 178
14.8 Conclusions 179
References 179
15: Pharmacological Studies to Reduce Brain Injury in Cardiac Surgery 184
15.1 Introduction 184
15.2 Glutamate Receptor Blockers 184
15.3 Nitric Oxide Synthase Inhibitors 186
15.4 Barbiturates 186
15.5 Propofol 187
15.6 Volatile Anesthetics 187
15.7 Steroids 188
15.8 Free Radical Scavengers 189
15.9 Mannitol 189
15.10 Calcium Channel Blockers 189
15.11 Beta-Adrenergic Receptor Antagonists 190
15.12 Aprotinin 190
15.13 Anticonvulsants 190
15.14 Lidocaine 191
15.15 Calcineurin Inhibitors 191
15.16 GM1-Ganglioside 191
15.17 Fructose-1,6-Bisphosphate 191
15.18 Glucose Insulin Potassium Solutions 192
15.19 Diazoxide 192
15.20 Gene Therapy (Nuclear Factor-k(kappa)B Decoy) 192
15.21 Erythropoietin 193
15.22 Summary 193
References 193
16: Off-Pump and On-Pump Coronary Artery Surgery and the Brain 197
16.1 Introduction 197
16.2 Differences in Cerebral Pathophysiology Between Off- and On-Pump CABG Surgery 198
16.2.1 Cerebral Hypoperfusion 198
16.2.1.1 Dislocation of the Heart 198
16.2.1.2 Cerebral Hyperthermia 198
16.2.1.3 Hemodilution 199
16.2.1.4 Character of Blood Flow 199
16.2.1.5 Acid–Base Management 199
16.2.2 Cerebral Embolization 199
16.2.2.1 Macro-Emboli 200
16.2.2.2 Micro-Emboli 200
16.2.3 Summary of Differences in Cerebral Pathophysiology 200
16.3 Cerebral Outcomes: “T’ain’t What You Do (It’s the Way That You Do It)” 200
16.3.1 Methodology 201
16.3.2 Stroke 201
16.3.3 Cognition 204
16.3.3.1 Dichotomized Cognitive Outcomes 205
16.3.3.2 Continuous Cognitive Outcomes 205
16.3.3.3 Randomized Controlled Trials 206
16.3.3.4 Cognition More than 2 Years Postoperatively 207
16.3.3.5 Physiological Differences and Cognitive Outcome 207
16.3.3.6 CPB is Not a Cause of Cognitive Decrements 207
16.4 Conclusions 208
References 208
17: Experimental Basis and Clinical Studies of Brain Protection in Pediatric Heart Surgery 212
17.1 Background: Improving Outcomes in Pediatric Cardiac Surgery 212
17.2 Improvements in Cardiopulmonary Bypass 212
17.2.1 Hardware 212
17.2.2 Hypothermia 212
17.2.3 Cardiopulmonary Bypass Prime 213
17.2.4 Gas Strategy 213
17.2.5 Additives 213
17.3 pH Strategy and Hypothermic Bypass 213
17.3.1 pH Stat Strategy 213
17.3.2 Alpha Stat Strategy 214
17.3.3 An Epidemic of Choreoathetosis 214
17.3.4 Laboratory Study of pH Strategy 214
17.3.5 Randomized Prospective Trial of pH Strategy 214
17.4 Hemodilution and Cardiopulmonary Bypass 215
17.4.1 Laboratory Study of Hemodilution 215
17.4.2 Retrospective Clinical Study of ASD Closure 215
17.4.3 Randomized Clinical Trial of Hematocrit 215
17.5 Interaction of Bypass Conditions to Determine Outcome after Circulatory Arrest or Low Flow Bypass 216
17.5.1 Deep Hypothermic Circulatory Arrest 216
17.5.2 Low Flow Bypass 217
17.6 The Role of Serpins in Reducing Brain Injury During Cardiac Surgery 218
17.6.1 Background 218
17.6.2 Possible Mechanisms of Neuroprotection Afforded by Aprotinin 218
17.6.2.1 Vascular and Anti-inflammatory 218
17.6.2.2 Inhibition of NMDA Excitotoxicity by Aprotinin 218
17.6.2.3 Aprotinin and Excitotoxic Neuronal Injury in a Cell Culture Model 219
17.6.2.4 Laboratory Studies of Aprotinin in a Survival Porcine Model 219
Intravital Microscopy Study 219
Near-Infrared Spectroscopy 219
17.7 Conclusions 221
References 221
18: Experimental Basis and Clinical Studies of Brain Protection in Aortic Arch Surgery 223
18.1 Introduction 223
18.2 Hypothermic Circulatory Arrest 223
18.3 Selective Antegrade Perfusion 226
18.4 Retrograde Perfusion 228
18.5 Axillary Artery Cannulation 229
18.6 Trifurcated Graft Technique 230
18.7 Summary 231
References 231
19: The Future of Brain Protection in Cardiac Surgery 233
19.1 Introduction 233
19.2 Mechanisms of Brain Injury in Cardiac Surgery 233
19.3 Preoperative and Preventive Strategies 233
19.3.1 Clinical Risk Prediction 234
19.3.2 Genetic Identification 234
19.3.3 Biochemical Markers 235
19.3.4 Pharmacological Preventive Strategies 235
19.4 Intraoperative Strategies 235
19.4.1 Minimizing Emboli Generation 236
19.4.2 Brain Monitoring 236
19.4.3 Temperature Control 236
19.5 Postoperative Interventions 237
19.5.1 Strategies for Blood Conservation 237
19.5.2 N-Methyl-D-Aspartate (NMDA) Blocker 237
19.5.3 Magnesium 238
19.5.4 Deferoxamine 238
19.5.5 Complement Inhibitors 238
References 239
Index 242