Peri-operative Anesthetic Management in Liver Transplantation

The book covers all aspects of peri-operative anesthetic management of liver transplant patients. It provides a comprehensive coverage of the relevant history, surgeons’, hepatologists’, intensivists’ and pediatricians’ perspective of the disease, its pathogenesis, clinical presentation and indication for transplant. It discusses the practical aspects like fluid management and use of vasopressors. The book is divided into sections for a better and comprehensive delivery of information. Individual sections provide up to date information on the pre-operative issues and optimisation, intra-operative care and management and post-operative critical care issues and management of all transplant patients with special emphasis on recent advances. Separate sections cover ICU care of these patients in great detail and anesthetic management of pediatric liver transplant. The book includes anesthetic techniques involved in conducting multiorgan transplant. It discusses clinical approach to a patient with acute liver failure, brain death criteria and laws and organ donor management. It also presents newer techniques and methodologies adopted in the field of liver transplant. It includes ample illustrations, flowcharts, key points in each chapter, figures and photographs. The book contains chapters focusing on post-transplant patients presenting for non-transplant surgery. The book fills the gap in the literature for a comprehensive guide for the anesthetist performing or pursuing liver transplant, students/trainees/examinees who have a keen interest in this field and doctors dealing with such patients in critical care, donor management, pursuing general anesthesia. It is also helpful for hepatologists, intensivists and surgeons associated with liver transplant. Preface Contents About the Editors 1: The History of Liver Transplantation in India 1.1 Introduction 1.2 Background 1.3 Step I: Public Education 1.4 Step 2: Changing the Law 1.5 Step 3: The Initial Procedures 1.6 Step 4: Sustainable Programmes 1.6.1 Numbers 1.6.2 Statewise Distribution 1.6.3 The Situation in 2020 1.7 India Vs the World 1.8 Concerns 1.9 Recommendations 1.10 Conclusions Part I: Basics Anatomy and Pathophysiology of Liver Disease 2: Physiological Role of Liver and Interpreting Liver Function Tests 2.1 Gross Anatomy of the Liver 2.1.1 Hepatic Blood Flow Regulation 2.2 Cellular Anatomy of the Liver 2.2.1 Models of Liver Microanatomy 2.3 Liver, the Immunological Gateway 2.3.1 Innate and Adaptive Immunity 2.3.2 Immune Tolerance 2.4 Hepatic Drug Metabolism 2.4.1 First Pass Effect 2.4.2 Phases of Drug Metabolism 2.4.3 Drug Extraction Ratio 2.5 Energy Metabolism 2.5.1 Glucose Homeostasis 2.5.2 Nitrogen Metabolism 2.5.3 Fatty Acid Metabolism 2.6 Role of the Liver in Coagulation 2.7 Hepatic Endocrine Function 2.8 Chronic Liver Disease 2.9 Interpreting Liver Function Tests 2.10 Tests Detecting Hepatocyte Injury 2.10.1 Serum Aminotransferases 2.10.2 AST to ALT Ratio 2.10.3 Lactate Dehydrogenase 2.11 Tests Detecting Injury to Bile Ducts 2.11.1 Alkaline Phosphatase 2.12 5′-Nucleotidase 2.13 Gamma-Glutamyl Transferase 2.14 Tests Assessing Biliary Organic Anion Transport 2.14.1 Serum Bilirubin 2.15 Tests Measure Hepatic Synthetic Capacity 2.15.1 Serum Proteins 2.16 Prothrombin Time and International Normalized Ratio 2.17 Tests Measuring Blood Flow and Metabolic Capacity of Liver 2.18 Pattern of Liver Test Abnormalities 2.19 Monitoring Liver Transplant References 3: Surgical Anatomy of the Liver 3.1 Introduction 3.2 Ligaments of the Liver (Fig. 3.1) 3.2.1 Ligamentum Venosum (Arantius Ligament) 3.3 Lobar and Segmental Anatomy of the Liver 3.3.1 Functional Surgical Anatomy of the Liver 3.3.2 Bismuth’s Liver Segmentation 3.4 Caudate Lobe 3.4.1 Hepatocaval Ligament (Makuuchi Ligament) 3.4.2 Riedel Lobe (Fig. 3.8) 3.5 Hepatic Veins (Venous Outflow) 3.5.1 Right Inferior Hepatic Veins: RIHV (Fig. 3.11) 3.5.2 Inferior Phrenic Veins 3.6 Anatomical Relations Around the Hilum 3.6.1 Extrahepatic and Intrahepatic Vasculature 3.7 Portal Vein 3.8 Hepatic Artery 3.9 Biliary Anatomy 3.9.1 Intrahepatic Bile Duct Anatomy 3.9.2 The Right Hepatic Duct 3.9.3 The Left Hepatic Duct 3.9.4 Extrahepatic Biliary Anatomy 3.9.5 Biliary Ductal Anomalies 3.9.6 Bile Duct Blood Supply 3.10 Gallbladder and Cystic Duct 3.10.1 The Calot’s Triangle (Fig. 3.19) References 4: Pathophysiology of Chronic Liver Disease 4.1 Introduction 4.2 Cellular Anatomy of the Liver 4.3 Etiology of Chronic Liver Disease 4.4 Pathophysiology of Chronic Liver Disease 4.4.1 Basics of Liver Inflammation 4.4.2 Cells Involved in Liver Inflammation 4.4.3 Repair of the Damaged Liver 4.5 Cirrhosis and Portal Hypertension 4.5.1 Hemostasis 4.5.2 Cardiac Manifestations 4.5.3 Renal Dysfunction 4.5.4 Pulmonary Complications 4.5.5 Hepatic Encephalopathy 4.5.5.1 Ammonia Hypothesis 4.5.5.2 Impaired Neurotransmission Hypothesis 4.5.6 Ascites 4.5.7 Varices References 5: Pharmacokinetics and Pharmacodynamics of Drugs in Liver Disease 5.1 Introduction 5.2 The Normal Liver 5.3 Role of Liver in Drug Metabolism 5.4 Consequences of Liver Disease on Pharmacokinetics 5.5 Drug Absorption 5.6 Plasma Protein Binding and Drug Distribution 5.7 Metabolism 5.8 Biliary Excretion 5.9 Drugs Undergoing Renal Excretion 5.10 Consequences of Liver Disease on Pharmacodynamics 5.11 Assessment of Liver Function 5.12 Child-Pugh Scoring System 5.13 Conclusion References 6: Viral Markers and Their Relevance in Liver Disease and Transplantation 6.1 Introduction 6.2 Hepatitis A Virus (HAV) 6.3 Hepatitis E Virus (HEV) 6.4 Hepatitis B Virus (HBV) 6.4.1 Epidemiology 6.4.2 Transmission 6.4.3 Serology/Serological Markers 6.4.4 Occult Hepatitis B Infection (OBI) 6.4.5 Transplantation for Hepatitis B 6.4.5.1 Risk Factors for HBV Recurrence after Liver Transplant 6.4.5.2 Prophylaxis for Prevention of Hepatitis B Virus (HBV) Graft Recurrence Following Liver Transplantation Antiviral Monotherapy 6.4.5.3 Prophylaxis for Prevention of Hepatitis B Virus (HBV) Graft Recurrence Following Liver Transplantation (LT) Combination Prophylaxis 6.4.6 Antiviral Monotherapy 6.5 Hepatitis D Virus (HDV) 6.5.1 Laboratory Diagnosis 6.5.2 Liver Transplantation in Patients with Hepatitis D Virus Liver Cirrhosis 6.6 Hepatitis C Virus (HCV) 6.6.1 Epidemiology 6.6.2 Clinical Features 6.6.3 Diagnosis 6.6.4 Screening Test: (Anti-HCV Antibody) 6.6.5 Treatment Strategies and End-Stage Liver Disease 6.6.6 Liver Transplantation for HCV-Related Liver Disease 6.6.6.1 Hepatitis C Virus Infection After Liver Transplantation 6.6.6.2 Treatment Strategies for HCV 6.7 Donors with Viral Hepatitis 6.7.1 Hepatitis B Virus 6.7.2 Approach to the Isolated HbcAb-Positive Donor 6.7.3 Approach to Use of HbsAg or HBVNAT-Positive Donors 6.8 Hepatitis A and E Virus 6.9 Conclusion References Part II: Liver Transplantation: Indications, Pre-operative Assessment and Optimization 7: Indication and Contraindications for Liver Transplantation 7.1 Indications 7.1.1 Acute Liver Failure 7.1.2 Chronic Liver Disease 7.1.2.1 Viral Hepatitis 7.1.2.2 Alcoholic Liver Disease 7.1.2.3 Cholestatic Liver Disease Primary Sclerosing Cholangitis (PSC) Inclusion Criteria for Liver Transplantation in PSC Exclusion criteria for Liver Transplantation in PSC Primary Biliary Cirrhosis (PBC) 7.1.2.4 Malignancy Hepatocellular Cancer (HCC) Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Hilar Cholangiocarcinoma (H-CCA) Metastatic Neuroendocrine Tumours 7.1.2.5 LT in Metabolic Liver Disease 7.1.2.6 Vascular Causes 7.2 Liver Transplantation in Paediatric Patients 7.3 Contraindication 7.4 Contraindications for Live Liver Donors as per OPTN (Organ Procurement and Transplantation Policy) [34] 7.5 Summary References 8: Disease Severity Scoring System in Chronic Liver Disease 8.1 Introduction 8.2 Clinical States in Cirrhosis 8.3 Different Scoring Systems in Cirrhosis 8.3.1 CTP Score 8.3.2 Modified CTP Score 8.3.3 MELD Score and Its Modifications 8.3.4 Alcoholic Liver Disease 8.3.5 Primary Biliary Cirrhosis 8.3.6 Primary Sclerosing Cholangitis 8.4 Acute on Chronic Liver Failure 8.4.1 APASL AARC Definition 8.4.2 EASL CLIF-C Definition 8.4.3 CLIF-C AD Score 8.4.4 CLIF-C ACLF Score 8.5 Conclusion References 9: Preoperative Assessment and Optimization of Liver Transplant Patient: Ascites and Hydrothorax 9.1 Introduction 9.2 Pathophysiology of Ascites in Cirrhosis [4, 5] 9.3 Standard Diagnostic Steps 9.3.1 History 9.3.2 Physical Examination 9.3.3 Laboratory Assessment 9.3.4 Abdominal Ultrasound 9.3.5 Diagnostic Paracentesis 9.3.6 Analysis of Ascitic Fluid in a Cirrhotic Patient 9.4 Management: Depends on the Grade of Ascites 9.5 Management of Patient with Grade II Ascites [5, 6] 9.5.1 Diuretics 9.6 Management of Grade III Ascites/Tense Ascites 9.6.1 Refractory Ascites (RA) 9.6.1.1 Management of Patient Refractory Ascites 9.6.1.2 Large Volume Paracentesis (LVP) 9.6.1.3 Transjugular Intrahepatic Portosystemic Shunt (TIPS) 9.6.1.4 Peritoneovenous Shunt 9.6.1.5 Pharmacological Therapies 9.6.1.6 Indwelling Peritoneal Catheters 9.6.2 CART—Cell Free Concentrated Ascites Reinfusion Therapy 9.6.2.1 Peritoneal Urinary Drainage (Alfa Pump System) 9.7 Hepatic Hydrothorax 9.7.1 Uncomplicated Hepatic Hydrothorax [45] 9.7.2 Management References 10: Preoperative Assessment and Optimization of Liver Transplant Patients: Cardiac Issues in Liver Disease 10.1 Hemodynamic Changes in Patients with Cirrhosis 10.2 Preoperative Cardiac Evaluation of Liver Transplant Candidates 10.3 Systemic Disease That Affect Both Heart and Liver 10.4 Management of Stenotic CAD References 11: Preoperative Assessment and Optimisation of Liver Transplant Patients: Renal Issues 11.1 Introduction 11.2 Definition of Acute Kidney Injury 11.3 Pathophysiology of Renal Dysfunction in Liver Impairments 11.4 Evaluating Criteria 11.5 Management References 12: Preoperative Assessment and Optimization of Liver Transplant Patients: Pulmonary Issues 12.1 Introduction 12.2 Hepatopulmonary Syndrome 12.3 Epidemiology and Pathophysiology 12.4 Portopulmonary Hypertension 12.5 Epidemiology 12.6 Pathophysiology 12.7 Diagnosis 12.8 Hepatic Hydrothorax 12.9 COPD and Smoking 12.10 Obstructive Sleep Apnea 12.11 Interstitial Lung Disease 12.12 Alpha1 Antitrypsin Deficiency 12.13 Arteriovenous Malformations (AVM) 12.14 Pulmonary Nodules 12.15 Preoperative Assessment 12.15.1 History 12.15.2 Physical Examination 12.15.3 Laboratory Investigations 12.16 Management 12.16.1 HPS 12.17 Portopulmonary Hypertension 12.18 Specific Therapy 12.18.1 PAH-Specific Therapy Includes 12.19 Hepatic Hydrothorax 12.20 Summary References 13: Coagulation in Liver Disease 13.1 Introduction 13.2 Haemostasis in Health 13.3 Coagulation in Chronic Liver Disease 13.4 Coagulation in Acute Liver Failure 13.5 Procoagulant Factors 13.6 Fibrinogen 13.7 von Willebrand Factor (vWf) 13.8 Platelets 13.9 Anticoagulant Factors 13.10 Fibrinolytic and Antifibrinolytic System 13.11 Disseminated Intravascular Coagulation (DIC) 13.12 Hypercoagulability 13.13 Assessment and Correction of Coagulation Status Before Invasive Procedures 13.14 Coagulation and Infection 13.15 Portal Hypertension and Bleeding 13.16 Conclusion References 14: Nutrition in Chronic Liver Disease 14.1 Introduction 14.2 Prevalence and Causes of Malnutrition in Cirrhosis 14.3 Causes of Under-Nutrition 14.4 Screening for Malnutrition in Patients with Chronic Liver Disease 14.4.1 History 14.4.2 Physical Examination 14.4.3 Anthropometry, Biochemical Measures and Rapid Screening Tests for Nutritional Status 14.5 Assessment and Implications of Sarcopenia 14.6 Recommendations 14.7 Effect of Obesity on Cirrhosis 14.8 Summary References Part III: Intra-operative Course and Management 15: Intra-operative Management of Transplant Recipient: An Overview 15.1 Introduction 15.2 Preoperative Preparation 15.3 Preoperative Fasting Guidelines and Preparation 15.4 Conduct of Anaesthesia 15.5 Haemodynamic Monitoring 15.5.1 Central Venous Pressure (CVP) Monitors 15.5.2 Cardiac Output Monitors (Table 15.1) 15.5.2.1 Can We Derive Fluid Responsiveness? 15.5.2.2 Induction Agents 15.5.3 How Do I Intubate a Patient with CLD for Transplant? Is RSI Mandatory? 15.6 Depth of Anaesthesia Monitoring During Liver Transplant Surgery 15.7 Fluid Management in Liver Surgery 15.8 Coagulation Monitoring and Guidelines for Product Transfusion 15.8.1 Fast Tracking in Liver Transplant 15.9 Conclusion References 16: Ischemia–Reperfusion Injury 16.1 Introduction 16.2 Pathophysiology 16.2.1 Ischemia 16.2.2 Reperfusion 16.3 Global Effects of Hepatic Ischemia–Reperfusion Injury 16.4 Measures to Ameliorate Hepatic Ischemia–Reperfusion Injury 16.4.1 Pharmacological Measures 16.4.2 Surgical 16.5 Summary References 17: Hemodynamic Monitoring in Liver Transplantation 17.1 Blood Pressure 17.2 Central Venous Pressure 17.3 Invasive Cardiac Output Monitoring 17.4 Minimally Invasive Cardiac Output Monitoring 17.5 Transesophageal Echocardiography References 18: Intraoperative Coagulation Monitoring in Liver Transplant Surgery 18.1 Introduction 18.2 Intraoperative Changes in Each Phase 18.2.1 Dissection Phase 18.2.2 Anhepatic Phase 18.2.3 Post-reperfusion/Neohepatic Phase 18.3 Monitoring Coagulation During Liver Transplant Surgery 18.3.1 Standard Laboratory Tests 18.3.2 Prothrombin Time (PT) 18.3.3 International Normalized Ratio (INR) 18.3.4 Activated Partial Thromboplastin Time (aPTT) 18.3.5 Thrombin Time [13] 18.3.6 Platelet Count 18.3.7 Fibrinogen 18.3.8 Fibrinogen Degradation Products (FDPs) and D-Dimer (Tests of Fibrinolysis) 18.3.9 Limitations of Conventional Tests 18.4 Point-of-Care Coagulation Testing 18.4.1 Functional Assay of Monitoring Heparin Anticoagulation [13] 18.4.1.1 Activated Clotting Time (ACT) 18.4.2 Platelet Function Monitoring 18.4.2.1 Platelet Function Analyser-100 18.4.3 Near-Patient Clotting Factor Test 18.4.4 Viscoelastic Measures of Coagulation 18.4.4.1 TEG/ROTEM: Introduction 18.4.4.2 Thromboelastography (TEG) 18.4.4.3 Decrease in Amplitude Measurement A30 and A60 [22] 18.4.4.4 Clot Pro 18.4.5 Rotational Thromboelastometry (ROTEM) 18.4.5.1 Diagnostic Power of TEG/ROTEM [11] 18.4.6 The Sonoclot 18.4.6.1 Principle 18.4.7 Use of Standard/Conventional Tests in Liver Transplant 18.4.8 Use of Point-of-Care (POC) Devices in Liver Transplant 18.4.8.1 Pre-transplant Liver Failure Patients 18.4.8.2 Intraoperative Use of TEG During Liver Transplant 18.4.8.3 Sonoclot in Liver Transplant 18.4.8.4 Application of Platelet Function Testing in Liver Transplant [8] 18.4.9 Limitations [23] 18.5 Conclusion References 19: Fluid Therapy in Liver Transplant 19.1 Vascular Component Approach for Guiding Fluid Therapy: A Novel and Critical Way of Volume Status Assessment [16] 19.2 Restrictive vs. Liberal Strategy 19.3 Composition of Fluids and Its Impact on Outcome 19.4 Monitoring of Volume Status and Perioperative Fluid Management 19.5 Fluid Assessment in ICU 19.6 Special Considerations 19.6.1 LDLT vs. Cadaveric References 20: Role of Vasopressors in Liver Transplant Surgery 20.1 Introduction 20.2 Aetiopathogenesis 20.3 Haemodynamic Changes During LT Surgery 20.3.1 Anaesthesia-Related Factors 20.3.2 Surgery-Related Factors [1, 2] 20.4 Vasoactive Agents Used During Orthotopic Liver Transplant (OLT) [3, 4, 6] 20.4.1 Norepinephrine 20.4.2 Phenylephrine 20.4.3 Epinephrine 20.4.4 Ephedrine 20.4.5 Dopamine 20.4.6 Dobutamine 20.4.7 Isoproterenol 20.4.8 Vasopressin and Analogues 20.5 Nonadrenergic Agents 20.6 Complications of Vasopressor Use 20.7 Conclusion References 21: Minimizing Blood Loss in Recipient Surgery 21.1 Introduction 21.2 Why to Minimize Transfusion? 21.3 Coagulation Derangements (Preoperative and Intraoperative) 21.4 Risk Factors (Recipient, Surgery and Graft-Related Risk Factors) 21.5 Prevention of Excessive Bleeding 21.5.1 Nonpharmacological Interventions 21.5.2 Pharmacological Interventions 21.5.2.1 Antifibrinolytics 21.5.2.2 Prothrombin Complex Concentrate (PCC) 21.5.2.3 Fibrinogen Concentrate 21.6 Others 21.6.1 Strategies References 22: Veno-Venous Bypass in Liver Transplantation 22.1 Introduction and Historical Background 22.2 Indications for VVBP (Table 22.2) 22.2.1 Cardiovascular Instability 22.2.2 Renal Impairment 22.2.3 Acute Liver Failure (ALF) 22.2.4 Severe Portal Hypertension 22.2.5 Massive Bleeding During Hepatectomy and Other Indications 22.3 Contraindications 22.4 Insertion and Management of VVBP 22.5 Complications of VVBP (Table 22.3) 22.5.1 Vascular Access Related 22.5.2 Extracorporeal/Bypass Circuit Related 22.5.3 Post-Reperfusion Syndrome (PRS) 22.6 Caval Preserving Options 22.7 Selective Use of VVBP 22.8 Conclusion References 23: Intraoperative Complications and Management 23.1 Massive Blood Transfusion in Liver Transplant 23.1.1 Preoperative Risk Factors for Massive Blood Transfusion 23.1.2 Intraoperative Risk Factors for Massive Blood Transfusion 23.2 The Role of Graft Function 23.3 Management of Massive Blood Loss 23.3.1 Fluid Management 23.4 Maintenance of Homeostatic Conditions for Clotting 23.4.1 Vasopressors 23.5 Coagulation Tests for Monitoring and Guiding Coagulation Management 23.5.1 Pharmacological Interventions 23.5.1.1 Antifibrinolytic Drugs 23.5.1.2 Fibrinogen 23.5.1.3 Prothrombin Complex Concentrate 23.5.1.4 Recombinant Activated Factor VII 23.5.1.5 Factor XIII 23.5.2 Protamine and the Heparin Like Effect 23.5.3 Fractionated Products vs. Fresh Components 23.5.4 Preparation for Massive Bleeding 23.5.5 Transfusion of Blood Components During Massive Blood Transfusion 23.5.5.1 Fixed Ratio Blood Products Vs. POC Directed Transfusion 23.5.5.2 Targets of Resuscitation in Massive Blood Loss 23.6 Intracardiac Thrombus (ICT) and Pulmonary Embolism (PE) 23.6.1 Incidence of Intraoperative Thromboembolic Events 23.6.1.1 Predisposing Factors 23.6.1.2 Role of Antifibrinolytics 23.6.1.3 Factor Concentrates 23.6.2 Management of ICT 23.6.2.1 Anticoagulation 23.6.2.2 Suggested Management of Intra Cardiac Thrombus 23.6.3 Intraoperative Vasoplegia 23.6.4 Methylene Blue [51] 23.6.5 Air Embolism During Liver Transplantation 23.7 Severe Post-Reperfusion Syndrome (PRS) 23.7.1 Dynamic LVOT Obstruction (LVOTO) 23.7.2 Pulmonary Hypertension 23.7.2.1 Arrhythmias 23.7.2.2 Treatment 23.7.3 Miscellaneous 23.8 Conclusion References Part IV: Donor Issues: Liver Donor Hepatectomy and Organ Donation 24: Peri-Operative Assessment and Management of Live Donor for Donor Hepatectomy 24.1 Introduction 24.2 Donor Evaluation 24.2.1 Phase 1 24.2.2 Phase 2 24.2.3 Phase 3 24.3 Multidisciplinary Team Assessment 24.4 Pre-Anaesthetic Assessment 24.5 Systemic Assessment 24.5.1 Assessment Day Before Surgery (Day −1) 24.6 Anaesthetic Management 24.6.1 Transfusion Requirement and Methods of Minimizing Blood Loss 24.6.1.1 Low Central Venous Pressure (CVP) 24.6.1.2 Acute Normovolemic Hemodilution (ANH) 24.6.1.3 Pre-Operative Autologous Blood Transfusion 24.7 Post-Operative Care 24.8 Pain Management 24.8.1 Abdominal Wall Blocks 24.8.2 Multi Modal Analgesia 24.9 DVT Prophylaxis 24.10 Remnant Liver: Monitoring Its Function 24.11 Robotic Donor Hepatectomy 24.12 Liver Regeneration 24.13 Complications References 25: Brain Death and Organ Donation 25.1 Introduction 25.2 Organ Donation in India 25.3 Brain Death 25.3.1 Definition 25.3.2 Pathophysiology of Brain Death [5], (Fig. 25.4) 25.3.3 Cardiovascular Changes 25.3.4 Pulmonary Changes 25.3.5 Endocrine, Metabolic, and Stress Response 25.3.6 Diagnosis of Brain Death 25.3.6.1 Apnea Test [6] 25.3.6.2 Ancillary Tests 25.3.7 Clinical Observations Compatible with the Diagnosis of Brain Death 25.3.8 Certification of Brain Death 25.4 Care of the Psychological Issues for Organ Donor Family and Treating Staffs 25.5 Conclusion Appendix References 26: Donation After Circulatory Death 26.1 Definition of Death 26.2 Ethical and Legal Issues in Donation After Cardiac Death (DCD) [8–13] 26.3 Process of DCD [15, 16] 26.4 Acceptable Time Limits in DCD 26.5 Ischaemia Reperfusion Injury (IRI) and Organ Preservation After DCD [15, 17, 19–24] 26.6 Machine Perfusion (MP) [19–24] 26.7 Functional Assessment of Organs [21] 26.8 Classification of Perfusion Techniques Based on Preservation Temperature [22] 26.9 Hypothermic Machine Perfusion (HMP) (0–12 °C) 26.10 Midthermic Machine Perfusion (13–24 °C) 26.11 Subnormothermic Machine Perfusion (25–34 °C) 26.12 Normothermic Machine Perfusion (35–38 °C) [22–24] 26.13 Normothermic Regional Perfusion (NRP) [23] 26.14 International DCD Programmes [7] 26.15 Lessons from UK Success Story in Overcoming Ethical, Legal and Professional Challenges [25, 26] 26.16 DCD in India [4] 26.17 Outcomes From DCD [9] 26.18 Future Trends and Directions for DCD [9, 19, 24, 25] Annexure: Major Ethical, Legal and Professional Publications on Deceased Organ Donation, United Kingdom [26] References 27: Management of Deceased Donor for Organ Donation 27.1 Introduction 27.2 Pathophysiological Changes Due to Brain Death 27.3 Approach to a Patient with Brain Death 27.4 General Care and Monitoring 27.5 Specific Management 27.6 Cardiovascular Support 27.6.1 Hypotension 27.6.1.1 Fluid 27.6.1.2 Monitoring 27.6.2 Hypertension 27.6.3 Arrythmias 27.7 Respiratory Care and Ventilatory Support 27.8 Acid-Base Balance 27.9 Renal Support 27.10 Endocrine Dysfunction 27.10.1 Central Diabetes Insipidus (CDI) 27.10.2 Hyperglycaemia 27.10.3 Thyroid Dysfunction 27.10.4 Cortisol Replacement Is Must. It Is Vital to Administer It as It 27.11 Temperature Regulation 27.12 Coagulation System 27.13 Infectious Disease Protection 27.14 Management of Nutrition 27.15 Ischaemia-Reperfusion Injury 27.16 Summary References 28: Normothermic Machine Perfusion 28.1 Introduction 28.2 Evolution of NMP 28.3 Organ Preservation (Table 28.2) 28.3.1 Static 28.3.2 Dynamic 28.3.3 Hypothermic Machine Perfusion (HMP) 28.3.4 Subnormothermic Machine Perfusion (SMP) 28.3.5 Normothermic Machine Perfusion (NMP) 28.4 Machine 28.5 Patho-Physiology During Preservation 28.6 Human Trials 28.7 COPE Trial (Consortium for Organ Preservation in Europe) 28.8 Parameters Assessed for Viability of Organ 28.9 Conclusion References 29: Role of ECMO in Liver Transplant 29.1 Introduction 29.2 ECMO Overview 29.3 ECMO Components [4] 29.4 Functions 29.5 ECMO Configurations: Fig. 29.4 29.5.1 Venoarterial ECMO (VA ECMO) 29.5.2 Venovenous ECMO (VV ECMO) 29.5.3 Management of Patient on ECMO 29.5.4 Complications 29.5.5 ECMO in Liver Transplantation 29.5.5.1 In Donors 29.5.5.2 In Recipients 29.6 ECMO for Transplant Donors 29.7 Brain Dead ECMO Patient as Potential Donor 29.7.1 Declaring Brain Death on ECMO [7–10] Can Be Considered Under the Following 29.8 Prerequisites for Testing for Brain Death 29.8.1 Establish Irreversible and Proximate Cause of Death 29.8.2 Correct Any Severe Electrolyte, Acid/Base, and Endocrine Disturbance 29.8.2.1 Neurological Examination 29.8.2.2 Apnoea Testing on ECMO: Fig. 29.5 29.8.2.3 Ancillary Tests 29.8.3 Role of ECMO in Deceased Donor Management 29.8.4 Donation After Cardiac Death (DCD) [14] 29.8.5 Challenges and Ethical Issues of EDCD [20] 29.8.6 Logistic, Economic, and Social Questions 29.8.7 Challenges in the Use of ECMO for Organ Donation Specific to India 29.8.8 ECMO in Liver Transplant Recipients: Who Would Benefit? 29.8.9 Acute Liver Failure 29.8.10 ECMO in Hepatopulmonary Syndrome 29.8.11 Perioperative ECMO 29.8.12 In Summary, When Should ECMO Be Offered for the CLD Patient Awaiting Liver Transplantation? [36, 37] 29.9 Conclusion References Part V: Acute Liver Failure 30: Critical Care Management of Acute Liver Failure 30.1 Introduction 30.1.1 Definition and Classification 30.2 Intracranial Hypertension (ICH), Hepatic Encephalopathy in ALF and Management 30.2.1 ICP Monitoring 30.2.2 Methods of ICP Monitoring 30.2.3 Therapeutic Interventions 30.2.3.1 General Supportive Strategies 30.2.4 Specific Strategies 30.2.4.1 Strategies to Reduce Hyperammonemia 30.2.5 Prophylactic Strategies 30.3 Specific Strategies to Reduce Cerebral Edema and ICH 30.4 Hemodynamic Derangement in ALF and Management 30.5 Nutritional and Metabolic Support in ALF 30.6 Respiratory Derangement in ALF and Management 30.7 Renal Derangement in ALF and Management 30.7.1 Renal Replacement Therapy 30.8 Hemostasis in ALF and Management 30.9 Infection and SIRS in ALF 30.9.1 Biomarkers 30.9.2 Prognosis and Liver Transplantation 30.10 Liver Support Devices in Acute Liver Failure [149] 30.11 Artificial Liver Support Devices (Non-cell Based) 30.12 Bio-Artificial Liver Support Devices (Cell-Based) References 31: Assessment for Transplanting Acute Liver Failure Patient 31.1 Introduction 31.2 Assessing Patients with ALF for Liver Transplantation 31.2.1 Assessing the Need for Transplant 31.2.2 Assessing Various Organ Systems 31.2.2.1 Central Nervous System 31.2.2.2 Cardiovascular System 31.2.2.3 Respiratory System 31.2.2.4 Renal System and Acid-Base, Fluid, Electrolyte Balance 31.2.2.5 Coagulation System 31.2.2.6 Other Considerations 31.2.3 Assessment for Presence of Contraindications to LT 31.3 Conclusion References 32: Bridging Therapies in Acute and Acute on Chronic Liver Failure 32.1 Introduction 32.2 Bridging Therapies 32.3 Therapeutic Plasma Exchange (TPE) 32.4 Liver Support System/Assist Devices 32.5 Molecular Adsorbent Recirculating/Recycling System 32.6 Fractionated Plasma Separation and Adsorption (Prometheus) 32.7 Single-Pass Albumin Dialysis 32.8 Extracorporeal Liver Assist Device 32.9 Experimental Regenerative and Cell-based Therapies 32.10 Bone Marrow-derived Stem Cells (In Vivo) 32.11 Hepatocyte Transplantation 32.12 Mesenchymal Stem Cell (MSC) Therapy 32.13 Role in ALF 32.14 Role in ACLF 32.15 Conclusion References 33: Anaesthetic Management of Acute Liver Failure for Liver Transplant 33.1 Background 33.2 Specific Concerns 33.3 Central Nervous System 33.4 Cardiovascular System 33.5 Coagulation 33.6 Renal Function 33.7 Too Sick To Be Considered for Liver Transplant 33.8 Shifting from ICU to Operating Room 33.9 Anaesthetic Management 33.10 Vascular Access 33.11 Hemodynamic Monitoring and Management 33.12 Neurologic Monitoring and Management 33.13 ICP Monitoring 33.14 Strategies to Reduce Intracranial Pressure 33.15 Pre-emptive Hepatectomy 33.16 Venovenous Bypass (VVB) and IVC Clamping 33.17 Managing the Coagulopathy 33.18 Metabolic Derangement 33.19 Renal Function Management 33.20 Use of Intraoperative CRRT 33.21 Postoperative Management References Part VI: Paediatric Liver Transplant 34: Anesthetic Issues in the Management of Pediatric Liver Transplantation 34.1 Introduction 34.2 Indications 34.3 Basis for Allocation 34.4 Timing of Transplantation 34.5 Pathophysiological Changes, Pre-operative Concerns, and Anesthetic Implications 34.5.1 Pulmonary 34.5.2 Cardiovascular 34.5.3 Central Nervous System 34.5.4 Renal 34.5.5 Gastrointestinal 34.6 Pre-operative Workup 34.7 Pre-operative Medication and Theater Preparation 34.8 Intraoperative Management 34.8.1 Induction 34.8.2 Intravenous (IV) and Intraarterial (IA) Access 34.8.3 Maintenance of Anesthesia 34.8.4 Temperature Management 34.8.5 Metabolic Management 34.8.6 Hemodynamic Management 34.8.7 Hematological Management 34.9 Stages of Liver Transplantation and the Specific Anesthetic Considerations 34.9.1 Dissection Phase- (Pre-hepatic Stage) 34.9.2 Anhepatic Phase 34.9.3 Neohepatic Phase 34.9.4 Elective Ventilation Vs. on Table Extubation 34.9.5 Early Post-operative Course 34.10 Pediatric Liver Transplantation: Special Circumstances 34.10.1 Acute Liver Failure 34.10.1.1 Management of PAL 34.10.2 Primary Hyper Oxaluria 34.10.3 Maple Syrup Urine Disease (MSUD) 34.11 Conclusion References 35: Challenges in Pediatric Liver Transplant 35.1 Introduction 35.2 Journey till the Transplant 35.3 Challenges in Pediatric Liver Transplant References 36: Intensive Care Issues in Post-operative Pediatric Liver Transplantation 36.1 Introduction 36.2 General Principles 36.3 Post-op Ventilation and Oxygenation 36.4 Fluids and Hemodynamics 36.5 Electrolytes and Metabolic Issues 36.6 Pulmonary Issues 36.7 Post-operative Hematological Issues: Bleeding and Coagulopathy 36.8 Gastrointestinal (GI) Concerns 36.9 Neurological Issues 36.10 Acute Kidney Injury (AKI) 36.11 Immunosuppression 36.12 Infections 36.13 Nutrition 36.14 Early Post-operative Complications Specific to Liver Graft 36.14.1 Primary Graft Failure 36.14.2 Size Discrepancy of Graft 36.14.3 Rejection 36.14.4 Vascular Issues 36.14.5 Biliary Issues 36.15 Conclusion References Part VII: Post-operative Issues 37: Fast Tracking in Liver Transplantation 37.1 Introduction 37.2 Definition and Evolution of Fast Tracking in LT 37.3 To Fast Track or Not? That’s the Question 37.3.1 Be Careful Before You Fast Track 37.3.2 Benefits of the Fast Track Approach 37.4 Anesthesia For Fast Tracking 37.5 Fast Tracking in the LDLT Setting 37.6 Criteria For Fast Tracking 37.7 Future Prospects References 38: Early Post-operative Care of Liver Transplant Recipient 38.1 Introduction 38.2 General Considerations 38.3 Cardiovascular and Hemodynamics 38.4 Respiratory System 38.5 Renal and Electrolyte Balance 38.6 Graft Function Assessment 38.7 Neurological Management 38.8 Pain Management 38.9 Infection Prophylaxis 38.10 Nutrition Management 38.11 Physiotherapy 38.12 Psychosocial Management 38.13 Conclusion References 39: Assessment of Early Graft Function and Management of Early Graft Failure 39.1 Incidence, Predictors, and Outcome of PGD 39.2 Assessment of Early Graft Function 39.3 Scoring Systems for Assessment of Graft Function Post-LT 39.4 Management of a Failing Graft 39.4.1 Deteriorating Recipient Physiology in PGD 39.4.2 General Principles of Management 39.4.3 Meticulous Surgical Care 39.4.4 ICU Management 39.5 General Supportive Care 39.5.1 Neurological Support 39.5.2 Mechanical Ventilation 39.5.3 Cardiovascular Support 39.5.4 Renal Support 39.5.5 Infection Prevention and Control 39.5.6 Nutritional Support 39.5.7 Immunosuppression 39.6 Specific Interventions 39.6.1 Use of N-Acetyl Cysteine 39.6.2 Role of Plasma Exchange in Graft Failure 39.6.3 Other Artificial Liver Support Systems in PGD 39.7 Use of Prostaglandins 39.8 Other Experimental Strategies References 40: Postoperative Renal Dysfunction in Recipient 40.1 Objective 40.2 Preamble 40.3 Definition of AKI 40.3.1 RIFLE Criteria 40.3.2 Acute Kidney Injury Network (AKIN) Classification 40.3.3 KIDGO Revision of RIFLE and AKIN Criteria 40.4 Why Do We Need to Change the Conventional Diagnostic Criteria for AKI? 40.5 Assessment of Renal Function Before and After Liver Transplantation 40.6 Biomarkers of AKI 40.7 Burden of Renal Dysfunction After Liver Transplantation 40.8 Risk Factors for Postoperative Acute Kidney Injury After Orthotopic Liver Transplantat 40.8.1 Pre-transplantation Risk Factors 40.8.2 Hyponatremia 40.8.3 Hypoalbuminemia 40.8.4 Hyperbilirubinemia 40.8.5 Liver Disease Severity 40.9 Strategies to Reduce Pre-transplantation Risk Factors 40.9.1 Studies Evaluating the Effect of Terlipressin in HRS 40.9.2 Role of Nonpharmacological Therapies 40.9.3 Role of Simultaneous Liver and Kidney Transplant 40.10 Intraoperative Risk Factors 40.11 Strategies to Reduce Intraoperative Risk Factors 40.12 Postoperative Risk Factors