Intensive Care Medicine (eBook)

Table of contens 5
List of Contributors 11
Common Abbreviations 28
I Genomics and Proteomics 29
Rethinking Sepsis: New Insights from Gene Expression Profiling Studies 30
Introduction 30
How to Identify and Measure Heterogeneity 30
Sources of Heterogeneity in Sepsis Patients 31
New Insights from Gene-expression Studies 32
Limitation of Current Risk Stratification Methods 33
Host Response in Sepsis is More Complex Than Previously Thought 33
There Is Strong Evidence of Heterogeneity at the Genomic Level 33
Genomic Heterogeneity 34
What Gives Rise To Genomic Heterogeneity? 34
Main Sources of Genomic Variability 35
Further Questions on an Existing Sepsis Model 36
Functional Mapping of Sepsis Genome to Monitor Immune Function 37
Conclusion 39
References 39
Mitochondrial Genetics and Sepsis 41
Introduction 41
Oxidative Phosphorylation and ATP Generation 41
Reactive Oxygen Species 42
Apoptosis 42
Mitochondria and Sepsis 43
Mitochondrial Genetics 43
Mitochondrial Haplogroups 44
Haplogroups and Human Disease 45
Haplogroups and Mitochondrial Function 46
Mitochondrial Biogenesis 46
Conclusion 47
References 47
Lung Proteomics in Intensive Care 50
Introduction 50
The Search for Biomarkers 50
What is a Biomarker? 50
The Need for Proteomics in the Intensive Care Unit 51
Genomics versus Proteomics 51
Lung Proteomics 52
Basics 52
What Intensivists Should Know About Proteomic Methods 52
Caveats 56
Applications in ALI/ARDS 58
In vitro 58
In vivo Animal Models 58
Clinical Studies 58
Future Directions 59
Epithelial Lining Fluid 59
Exhaled Breath Condensates 60
Decreasing the Noise to Discover the Signal 60
Conclusion 61
References 62
II Inflammatory Response 64
The Host Response to Sepsis 65
Introduction 65
Epidemiology and Genetic Variability 66
Pathogen Recognition Systems 67
Coagulation and Anticoagulation 70
Immune Suppression and Apoptosis 72
HMGB1 and RAGE 72
The Cholinergic Anti-inflammatory Pathway 73
Macrophage Migration Inhibitory Factor 74
C5a and C5a Receptor 74
Conclusion 74
References 74
Endotoxin Tolerance: Mechanisms and Clinical Applicability 77
Introduction 77
Mechanisms of Endotoxin Tolerance 77
Toll-like Receptors 77
Anti-inflammatory Hypothesis and Leukocyte Reprogramming 78
Endothelial Function and Microcirculation during LPS Tolerance 79
Clinical Applicability and Therapeutic Possibilities 81
Cross-tolerance 81
Conclusions 82
References 82
Oxidative Stress and Endothelial Dysfunctionduring Sepsis 85
Introduction 85
Sources and Actions of ROS and RNS in the Endothelium during Sepsis 85
Mechanisms of Endothelial Dysfunction during Sepsis 87
Conclusion 89
References 90
Measurement of Carbon Monoxide: From Benchto Bedside 91
Introduction 91
Carbon Monoxide Measurement 91
Carbon Monoxide Concentrations in Critically Ill Patients 92
Carbon Monoxide Concentrations and Lung Diseases 96
Carbon Monoxide Concentrations and Other Diseases 103
Conclusion 103
References 103
Monitoring Immune Dysfunction in Septic Patients: Toward Tailored Immunotherapy 107
Introduction 107
Monocyte Dysfunction 108
Functional Testing 108
Cell Surface Marker Expression 109
Mechanisms Responsible for Monocyte Dysfunction 109
Restoration of Monocyte Functions 110
T Lymphocyte Dysfunction 111
Functional Testing 111
Cell Surface Marker Expression 112
Mechanism Responsible for Lymphocyte Dysfunction 112
Restoration of Lymphocyte Functions 113
Conclusion 114
References 115
III Current and Future Management of Sepsis 117
Source Control in the ICU 118
Introduction 118
What is ‘Source Control’? 118
Elements of Source Control 119
Drainage 119
Decompression 120
Debridement 120
Restoration of Anatomy and Function 120
Do we need to perform Source Control? 120
When to Perform Source Control? 121
The Role of the Intensivist 121
What if Source Control is Impossible or Fails? 123
Special Considerations in Critically Ill Patients 123
Timing of Source Control 123
Definitive Therapy or Temporary Measures 124
How to Recognize Failed Source Control? 124
Conclusion 125
References 125
IgM-enriched Immunoglobulins in Sepsis 127
Introduction 127
Mechanisms of Action of IVIG in Sepsis 128
Differences between IgG- and IgM-enriched Immunoglobulins 129
Clinical Significance of IgM-enriched IVIG 130
Conclusion 133
References 134
Clarithromycin: A Promising Immunomodulatorin Sepsis 136
Introduction 136
Indirect Evidence for an Immunomodulatory effect of Macrolides in Pneumonia 137
Lessons from Animal Studies 138
Clinical Efficacy of Clarithromycin as an Immunomodulator in Sepsis 139
Conclusion 141
References 142
High-flow Hemofiltration as an Adjunctive Therapy in Sepsis 144
Introduction 144
Mechanism of Action: Hemofiltration as a New Shield against the ‘Chaos Theory’ and ‘Complex Non-linear Systems’ in Sepsis 144
Recent Animal Trials and Clinical studies Highlighting the Crucial Roles of Dosing and Timing 146
Practical Aspects for the Bedside Clinician 148
Future Directions Regarding the Use of Hemofiltration in Sepsis 149
Conclusion 150
References 151
Economic and Social Burden of Severe SepsisE. Silva 154
Introduction 154
Concepts 154
Direct Costs of Sepsis Management 156
Direct Costs of Sepsis Management in Developing Countries: A Brazilian Experience 157
Indirect Costs and Burden of Illness 158
Impact of Therapeutic Strategies on Costs 159
Conclusion 161
References 162
IV Proposed Targets for New Therapies 164
Lymphocyte Apoptosis in Sepsis and Potential Anti-apoptotic Strategies 165
Introduction 165
Mechanisms of Apoptosis 166
Pathways Involved in Apoptosis 166
Evidence in Animals 168
Caspase-cascade 169
Fas/CD95-induced apoptosis 169
Mitochondrial Pathway 170
Evidence in Humans 170
Therapeutic Molecular Targets 171
Conclusion and Perspectives 172
References 172
The Pivotal Role of Beta-adrenoreceptors in Critical Illness Pathophysiology 175
Introduction 175
New Concepts in Adrenoreceptor Signaling Biology 175
Desensitization of Beta-adrenoreceptors 177
Catecholamine-induced Immune Dysregulation 178
Beta-adrenoreceptor-mediated Metabolic Effects of Critical Illness 180
Beta-adrenoreceptor-mediated Effects on Barrier Gut Function 181
Specific Beta-adrenoreceptor-mediated Roles in Common Critical IllnessPathophysiology 181
Traumatic Head Injury 181
Cardiovascular Dysfunction during Critical Illness 181
Acute Lung injury 182
Limitations of Current Experimental/clinical Data 182
Conclusion 182
References 183
Non-septic Acute Lung Injury and Inflammation: Role of TLR4 186
Introduction 186
Participation of TLR4 in Ischemia-reperfusion Injury 186
Heme Activates TLR4 by Different Mechanisms than does LPS 187
Acute Lung Injury Produced by Avian Influenza Virus H5N1 or Acid Aspiration is Dependent on Activation of TLR4 By Oxidized Phospholipids 189
Fragmented Hyaluronic Acid activates TLR4 189
TLR4 Participates in Late Inflammatory Responses in which HMGB1 Plays a Contributory Role 190
Heat Shock Proteins (HSP) Induce Pro-inflammatory Cytokine Release through TLR4 190
TLR4 Participates in Ethanol-induced Inflammation 191
Acetaminophen-induced Liver Injury is TLR4-dependent 191
Conclusion 192
References 192
Hydrogen Sulfide: A Metabolic Modulator and a Protective Agent in Animal Models of Reperfusion Injury 195
Introduction 195
The Biological Chemistry of Hydrogen Sulfide 195
H2S as an Inducer of a State Resembling Suspended Animation 196
Protective Effects of H2S in Local or Whole-body Ischemia or Ischemia-reperfusion 198
Conclusion 200
References 200
V Septic Shock 204
‘Myocardial Depression’ or ‘Septic Cardiomyopathy’? 205
Introduction 205
Septic Cardiomyopathy: A Secondary Cardiomyopathy in the Scope of the Systemic Disease, ‘Sepsis’ 205
How to Quantify Septic Cardiomyopathy? 208
Septic Cardiomyopathy is of Prognostic Relevance 209
Septic Cardiomyopathy: Triggers and Mechanisms 210
Pump Failure 210
The Role of Arrhythmias in Septic Cardiomyopathy 211
The Heart as a ‘Cytokine Producer’ 211
Impaired Regulation of Cardiac Function in Septic Cardiomyopathy 212
Possible Mechanisms of Impaired Regulation of Cardiac Function in Sepsis: Pacemaker HCN Channels as Targets 212
Causal Approaches towards the Treatment of Acute Septic Cardiomyopathy 213
Conclusion 214
References 214
Determinants of Tissue PCO2 in Shock and Sepsis: Relationship to the Microcirculation 217
Introduction 217
Mechanisms of Increase in Venous and Tissue PCO2: The Basics 217
Intramucosal Acidosis in Sepsis 223
Conclusion 224
References 225
Refining the Tools for Early Goal-directed Therapy in Septic Shock 227
Introduction: Initial Management of Septic Shock 227
Overview of Early Goal-directed Therapy 227
Therapeutic Steps and Goals and Proposed Refinements 230
Fluid Titration to Predictors of Fluid Responsiveness 230
Fluid Titration to Mean Arterial Pressure 231
Vasopressor Titration to MAP 232
The Goal: Tissue Perfusion 234
Red Blood Cell Transfusion 235
Inotrope Therapy 235
Other Issues 236
Early Recognition of Severe Sepsis 236
Early Antimicrobials 236
Vasopressor Weaning 236
Conclusion 237
References 238
VI Intravenous Fluids 241
Hyperchloremic Metabolic Acidosis: More than Just a Simple Dilutional Effect 242
Introduction 242
Mechanisms Underpinning pH Regulation: A Physico-chemical Approach 242
Effects of Plasma Volume Expansion on pH 244
Clinical Consequences of Hyperchloremic Metabolic Acidosis 245
Fluid Resuscitation and Electrolyte Manipulation 245
Pulmonary Compensation/Acute Lung Injury 246
Coagulation Cascade 247
Microvascular Flow 248
Immune Activation or Suppression 249
Survival 250
Conclusion 251
References 251
Old versus New Starches: What do We Know about their Differences? 254
Introduction 254
Hydroxyethyl Starch Pharmacokinetics 254
Volume Effects 255
Renal Effects 257
Coagulation and Bleeding 257
Tissue Storage 259
Pruritus 259
Long-term Survival 260
Conclusion 260
References 261
Impact of Hydroxyethyl Starch on Renal Function 264
Introduction 264
Pharmacokinetic Profile of HES Solutions 264
Pathomechanisms of HES-induced Renal Dysfunction 266
Clinical Evidence of HES-induced Renal Dysfunction 268
Conclusion 271
References 272
Rational Approach to Fluid Therapy in Acute Diabetic Ketoacidosis 275
Introduction 275
Historical Perspective 275
Pathophysiology 276
Aims of Fluid Therapy 277
Optimal Management 278
Evidence Base for 0.9 % Saline 278
Problems with 0.9 % Saline 278
Evidence Base for 0.45 % Saline 279
Evidence Base for Hartmann’s Solution 280
Evidence Base for Colloids 281
Conclusion 282
References 282
VII Hemodynamic Support 284
Cardiac Filling Volumes and Pressures in Assessing Preload Responsiveness during Fluid Challenges 285
Introduction 285
Goals and Effects of Fluid Loading: Defining Preload and Fluid Responsiveness 285
Filling Pressures and Volumes of the Heart 286
Physiological Considerations and Clinical Implications 288
Conclusion 291
References 292
Update on Preload Indexes: More Volume than Pressure 295
Introduction 295
Filling Pressures (CVP and PAOP) 295
Continuous Right Ventricular End-diastolic Volume (cRVEDV) 297
Global-end Diastolic Volume and Intrathoracic Blood Volume 299
Conclusion 302
References 302
Monitoring Arterial Blood Pressure and Cardiac Output using Central or Peripheral Arterial Pressure Waveforms 305
Introduction 305
Wave Contour in the Central and Peripheral Arteries 306
Agreement between Central and Peripheral Blood Pressure in Specific Clinical Situations 308
Influence of the Site of Blood Pressure Measurement on Continuous Cardiac Output Estimation 309
Conclusion 314
References 314
Intrathoracic Pressure Regulation for the Treatment of Hypotension 317
Introduction 317
Active Intrathoracic Pressure Regulation Therapy for Apneic Hypotension Patients 317
Intrathoracic Pressure Regulation Therapy in Cardiac Arrest with CPR 318
Intrathoracic Pressure Regulation Therapy and CPR 319
Intrathoracic Pressure Regulation Therapy and Survival Outcomes in Hemorrhagic Shock 320
Intrathoracic Pressure Regulation Therapy and Sepsis 322
Potential Adverse Consequences and Limitations of Intrathoracic Pressure Regulation Therapy 323
Conclusion 323
References 324
Functional Hemodynamic Monitoring: A Personal Perspective 326
Introduction 326
Use of Dynamic Responses to Identify Nascent Cardiovascular States 327
Preload Responsiveness 327
Cardiovascular Sufficiency 328
Future Trends 329
References 330
VIII Airway Management 331
Endotracheal Intubation in the ICU 332
Introduction 332
Care Management Bundle to Increase the Safety of EndotrachealIntubation in the ICU 332
Pre-intubation Period 332
Per-intubation Period 334
Post-intubation Period 336
Conclusion 338
References 339
Pediatric Advanced Airway Management Training for Non-anesthesia Residents 341
Introduction 341
Risks associated with Tracheal Intubation and Provider Competence 341
Non-neonatal Intubation 341
Neonatal Intubation 343
Demand for Pediatric Airway Management Competence in Pediatric Resident Trainees 344
Process of Acquisition and Retention of Pediatric Tracheal Intubation Competence 345
Acquisition of Intubation Skill Competence 345
Retention of Intubation Skill Competence 346
Validation of and Evidence for Simulation in Tracheal Intubation Training 347
Future Directions 348
Conclusion 348
References 349
Automatic Tube Compensation in the Weaning Process 351
Introduction 351
Automatic Tube Compensation 352
Commercially available Automatic Tube Compensation Systems 352
Potential Clinical Uses of Automatic Tube Compensation 353
Increasing the Predictive Potential of a Spontaneous Breathing Trial 353
Studies using commercially available ATC systems 353
Potential Disadvantage of Reducing Imposed Workload 355
Use of Automatic Tube Compensation as a Weaning Predictor 355
Practical Aspects of using Automatic Tube Compensation 356
Conclusion 356
References 356
IX Mechanical Ventilation 358
Extracorporeal Membrane Oxygenation for Cardiac and Pulmonary Indications: Improving Patient Safety 359
Introduction 359
Application of ECMO Today 360
Indications for ECMO 360
Components of ECMO Devices 360
Further Development of ECMO 361
Oxygenator 361
Blood Pump 361
Modifications of ECMO Console and Circuit 362
Pumpless Extracorporeal Lung Assist 362
Control and Safety 363
Automation for Related Applications 363
Available Control and Safety Concepts for ECMO 364
New Control and Safety Concepts 364
Conclusion 365
References 366
Patient-ventilator Interaction during Non-invasive Ventilation 368
Introduction 368
NIV in Acute Respiratory Failure 368
Triggering of the Ventilator 369
Pressurization Slope 371
Level of Pressure Support 371
Cycling 372
Masks 373
Conclusion 374
References 374
Variable Mechanical Ventilation: Breaking the Monotony 377
Introduction 377
Patterns of Variability and their Characterization 377
Rationale for the Use of Variable Patterns in Mechanical Ventilation 379
History of Variable Mechanical Ventilation 379
Variable Controlled Mechanical Ventilation 380
Variable Assisted Mechanical Ventilation 381
Why does Respiratory Function Improve during Variable Mechanical Ventilation? 382
Is Variable Mechanical Ventilation Equivalent to Regular Ventilation with Intermittent Sighs? 384
Can Variable Mechanical Ventilation be Injurious? 385
Limitations of Variable Mechanical Ventilation 386
Conclusion 386
References 387
Life-threatening Asthma: Focus on Lung Protection 390
Introduction 390
Epidemiology 390
Definitions 391
Risk Factors 391
Pathophysiology of the Acute Asthma Attack 391
Therapeutic Approach 393
Pharmacological Therapy 393
Non-Invasive Ventilation 394
Intubation 395
Mechanical Ventilation 395
Assessing Lung Inflation 397
Analgesia, Sedation, Paralysis, and Inhaled Anesthetics 397
Heliox 398
Rescue Therapies 398
Conclusion 398
References 399
X Respiratory Monitoring 401
Bedside Monitoring of Diaphragm Electrical Activity during Mechanical Ventilation 402
Introduction and Background 402
Bedside Monitoring of EAdi 404
Conclusion 407
References 408
Electrical Impedance Tomography 411
Introduction 411
How Electrical Impedance Tomography Works 411
Reconstruction Algorithms 412
Patterns of Applying the Electrical Current 413
Absolute versus Difference Images 414
Spatial and Temporal Resolution 414
Clinical Applications 415
Assessment of Lung Recruitment and Lung Collapse 415
Detection of Pneumothorax and Pleural Effusion 418
Correct Placement of Endotracheal Tube 419
Potential Future Applications of Clinical Relevance 419
Conclusion 419
References 420
Regional Ventilation Delay Index: Detection of Tidal Recruitment using Electrical Impedance Tomography 422
Introduction 422
Individual PEEP Setting is Essential 422
Global and Regional Lung Function Parameters 423
Elecrical Impedance Tomography 423
The Concept of the Regional Ventilation Delay Index 424
Implementing Regional Ventilation Delay Index in Clinical Practice 425
Conclusion 428
References 428
Different Approaches to the Analysis of Volumetric Capnography 430
Introduction 430
Capnography: Types and Applications 430
Invasive Volumetric Capnography Variables 431
Non-invasive Volumetric Capnography Variables 432
Techniques for Volumetric Capnography Analysis 433
A New Algorithm for Volumetric Capnography Analysis 435
Conclusion 438
References 439
Variation in Extravascular Lung Water in ALI/ARDS Patients using Open Lung Strategy 441
Introduction 441
Measurement of EVLW at the Bedside 441
EVLW in ALI/ARDS Patients 444
Ventilation Strategy in ALI/ARDS and EVLW Variations 444
Conclusion 447
References 447
Clinical Utility of Extravascular Lung Water Measurements 450
Introduction 450
Measurement of EVLW 450
Gravimetry 451
Transpulmonary Dilution Techniques 451
Double indicator dilution technique 451
Single indicator dilution technique 452
Limitations of the Measurement of EVLW by Transpulmonary Dilution Techniques 452
Underestimation of EVLW during ARDS 452
Effects of Positive End-expiratory Pressure (PEEP) 454
Other limitations 454
Clinical Utility of EVLW 455
Diagnosis of Pulmonary Edema 455
Identification of the Mechanism of Pulmonary Edema 455
Prognostic Evaluation of Patients with ALI/ARDS 456
Guidance of Fluid Therapy in ARDS 456
EVLW for Guiding Ventilatory Strategy 457
Conclusion 457
References 457
Rationalizing the Use of Surgical Critical Care: The Role of Cardiopulmonary Exercise Testing 461
Introduction 461
Why Use Cardiopulmonary Exercise Testing as an Assessment Tool? 462
Which Patients should Undergo Cardiopulmonary Exercise Testing? 463
Cardiopulmonary Exercise Testing in Practice 464
1. Preparation 464
2. Data collection 465
3. Unloaded Cycling 465
4. Ramping Phase 465
5. Recovery Phase 466
Interpretation of Cardiopulmonary Exercise Test Data 466
1. The Anaerobic Threshold 466
2. Ischemic Heart Disease 467
a) The oxygen pulse response (VO2/heart rate) 467
b) Relationship of VO2 to work rate 467
c) Ventilatory Equivalent for CO2 (VE/VCO2) 468
Risk Stratification and Management using Cardiopulmonary Exercise Testing 468
Case Reports 469
Conclusion 475
References 475
Advanced Minimally Invasive Hemodynamic Monitoring of the High-risk Major Surgery Patient 477
Introduction 477
Definition and Role of Perioperative Optimization 477
Preoperative Period 477
Intraoperative Period 478
Postoperative Period 479
Overview of Some Current Advanced Hemodynamic Monitors 479
Non- or Minimally-invasive Measurement of Cardiac Output 479
Comparison of cardiac outputs from monitors used contemporaneously in the operating room 482
Use of the LiDCOplus and LiDCOrapid in the management of intraoperative hypotension 484
Decline in Use of Central Venous Catheterization for Major Surgery 486
Conclusion 486
References 486
Post-pneumonectomy Pulmonary Edema 489
Introduction 489
Diagnostic Criteria 489
Prevalence 489
Pathology 490
Etiology 490
Inflammation 491
1. Eicosanoids 491
2. Vascular endothelial growth factor (VEGF) 491
3. Tumor necrosis factor (TNF)- and the interleukins (IL) 492
Fluid Therapy and Reduction in Volume of the Pulmonary Vascular Bed 492
Disrupted Lymphatic Drainage 493
Oxidative Damage and Ischemia-Reperfusion Injury 493
Ventilation 494
Comorbidities 494
Chest Drains 494
Transfusion of Blood Products 495
Conclusion 495
References 496
The Role of Phenylephrine in Perioperative Medicine 499
Introduction 499
Pharmacological Characteristics of Phenylephrine 499
Contraindications for the Use of Phenylephrine 501
Use of Phenylephrine to Treat Perioperative Arterial Hypotension 501
General and Regional Anesthesia 501
Cardiac Surgery 502
Non-cardiac Vascular Surgery 503
Cesarean Section 503
Use of Phenylephrine in Postoperative Intensive Care Medicine 506
Vasodilatory Shock after Cardiac Surgery and Cardiopulmonary Bypass 506
Use of Phenylephrine in Sepsis-related Arterial Hypotension 507
Use of Phenylephrine in Cardiopulmonary Resuscitation 509
Summary and Conclusion 509
References 510
Role of the Calcium Sensitizer, Levosimendan, in Perioperative Intensive Care Medicine 514
Introduction 514
Mode of Action 515
Dosage and Pharmacokinetics 517
Clinically Relevant Side Effects 517
Metabolism 517
Severe Sepsis and Septic Shock 518
Perioperative Administration 519
Right Ventricular Dysfunction 520
Cardiogenic Shock 521
Cardiopulmonary Resuscitation 522
Conclusion 522
References 523
Inhaled Nitric Oxide Therapy in Adult Cardiac Surgery 527
Introduction 527
Generation and Metabolism 527
Local Cardiopulmonary Effects 528
Non-cardiovascular Effects 528
Pulmonary Hypertension and Right Ventricular Failure after CardiacSurgery 529
Pulmonary Hypertension 529
Right Ventricular Failure 529
Diagnosis 529
Administration of Nitric Oxide 530
Cardiac Surgery 531
Valve Operations 531
Adult Congenital Heart Disease 531
Ventricular Assist Device 532
Heart Transplantation 532
Lung Transplantation 532
Trial Data Relating to Outcome 532
Conclusion 532
References 533
XII Cardiac Function 536
Use of Natriuretic Peptides in the EmergencyDepartment and the ICU 537
Introduction 537
Natriuretic Peptides are Quantitative Markers of Cardiac Stressand Heart Failure 537
Clinical Indications: Patients with Acute Dyspnea 538
Diagnostic Value of Natriuretic Peptides in Patients with Acute Dyspnea 538
Prognostic Value of Natriuretic Peptides in Patients with Acute Dyspnea 539
Impact of Natriuretic Peptide on the Management of Patients with Acute Dyspnea 539
Added Value of Using Natriuretic Peptide in the Management of Patients with Acute Dyspnea 539
ICU Perspective 540
Conclusion 541
References 542
Abnormalities of the ST Segment 545
Introduction 545
Electrocardiographic Evaluation 545
Electrocardiographic Differential Diagnosis – ST Segment Abnormalities 551
Acute Coronary Syndrome 551
Benign Early Repolarization 553
Acute Myopericarditis 554
Left Ventricular Aneurysm 554
Other Patterns with ST Segment Abnormality 555
References 555
Functional Mitral Regurgitation in the Critically Ill 557
Introduction 557
Definition 558
Pathophysiology 560
Diagnosis 561
Therapeutic Management 563
Medical 563
Surgical 563
Conclusion 563
References 564
XIII Cardiopulmonary Resuscitation 566
Feedback to Improve the Quality of CPR 567
Introduction 567
The Importance of Quality CPR 567
Chest Compressions 567
Interruptions in Chest Compressions 568
Ventilation Rate and Hyperventilation 569
The Quality of CPR is often Sub-optimal during Clinical Resuscitation Attempts 570
Strategies for Improving the Quality of CPR 570
Real-time Feedback during CPR Training and Actual Resuscitation 570
Post-event Debriefing 572
Future Developments in Technology 573
Conclusion 574
References 574
The Post-cardiac Arrest Syndrome 577
Introduction 577
Phases of the Post-cardiac Arrest Syndrome 577
Pathophysiology of Post-cardiac Arrest Syndrome 578
Post-cardiac Arrest Brain Injury 578
Post-cardiac Arrest Myocardial Dysfunction 579
Systemic Ischemia/reperfusion Response 579
Persistent Precipitating Pathology 579
Treatment of the Post-cardiac Arrest Syndrome 579
Airway and Ventilation 580
Circulation 580
Disability (optimizing neurological recovery) 581
Post-cardiac Arrest Prognostication 583
Organ Donation 583
Conclusion 584
References 584
Use of a Standardized Treatment Protocol for Post-cardiac Resuscitation Care 587
Introduction 587
Chain of Survival 587
The Post-resuscitation Syndrome 589
Early Coronary Intervention 590
Induced Mild Hypothermia 590
Cerebral Blood Flow and Mean Arterial Blood Pressure 592
Hemodynamic Support and Monitoring 592
Ventilation 593
Blood Glucose and Electrolyte Monitoring 593
Thrombolytic Therapy Aimed at Improving Brain Perfusion 594
Brain Monitoring 594
Prevention of Infection 594
Use of Sedation, Analgesia and Paralyzing Agents 595
Slow, Passive or Active Re-warming and the Prevention of Fever 595
Prognostication 596
Future Perspectives 596
Conclusion 597
References 598
Therapeutic Hypothermia after Cardiac Arrest 601
Introduction 601
Effects of Hypothermia on Neurological Function Following Cardiac Arrest 602
Effects of Hypothermia on Myocardial Function after Cardiac Arrest 603
Timing and Methods for Inducing Hypothermia 604
Preliminary Experience with Selective Brain Cooling: Effects on Neurological and Myocardial Functions 606
Conclusion 609
References 609
XIV Renal Function 612
Biomarkers of Acute Kidney Injury in Critical Illness 613
Introduction 613
Conventionally used Indices of Renal Injury 614
Biomarkers of Renal Injury 614
Serum Markers 615
Urine Markers of AKI 616
Data on Biomarkers of AKI in Critical Illness 616
Biomarkers on the Horizon 619
What should an Intensivist do When Faced with an Abnormal Biomarker Result? 619
Conclusion 619
References 620
The Role of Biomarkers in Cardiac Surgery- associated Acute Kidney Injury 622
Introduction 622
What are the Characteristics of an Ideal Biomarker of Cardiac Surgery-associated-AKI? 622
Diagnostic Performance: How Good is a Test? 623
What Biomarkers are Needed? 624
What Biomarkers are Currently Available and How Good are They? 624
What Biomarkers are Under Development? 625
Neutrophil Gelatinase-associated Lipocalin 625
Interleukin-18 626
Kidney Injury Molecule-1 626
Cystatin C 626
Limitations of New Biomarkers 626
How will New Biomarkers Change the Diagnosis and Treatment of AKI? 627
Conclusion 627
References 628
Neutrophil Gelatinase-associated Lipocalin: An Emerging Biomarker for Angina Renalis 630
Introduction 630
Discovery of NGAL as an AKI Biomarker 630
NGAL for the Early Diagnosis of AKI 630
NGAL for Monitoring the Response to AKI Therapy 632
NGAL for the Prediction of AKI Outcomes 633
Limitations of NGAL as an AKI Biomarker 633
Conclusion 634
References 634
XV Hepatosplanchnic Function 637
ICG Clearance Monitoring in ICU Patients 655
Introduction 655
Physiology of Indocyanine Green 655
Principles of Measurement 656
Invasive Methods 656
Non-Invasive Methods 656
Limits of ICG Pharmacokinetics Interpretation 657
The Current Place of ICG in Clinical Practice (Table 2) 657
Prognostic Marker in the Intensive Care Unit 657
Hepatosplanchnic Hemodynamics In Different Clinical Settings 658
Cirrhosis 659
Major Hepatic Surgery 660
Liver Transplantation 660
Conclusion 663
References 663
Acute-on-Chronic Liver Failure in Cirrhosis: Defining and Managing Organ Dysfunction 667
Introduction 667
Defining Acute-on-Chronic Liver Failure 667
Quantifying Organ Dysfunction in Cirrhosis 668
Pathogenesis 669
Associated Organ Dysfunction 671
Adrenal 671
Brain 671
Blood (Coagulopathy) 673
Cardiovascular 673
Gut/nutrition 674
Immune System 675
Muscle/metabolic 675
Portal Hypertension/variceal Bleeding 675
Renal 676
Respiratory 677
Conclusion 677
References 678
How does Intra-abdominal Pressure Affect the Daily Management of My Patients? 638
Introduction 638
Definitions 638
Epidemiology and Etiology 639
Techniques for IAP Measurement 640
Transvesical IAP Measurement 640
Transgastric IAP Measurement 641
Recommendations for IAP Measurement 641
Should I Measure IAP in all Patients? 641
What Technique should I Use? 641
What Frequency? 641
When Should I Stop IAP Measurement? 641
The Impact of IAH on Organ Function Management 643
Effect on Cardiovascular Management 643
Effects of IAH on Respiratory Management 646
The Effect of IAH on Renal Function Management 646
The Effect of IAH on the Management of the Patient with Intracranial Hypertension 647
The Influence of IAH on the Management of Specific Patient Groups 648
IAH and Patients with Severe Sepsis 648
IAH and the Burn Patient 648
IAH and the Hematology Patient 649
IAH in Morbidly Obese Patients 649
A New Concept: Acute Bowel Injury and Acute Intestinal Distress Syndrome 649
Conclusion 650
References 651
XVI Nutrition 681
The Curse of Overfeeding and the Blight of Underfeeding 682
Introduction 682
Energy Requirements in the Critically Ill 682
Is it Better to Underfeed? 683
Underfeeding is also a problem 684
Parenteral versus Enteral Nutrition 684
Why then should there be a Link between Nutritional Excess and Infection? 685
Tight Glycemic Control and Nutrition Delivery are Linked 686
Conclusion 688
References 688
Enteral Feeding during Circulatory Failure: Myths and Reality 690
Introduction 690
Splanchnic Consequences of Feeding and of Circulatory Failure 691
Nutritional Status of the Cardiac Patient 692
Energy Target and Substrate Requirements 693
Enteral Feeding Route 693
Enteral Access 695
Timing: Preoperative, Early or Conventional Feeding 695
Enteral, Intravenous, or Combined Nutrition? 696
Patient Monitoring 697
Conclusion 698
References 699
Enteral Nutrition with Anti-inflammatory Lipidsin ALI/ARDS 702
Introduction 702
EPA and GLA Mechanisms of Action 702
From Bench to Bedside: Using EPA and GLA to Modulate Inflammation 705
Is the Evidence Enough to Change Practice? 707
Conclusion 709
References 709
Glutamine Supplementation in ICU Patients 712
Introduction 712
Background 713
Metabolic Tolerance 714
Intravenous Glutamine Supplementation during Continuous Renal Replacement Therapy 715
Glutamate Concentration and Exchange across the Brain in Head Trauma Patients 716
Endogenous Glutamine Rate of Appearance 716
General Comments 718
Conclusion 719
References 719
XVII Glucose Control 723
Burn Causes Prolonged Insulin Resistance and Hyperglycemia 724
Introduction 724
Metabolic Changes following Severe Burn Injury 724
Attenuation of the Hypermetabolic Response and Associated Hyperglycemia Post-burn 726
Molecular Mechanisms underlying Insulin Resistance Post-burn 727
Conclusion 730
References 730
Glucose Variability in Critically Ill Patients 733
Introduction 733
Glucose Elevation versus Variability 734
Defining Glucose Variability 735
Contributors to Glucose Variability 736
Evidence of Harm in Critically Ill Patients 737
Future Directions 739
Conclusion 740
References 740
XVIII Adrenal Function 743
Corticosteroid Biology in Critical Illness:Modulatory Mechanisms and Clinical Implications 744
Introduction 744
Activation of the HPA Axis 744
Transport of Cortisol in the Serum by Cortisol Binding Globulin 746
CBG and Biochemical Testing of the HPA-Axis 747
Cellular Activation and Inactivation of Cortisol by 11 HSD-1 and -2 748
The Glucocorticoid Receptor 749
Effects of Glucocorticoid Receptor Ligation 750
Importance of Steroid Responsiveness in the Etiology of Sepsis and SIRS 751
Conclusion 753
References 753
Corticosteroid Treatment of Patients in Septic Shock 756
Introduction 756
High-dose Steroid Studies 756
Low-dose Steroid Studies 757
The Corticus Study 758
Adverse Effects of Steroids 759
The Ongoing Controversy 759
Mechanism of Corticosteroid Action in Reversing Shock 760
Recommendations 760
Conclusion 761
References 762
XIX Coagulation 764
New Anticoagulants: Anti-IIa or Anti-Xa Agents? 765
Introduction 765
Factor Xa Inhibitors 765
Injectable Indirect Factor Xa Inhibitors 766
Oral Direct Factor Xa Inhibitors 768
Oral Inhibitors of Activated Thrombin (Factor IIa) 768
Conclusion 769
References 769
Emergency Reversal of Anticoagulants 771
Introduction 771
Heparin and Low Molecular Weight Heparin (LMWH) 772
Pentasaccharides 773
Vitamin K Antagonists 774
New Anticoagulants 776
Aspirin 778
Thienopyridine Derivatives and Other Antiplatelet Agents 778
Conclusion 779
References 779
XX Neurological Aspects 782
Monitoring and Managing Raised Intracranial Pressure after Traumatic Brain Injury 801
Introduction 801
ICP Monitoring 801
Techniques 801
Indications 802
Variations in Practice 802
Treatment of Intracranial Hypertension 803
Sedation and Analgesia 803
Hyperventilation 803
Hyperosmolar Therapy 803
Moderate Hypothermia 804
Barbiturates 804
Neurosurgical Interventions 804
Controversies 805
What is the Target ICP? 805
Does ICP Monitoring and Management Improve Outcome? 805
Complications of Treatment 806
Multimodal Monitoring 806
Conclusion 806
References 807
Sepsis-associated Encephalopathy 809
Introduction: Incidence and Diagnosis 809
Pathophysiology 810
Brain Signaling in Sepsis 810
Alteration of Neurotransmission 810
Mitochondrial Dysfunction, Oxidative Stress and Apoptosis 811
Endothelial Activation and Blood-brain Barrier Breakdown 812
Experimental Therapeutic Approach 812
Conclusion 814
References 814
The Role of Imaging in Acute Brain Injury 783
Introduction 783
Brain Imaging Modalities 783
Structural Imaging 783
Hemodynamic and Metabolic Imaging 785
Functional Brain Imaging 788
Applications of Imaging in Acute Brain Injury (Table 1) 788
Traumatic Brain Injury 788
Aneurysmal Subarachnoid Hemorrhage 792
Anoxic-ischemic Encephalopathy 793
Hepatic Encephalopathy 794
Sepsis-associated Encephalopathy 795
Outcome Prediction 796
Traumatic Brain Injury 796
Anoxic-ischemic Encephalopathy 796
Conclusion 797
References 797
XXI Malignancies 817
Acute Tumor Lysis Syndrome: Diagnosis and Management 818
Introduction 818
Pathophysiology 818
Diagnosis, Classification, and Risk Factors 820
Treatment 821
Fluid Expansion 822
Urine Alkalinization 822
Hypouricemic Agents 822
Prevention of Nephrocalcinosis 823
Indication and Timing of Renal Replacement Therapy 823
Management of Cancer Chemotherapy in Patients with Tumor Lysis Syndrome 823
Future Research 824
Conclusion 824
References 825
Life-threatening Neurological Complications in Patients with Malignancies 827
Introduction 827
Direct Involvement of the Nervous System by the Malignancy 827
Infiltration of the Brain Parenchyma 827
Cerebral and Epidural Metastases 828
Carcinomatous Meningitis 829
Tumors of the Peripheral Nervous System 829
Indirect Involvement of the Nervous System by the Malignancy 830
Autologous and Allogeneic Bone Marrow Transplant Recipients 830
Infections 830
Cerebrovascular Disease 831
Neurological Paraneoplastic Syndromes 833
Iatrogenic Events 836
Metabolic Complications 839
Diagnostic Strategy in Cancer Patients with New Neurological Manifestations 840
Conclusion 841
References 841
Should We Admit Critically Ill Cancer Patients to the ICU? 844
Introduction 844
Outcome in Critically Ill Cancer Patients Requiring Advanced Life Supporting Therapy 845
Reasons for Improvement in Outcomes and the Role of Non-invasive Ventilation 847
Prognostic Indicators: Subgroups with a Better and Worse Outcome 848
Triage Decisions in an Individual Patient and the Importance of Good Communication 851
Conclusion 852
References 852
XXII Drug Dosing 855
Optimizing Drug Dosing in the ICU 856
Introduction 856
Pharmacokinetic and Pharmacodynamic Alterations in Critically Ill Patients 856
Pharmacokinetic Alterations 856
Alterations in Excretion 859
Pharmacodynamic Alterations 859
Pharmacokinetic and Pharmacodynamic Modeling 860
Back to Basics 860
Bayesian Forecasting 860
Population Pharmacokinetics/pharmacodynamics 861
Application to Critically Ill Patients 863
Conclusion 864
References 864
Relevant CYP450-mediated Drug Interactionsin the ICU 867
Introduction 867
The Role of CYP450 in Drug Metabolism 867
Inhibition and Induction 868
Interindividual Variability in CYP450-mediated Metabolism 868
Relevant CYP450-mediated Interactions in the ICU 869
Drug Interactions Involving CYP3A4 869
Drug Interactions involving CYP2C9 and CYP2C19: Phenytoin and Warfarin 871
Drug Interactions Involving CYP2D6 871
Future Perspectives 872
Conclusion 872
References 873
XXIII Sedation and Analgesia 875
Sedation and Pain Management in the ICU 876
Introduction 876
The Need for Sedation or Analgesia in the ICU 876
Management of Pain 877
Anxiolysis 878
Delirium 878
Choice of Agent 879
Monitoring of Sedation 882
Cognitive Function Evaluation 883
Physiological and Brain Functional Monitors 883
Classes of Sedative Agents 884
Narcotics (Opioids) 884
Benzodiazepines 888
Alpha2 Agonists 891
Neuroleptics/‘antipsychotics’ 893
Propofol 895
Conclusion 897
References 898
The Role of Dexmedetomidine in Intensive Care 901
Introduction 901
Mechanism of Action 901
Pharmacokinetics 902
General Pharmacodynamics 902
Cardiorespiratory Effects 902
Respiratory Effects 902
Central Nervous System Effects 902
Gastrointestinal and Other Effects 903
Interactions 903
Dosage and Duration of Administration 903
Sedative and Analgesia Profile 904
Post-surgical Patients 904
Medical Patients 905
Respiratory Profile 905
Non-sedative Use in the ICU 906
Safety Profile/adverse Events 907
Conclusion 907
References 908
Monitoring Delirium in the ICU 910
Introduction 910
Burden of Illness 910
Concept 910
Occurrence Rate 912
Risk Factors 913
Cost and Consequences 914
Screening 914
Available Tools 915
Conditions for Screening Programs 918
Interventions 919
Prevention and Therapy 919
Implication for Research and Policy Information 921
Conclusion 923
References 923
XXIV ICU Management 927
Intensive Care for the Elderly: Current and Future Concerns 928
Introduction 928
Current Provision of Intensive Care 929
Definition of Elderly 929
Current Age Distribution of Intensive Care Patients 929
Caring for the Elderly 929
Triage Decisions 929
Co-morbidities 930
Mechanical Ventilation for Elderly Patients 930
Life after Intensive Care 931
Caregiver Burden 931
End-of-life Decisions 931
Future of Intensive Care for the Elderly 932
Conclusion 934
References 934
ICU Performance: Managing with Balanced Scorecards 937
Introduction 937
What is ICU Performance? 938
Outcomes 938
Patient Safety 939
Cost and Resource Utilization 939
Workforce Performance 939
Leadership Performance 939
The ICU environment 940
What is the Balanced Scorecard 940
Balanced Scorecards in Healthcare Organizations 942
Balanced Scorecard Application in the ICU 942
ICU Workforce Learning and Growth Perspective 944
ICU Internal Process and Operation Efficiency Perspective 945
ICU Patient Perspective 946
ICU Resource Utilization Perspective 946
ICU Financial Perspective 946
Successful Implementation of an ICU Balanced Scorecard System 947
Conclusion 947
References 949
XXV End-of-Life Issues 951
Towards a Neuro-scientific Explanation of Near-death Experiences? 952
Introduction 952
Near-death Experiences 953
Definition 953
Theoretical Approaches: Spiritual, Psychological and Organic Hypotheses 954
Clinical Studies 956
Out-of-body Experiences 957
Definition 957
Neuroanatomical Correlates 957
Conclusion 958
References 959
Managing Conflict at the End-of-Life 960
Introduction 960
Strategies to Prevent Conflict at the End-Of-Life 961
Community Awareness and Advance Directives 961
Futility 961
Strategies to Avoid Conflict in Acute Hospitals Before Admission to the ICU 961
Communication 962
Clinical Practice Guidelines for End-of-Life Care and Decision Making 963
Cultural, Religious and Racial Aspects around End-of-Life Conflicts 963
Direct Interventions Dealing with Conflict at the End-of-Life 963
Striving For Consensus 965
The Role of Ethical Guidelines in Conflict Resolution 965
Mediation 966
The Legal System 967
Conclusion 968
References 968
Strengths and Weaknesses of Substitute Decision Making in the ICU 970
Introduction 970
Strengths for the Patient (Table 1) 970
Substitute Decision-Making Is a Substitute for the Paternalism Model 970
Substitute Decision-Making is a Substitute for Advance Directives 971
Substitute Decision-making is the Wish of ICU Patients 971
Substitute Decision-making is a Real-time Decisional Process 972
Weaknesses for the Patient (Table 1) 972
The Designation of a Substitute Decision-maker is Problematic 972
Substitute Decision-making is not Appropriate for all Patients 972
Strengths for the Surrogate (Table 1) 972
Substitute Decision-making is the Wish of the Family 973
Weaknesses for the Surrogate (Table 1) 973
Substitute Decision-making is Dependent on Information 973
The Substitute Decision-maker is not always Objective 974
The Substitute Decision-maker can lack Capacity 974
Strengths for the Medical Team (Table 1) 975
Substitute Decision-making is the Wish of ICU Staff Members 975
Substitute Decision-making Requires Communication with the Family 975
Weaknesses for the Medical Team (Table 1) 975
The Substitute Decision-maker Requires an Assessment of Capacity 975
Substitute Decision-making is an Interpretation also for Physicians 976
Strengths for the Community (Table 1) 976
Weaknesses for the Community (Table 1) 976
Conclusion 976
References 977
Subject Index 980