Management of Dysregulated Immune Response in the Critically Ill

Description

This book, part of the European Society of Intensive Care Medicine (ESICM) textbook series, deals with dysregulated host response a relatively new term introduced by the Sepsis-3 definitions in 2016. In contrast to systemic inflammatory response syndrome (SIRS) that has been used for nearly 30 years, this is a fundamentally new concept, which requires some sort of a paradigm shift in the way of thinking of critical care physicians. This change obviously requires time and after 5 years, time is ripe to summarize the knowledge in the form of a comprehensive book. The book is split in 4 sections. In the first one, the host immune response is explained in 11 chapters, followed by the next part, summarizing the possible tools for assessment at the bedside. The third and the fourth parts focus on the effects of dysregulated immune response on vital organ function and on the possible ways of immunomodulation. Written by internationally acclaimed experts of the field, the book is of value for all those intensivists and allied professionals working in ICUs. Foreword Preface Contents Contributors I: The Host Immune Response 1: Phenotypes 1.1 Introduction: The Critically Ill, a Heterogeneous Population 1.2 Subphenotypes Identified in Critically Ill Patients 1.2.1 Sepsis 1.2.2 Acute Respiratory Distress Syndrome 1.2.3 Acute Kidney Injury 1.2.4 Implications of Identified Subphenotypes 1.3 The Immune Response in Subphenotypes 1.3.1 Innate Immune Response 1.3.2 Adaptive Immune Response 1.3.3 Implications of the Immune Response in Subphenotypes 1.3.4 Unique or Generalizable? 1.4 Future Challenges References 2: The Dysregulated Host Response 2.1 Introduction 2.2 The Inflammatory Response in Severe Infection 2.3 The Immune Depression in Sepsis (Early and Late Phase) 2.3.1 The Immune Phases 2.3.2 The “Downregulation” of Monocyte/Macrophages 2.3.3 The Immunodepression and Adaptive Immunity 2.3.4 The Proteomic Consequences 2.4 The Role of Cellular Metabolism 2.4.1 The Aerobic Glycolysis or “Warburg Effect” (. Fig. 2.2 [57]) 2.4.2 The Hypoxia-Inducible Factor (HIF) 2.4.3 The Regulation of the Immune Response by mTOR [68] 2.4.4 The Combination of Mediated mTOR and HIF-1α Aerobic Glycolysis: A Basis for Trained Immunity [3, 5] (. Fig. 2.4) 2.4.5 The Liaison Between Metabolic Shift Modifications and Functions of Immune Cells Conclusion and Road Map for the Future References 3: What Is Cytokine Storm? 3.1 Introduction 3.2 Pathophysiology of CS 3.3 Inflammation Due to Sepsis 3.4 Hypercytokinemia in Sepsis 3.5 Hypercytokinemia in Post-cardiac Arrest Syndrome 3.6 Endotoxin-Induced CS 3.7 CS After Splenectomy 3.8 Invasive Meningococcal Disease (IMD) 3.9 COVID-19 3.10 Iatrogenic CS 3.11 After the Storm 3.12 Summary References 4: Hemophagocytic Lymphohistiocytosis 4.1 Introduction 4.2 Types 4.3 Epidemiology 4.4 Triggers and Underlying Conditions 4.5 Pathobiology 4.6 Clinical Presentation 4.7 Diagnosis 4.8 Treatment 4.9 Macrophage activation syndrome (MAS-HLH) 4.10 HLH and Sepsis 4.11 Prognosis 4.12 Summary References 5: Extracorporeal Circulation-Related Immune Response 5.1 Introduction 5.2 Extracorporeal Circulations in ICU Practice 5.2.1 Renal Replacement Therapy 5.2.2 ECMO 5.3 Extracorporeal Circulation-Related Immune Response and the Clinical Implications 5.3.1 Contact and Complement System Contact System Complement System 5.3.2 Inflammatory Cytokine and Chemokine Response 5.3.3 Leukocytes Impact on the Innate Immune Leukocytes: Neutrophils and Monocytes Impact on Neutrophil Phenotype and Function Impact on Monocyte Phenotype and Function Impact on the Adaptive Immune Leukocytes: T and B Lymphocytes Impact on T and B Lymphocyte Phenotype and Function 5.4 Causes of Extracorporeal Circulation-Related Immune Response 5.4.1 RRT and ECMO Technology (ECC Circuit Designs and Materials) Blood Pumps Membranes RRT Filter Membranes ECMO Membrane Oxygenator 5.4.2 Non-physiological Conditions 5.5 Priorities for Future Research: Potential Therapeutic Interventions in ECC-Associated Immune Response 5.5.1 Knowing the Technological Disparities 5.5.2 Understanding Factors Contributing to RRT- and  ECMO-Related Immune Modulation 5.5.3 Potential Interventions and Targets for RRT- and  ECMO-Related Immune Modulation References 6: Septic Shock 6.1 Introduction 6.2 Of Infection, Mediators, and Vasodilation 6.3 Parameters of Tissue Perfusion in Early Resuscitation 6.3.1 Blood Pressure 6.3.2 Lactate Levels 6.3.3 Central Venous Oxygen Saturation (ScvO2) 6.3.4 Central Venous to Arterial PCO2 Difference (dPCO2) 6.3.5 Peripheral Perfusion 6.3.6 Holistic Approach 6.4 On the Use of Fluids 6.4.1 The Physiology 6.4.2 On the Volume of Fluids 6.5 On the Use of Vasoactive Medication 6.5.1 Vasopressors Norepinephrine Vasopressin Phenylephrine Other Vasoplegia in the Context of Decreased Vasoresponsiveness 6.5.2 Inodilators Dobutamine Use of Alternative Inotropes 6.5.3 Mitigating the Adrenergic Response References II: Assessing Dysregulated Immune Response at the Bedside 7: Pro- and Anti-inflammatory Biomarkers 7.1 Introduction 7.2 Pro- and Anti-inflammatory Biomarkers 7.3 Separating Pro- and Anti-inflammatory Biomarkers? 7.4 Combining Cytokine Levels? 7.5 Clinical Applications of Biomarkers References 8: How to Interpret Procalcitonin? 8.1 Introduction 8.2 Evidence Regarding PCT-Guided Antibiotic Stewardship 8.3 Practical Considerations for Use of PCT 8.4 Limitations of Procalcitonin References 9: Assessment of the  Macro- and Microcirculation 9.1 Introduction 9.2 Coupling Macro- and Microcirculation: Monitoring Peripheral Perfusion in Critically Ill Patients 9.2.1 Role of Blood Lactate 9.3 Clinical Assessment of Peripheral Perfusion 9.3.1 Role of the Capillary Refill Time 9.4 Peripheral Perfusion Assessed by Skin Functional and Clinical Assessment 9.4.1 Skin Temperature and Mottling 9.5 Optical Monitoring 9.5.1 Peripheral Perfusion Index 9.5.2 Near-infrared Spectroscopy 9.5.3 Assessment of Microvascular Perfusion References III: Dysregulated Immune Response and Organ Dysfunction 10: Management of Dysregulated Immune Response in the Critically Ill: Heart and Circulation 10.1 Inflammation in Cardiovascular Diseases 10.1.1 The Central Role of Cytokines in Inflammation During Cardiovascular Diseases 10.1.2 The Pivotal and Critical Role of NLRP3 Inflammasome in Acute Myocardial Infarction (AMI) 10.2 Inflammation in Septic Cardiomyopathy 10.3 Inflammation and Cardiac Arrhythmias 10.4 Inflammation in Acute Heart Failure and Cardiogenic Shock 10.5 Inflammation and Vascular System 10.5.1 Endothelial Dysfunction 10.5.2 Glycocalyx Breakdown 10.5.3 Junction Protein Dysregulation 10.6 Long-Term Impact of Critical Care on Cardiovascular Health: Immune Scar 10.7 Therapeutic Approach of Inflammation During CVD 10.7.1 Anakinra 10.7.2 Colchicine Anti-inflammatory Mechanisms Therapeutic Benefits 10.7.3 Steroids Conclusion References 11: Brain 11.1 Introduction 11.2 Epidemiology 11.3 Pathophysiology 11.4 Biomarkers to Measure Neuroinflammation 11.5 Neuroinflammation in Systemic Inflammatory Conditions 11.6 Future Perspectives References 12: Dysregulated Immune Response and Kidney Dysfunction 12.1 Introduction 12.2 Normal Physiology 12.3 Acute Kidney Injury 12.3.1 Endothelial Dysfunction 12.3.2 Microcirculatory Dysfunction 12.3.3 Tubular Cell Injury 12.3.4 Intrarenal Inflammation 12.4 Additional Factors Contributing to Inflammation in AKI 12.4.1 Haemodynamic Instability 12.4.2 Renal Venous Congestion 12.4.3 Tubular Obstruction 12.4.4 Hypersensitivity Immune Reactions 12.5 AKI Sub-types 12.6 Organ Crosstalk 12.7 Renal Repair/Progression 12.8 Management References 13: Dysregulated Immune Response and Organ Dysfunction: Liver 13.1 Introduction 13.2 Immune Competent Cells of the Liver and Their Function 13.2.1 Hepatic Lymphocytes 13.2.2 Myeloid Cells in the Liver 13.2.3 Liver Sinusoidal Endothelial Cells 13.2.4 Hepatic Stellate Cells 13.2.5 Hepatocytes 13.3 Liver Impairment in Patients with Critical Illness 13.4 The Liver in Systemic Inflammation and Sepsis 13.5 Management of Liver Failure in Critical Illness 13.6 Targeting Immune Dysregulation in Liver Disease References 14: Hemostasis 14.1 Introduction 14.2 The Pathophysiology of Inflammation-Induced Coagulopathy 14.2.1 Normal Hemostasis 14.2.2 Inflammation-Induced Alterations in the Coagulation System 14.3 Specific Forms of Inflammation-Induced Coagulopathy 14.3.1 Disseminated Intravascular Coagulation 14.3.2 Sepsis-Induced Coagulopathy (SIC) 14.3.3 Malignancy-Associated DIC 14.3.4 Obstetric Associated DIC 14.3.5 COVID-Associated Coagulopathy: An Exception to this Chapter 14.3.6 Trauma-Induced Coagulopathy (TIC) 14.4 Diagnosis of Inflammation-Induced Coagulopathy 14.4.1 Disseminated Intravascular Coagulation 14.5 Viscoelastic Tests in the Diagnosis of Inflammation-Induced Coagulopathy 14.6 Clinical Consequences of Inflammation-Induced Coagulopathy 14.6.1 Risk of Bleeding: Incidence and Risk Factors 14.6.2 Risk of Thromboembolic Events: Incidence and Risk Factors 14.6.3 Organ Failure 14.6.4 Mortality 14.7 Prevention of Bleeding in Inflammation-Induced Coagulopathic Patients 14.7.1 Prophylactic Platelet Transfusion 14.7.2 Prophylactic Plasma Transfusion 14.7.3 Tranexamic Acid 14.7.4 Prevention of Bleeding in Coagulopathic Patients Undergoing an Invasive Procedure 14.7.5 Treatment of Bleeding in Inflammation-Induced Coagulopathic Patients 14.8 Clinical Management of Risk of Thrombosis 14.8.1 Pharmacological Thromboprophylaxis 14.8.2 Type of Pharmacological Thromboprophylaxis 14.9 Management of Patients with DIC 14.9.1 Anticoagulant Treatment of (Micro)thrombotic Events 14.9.2 Substitution of Anticoagulant Proteins 14.10 Treatment of Thrombosis in Inflammation-Induced Coagulopathy References 15: Dysregulated Immune Response and Organ Dysfunction: The Muscles 15.1 Introduction 15.2 Critical Illness-Associated Muscle Wasting 15.3 Muscle Metabolism and Mitochondrial Dysfunction in Critical Illness 15.4 Immune Dysfunction in Critical Illness 15.4.1 Persistent Inflammation, Immunosuppression, and Catabolism Syndrome 15.4.2 Intramuscular Inflammation, Mitochondrial Dysfunction, and Myocyte Necrosis Systemic Inflammation as a Cause for Necrosis Mitochondrial Dysfunction as a Cause of Myocyte Necrosis 15.4.3 So Which Mechanism Predominates? References IV: Modulating the Immune Response 16: The Role of Steroids 16.1 Introduction 16.2 Pathophysiology of Sepsis Relevant to Corticosteroids 16.3 Should Glucocorticoids Be Used in Sepsis? 16.4 When and How to Administer Glucocorticoids in Septic Shock 16.4.1 When Should Steroids Be Administrated in Septic Shock? 16.4.2 What Dose of Steroids Should Be Administered? 16.4.3 Should Fludrocortisone Be Associated with Hydrocortisone? 16.4.4 What Is the Optimal Duration of Glucocorticoid Administration? 16.4.5 Should Glucocorticoids Be Tapered Off? 16.4.6 What Are the Main Side Effects of Steroids? 16.4.7 Should Other Conditions Be Treated by Glucocorticoids in the ICU? 16.4.8 Can Glucocorticoid Treatment Be Personalized in Sepsis? References 17: Anti-cytokine Therapy in Critical Illness: Is There a Role? 17.1 Introduction 17.2 Cytokines in the Regulation of a Systemic Response to Danger: A Historical Perspective 17.2.1 Cytokines and Hormones: How Do They Differ? 17.2.2 Cytokines: An Evolving Understanding 17.2.3 How Do Cytokines Alter Cellular Functioning? 17.3 Cytokine-Targeted Therapy in Chronic Inflammatory Diseases 17.3.1 Rheumatoid Arthritis 17.3.2 Other Autoimmune Disorders 17.3.3 Inflammatory Bowel Disease 17.3.4 Oncology 17.3.5 Other Diseases 17.4 Targeting Cytokines in Acute Inflammatory Diseases 17.4.1 Preclinical Insights 17.4.2 Insights from Clinical Trials in COVID-19 17.5 Cytokine-Targeted Therapy in Sepsis 17.5.1 The Story So Far 17.6 Why Have Clinical Trials of Anti-cytokine Therapy for Sepsis Been So Disappointing? 17.6.1 Sepsis Is Intrinsically Heterogeneous 17.6.2 The Innate Immune Response Is Vital to Effective Anti-infectious Host Defense 17.6.3 The Host Innate Immune Response Is Biologically Redundant 17.6.4 Preliminary Evaluation of Potential Strategies Is Often Inadequate 17.6.5 Mortality Endpoints Are Insensitive to Potential Benefits 17.6.6 Timing, Dose, and Duration of Treatment Are Poorly Understood 17.6.7 The Study Model Is Ill-Adapted to Understand the Reasons for Failure 17.6.8 Sepsis Lacks Effective Systems for Staging and Stratification References 18: Extracorporeal Cytokine Removal 18.1 Introduction 18.2 High-Flux and High-Cutoff Hemofilters 18.3 Adsorptive Hemofilters 18.4 Dedicated Hemoadsorption Columns 18.5 Combined Plasma Filtration and Adsorption or Therapeutic Plasma Exchange 18.6 Summary References