Organ Donation and Transplantation after Cardiac Death in China: Clinical practice

Preface
Contents
1: Legal, Moral, and Ethical Issues Related to Cardiac Death Donation
	1.1	 Categories and Features of DCD
	1.2	 The Historical Background and Global Trends of DCD Development
	1.3	 WHO Legal of Organ Donation
	1.4	 Ethical Supervision in the DCD Donation Process
	1.5	 Ethical Considerations on the Development of DCD
		1.5.1	 Family-Based Ethics Has Become an Obstacle for Individual’s Donation
		1.5.2	 The Emotional Necessity of Family Ethics Have Weakened Individual Willingness of Donation
		1.5.3	 DCD’s Technical Risks Make Donation Hover
	1.6	 The Ethical Principles Adopted by DCD at Present
		1.6.1	 Principle of Informed Consent
		1.6.2	 No Harm Principle
		1.6.3	 Principle of Donation After Death
	1.7	 Strategy of Sustainable Development for DCD
		1.7.1	 Establish a Fair, Equitable, and Open Organ Allocation and Sharing Mechanism
		1.7.2	 Give Reasonable Compensation to Donors
		1.7.3	 Improvement of DCD Utilization and Organ Quality
	1.8	 Conclusion
	References
2: Current Situation of Organ Donation After Cardiac Death in China
	2.1	 Preclinical Research on Non-Heart-Beating Donor
	2.2	 Current Situation of DCD Organ Transplantation Out of China
	2.3	 Discussion of Death Criteria and the Origination of Brain Death
	2.4	 Impact of Brain Death Criterion on Transplant Development
	2.5	 Classification of DCD Donation
	2.6	 Clinical Application and Prognosis of DCD Organ Transplantation
	2.7	 The Development of Organ Donation After the Death of Domestic Citizens in China
	References
3: Cardiac Death Donor Evaluation and Management
	3.1	 The Evaluation of Cardiac Death Donor
		3.1.1	 The Classification of DCD
	3.2	 Cardiac Death Prediction
		3.2.1	 The UW Criteria
		3.2.2	 The UNOS Criteria
		3.2.3	 The DCD-N Score
		3.2.4	 The C-DCD-Nomogram
	3.3	 Prediction of Progress to Brain Death
		3.3.1	 Neurological Examination
		3.3.2	 Neuroimaging
			3.3.2.1	 Swirl Sign [12]
			3.3.2.2	 Cisterna Ambiens [13]
			3.3.2.3	 Intraventricular Hemorrhage [14]
			3.3.2.4	 Brain Herniation [15]
		3.3.3	 Spontaneous Respiratory Arrest Prediction
	3.4	 Donor Management in ICU
		3.4.1	 Goal-Directed Protocols
		3.4.2	 Ventilation
		3.4.3	 Hemodynamic management
			3.4.3.1	 Infusion/Fluid
			3.4.3.2	 Vasoactive Drugs
		3.4.4	 Endocrine Management
			3.4.4.1	 Vasopressin Deficiency
			3.4.4.2	 Hypothyroidism
			3.4.4.3	 Corticosteroid
		3.4.5	 Nutrition and Glycemia
		3.4.6	 Temperature Management
		3.4.7	 Transfusion
		3.4.8	 Infection Management
	References
4: Organ Procurement, Quality Evaluation, and Perfusion
	4.1	 Organ Procurement
		4.1.1	 Liver Acquisition Technology
			4.1.1.1	 Rapid DCD Donor Organ Procurement Technology
			4.1.1.2	 Collect DCD in Whole to Donate Liver, Pancreas, Spleen, Duodenum, Part of Jejunum, and Bilateral Kidneys
			4.1.1.3	 Precautions in the Process of Donating Liver
		4.1.2	 Kidney Acquisition Technology
			4.1.2.1	 Preoperative Preparation
			4.1.2.2	 Entire Kidney Removal Method (Fig. 4.1)
		4.1.3	 Heart and Lung Acquisition Technology
			4.1.3.1	 Acquisition Technology of Donor Heart
			4.1.3.2	 Combined Acquisition Technology of Donor Heart and Lung
			4.1.3.3	 Acquisition Technology of Donor Lung
		4.1.4	 Special Organ Acquisition Technology
			4.1.4.1	 In Vivo Split Liver Transplantation Technology
			4.1.4.2	 Technical Points of In Vivo Split Liver Transplantation
		4.1.5	 Kidney Acquisition in Children
		4.1.6	 Multiple Organ Procurement Technology
			4.1.6.1	 Multiple Organ Transplantation
			4.1.6.2	 Donor Surgery
			4.1.6.3	 Recipient Surgery
			4.1.6.4	 Treatment after Transplantation and Diagnosis and Treatment of Complications
	4.2	 Quality Evaluation
		4.2.1	 Purpose of Evaluation
		4.2.2	 Basic Evaluation
		4.2.3	 Special Evaluation
		4.2.4	 Evaluation of Organ Function
			4.2.4.1	 Evaluation and Selection of Renal Function
			4.2.4.2	 Evaluation and Selection of Hepatic Function
			4.2.4.3	 Evaluation and Selection of Heart Function
			4.2.4.4	 Evaluation and Selection of Lung Function
			4.2.4.5	 Evaluation and Selection of Pancreatic Function
			4.2.4.6	 Evaluation and Selection of Small Bowel Function
	4.3	 Organ Perfusion in Donation After Cardiac Death
		4.3.1	 The History of Machine Perfusion and Preservation
		4.3.2	 Machine Perfusion
			4.3.2.1	 Different Types of Machine Perfusion
			4.3.2.2	 The Advantages of Machine Perfusion
		4.3.3	 Machine Perfusion of Major Organs
			4.3.3.1	 Machine Perfusion of Kidney
			4.3.3.2	 Machine Perfusion of Liver
			4.3.3.3	 Machine Perfusion of Heart/ Lung
			4.3.3.4	 Machine Perfusion of Pancreases
	References
5: Liver Transplantation from Cardiac Death Donors
	5.1	 Indications and Timing of Liver Transplantation
		5.1.1	 Acute Liver Failure (ALF)
		5.1.2	 Chronic Cirrhosis
		5.1.3	 Malignant Liver Disease
		5.1.4	 Congenital Metabolic Disease of the Liver
	5.2	 Preoperative Evaluation and Preparation of the Recipient
		5.2.1	 Preoperative Evaluation
			5.2.1.1	 Surgical Indications and Timing Evaluation
			5.2.1.2	 Evaluation of Surgical Tolerance and Contraindications
				Cardiac Function
				Respiratory System
				Renal Function
				Infectious Diseases
				Coagulation Function
				Nutritional Status
				Evaluation of Primary Disease
			5.2.1.3	 Surgical Feasibility and Imaging Assessment
				Reevaluation of Primary Disease in Recipients
				Imaging Assessment of Recipients
			5.2.1.4	 Recipient Compatibility Assessment
				General Evaluation
				Evaluation of Immune Compatibility
				Virological Assessment
			5.2.1.5	 Treatment of Liver Transplantation Recipients During Waiting Period
				Treatment of Bleeding from Gastric Fundus and Esophageal Varices
				Correct Abdominal and Circulatory Disorders
				Protect Renal Function
				Prevention and Treatment of Hepatic Encephalopathy
				Improve Coagulation Function
			5.2.1.6	 Treatment of Patients with Liver Malignant Tumor Waiting for Liver Transplantation
			5.2.1.7	 Antiviral Therapy Before Liver Transplantation
			5.2.1.8	 Preparation Before Liver Transplantation
		5.2.2	 Donor Evaluation and Selection
			5.2.2.1	 Hot Ischemia Time
			5.2.2.2	 Donor Selection
				Donor Screening
				Marginal Donor Liver
				Contraindication of DCD Donor Liver
		5.2.3	 Liver Lavage, Preservation, and Repair
	5.3	 Liver Transplantation
		5.3.1	 Classic Orthotopic Whole Liver Transplantation
			5.3.1.1	 Resection of Diseased Liver
			5.3.1.2	 Anastomosis of Hepatic Superior and Inferior Vena Cava
			5.3.1.3	 Subhepatic Inferior Vena Cava Anastomosis
			5.3.1.4	 Portal Vein Anastomosis
			5.3.1.5	 Restore Blood Supply of Transplanted Liver
			5.3.1.6	 Hepatic Artery Anastomosis
			5.3.1.7	 Reconstruction of Bile Duct
			5.3.1.8	 Place the Drainage Tube
		5.3.2	 Piggyback Orthotopic Liver Transplantation
		5.3.3	 Reduced Volume Liver Transplantation
		5.3.4	 Split Liver Transplantation (SLT)
	5.4	 Postoperative Management of Liver Transplantation
		5.4.1	 ICU Treatment After Liver Transplantation
			5.4.1.1	 Immediate Treatment After ICU Admission
			5.4.1.2	 Evaluation and Monitoring of Organ Function
			5.4.1.3	 Early Evaluation of Graft Function
			5.4.1.4	 Prevention of Complications in ICU
				Coagulation Function
				Respiratory System
				Circulation System
				Renal Function
				Gastroenteric Function
				Neuropsychiatric System
		5.4.2	 Routine Management After Liver Transplantation
			5.4.2.1	 Monitoring of Transplanted Liver Function
				Clinical Observation
				Laboratory Inspection
				Imaging Examination
				Liver Biopsy
			5.4.2.2	 Postoperative Drug Therapy
				Selection of Immunosuppressive Regimen
				Use of Anti-infective Drugs
	5.5	 Management of Postoperative Complications After Liver Transplantation
		5.5.1	 Primary Liver Nonfunction (PNF) and Early Liver Insufficiency (EAD)
			5.5.1.1	 Risk Factors of PNF and EAD
			5.5.1.2	 Prevention and Treatment of PNF and EAD
		5.5.2	 Infection After Liver Transplantation
			5.5.2.1	 Risk Factors for Infection
			5.5.2.2	 Specific Measures for Postoperative Infection Management Include
		5.5.3	 Postoperative Abdominal Hemorrhage
			5.5.3.1	 The Causes of Abdominal Hemorrhage Mainly Include Two Aspects
			5.5.3.2	 The Treatment of Abdominal Hemorrhage After Liver Transplantation Should Focus on Prevention
		5.5.4	 Bile Duct Complications After Liver Transplantation
			5.5.4.1	 Pathogenesis of Biliary Disease
			5.5.4.2	 Diagnosis of Biliary Complications
			5.5.4.3	 Prevention and Treatment of Bile Duct Complications
		5.5.5	 Rejection After Liver Transplantation
			5.5.5.1	 Types of Rejection
			5.5.5.2	 Treatment of Rejection After Liver Transplantation
		5.5.6	 Vascular Complications After Liver Transplantation
			5.5.6.1	 Arterial Complications
			5.5.6.2	 Venous Complications
	References
6: Kidney Transplantation from Cardiac Death Donors
	6.1	 Current Situation and Trends of Kidney Transplantation from Cardiac Death Donors
	6.2	 Classification of Donation After Cardiac Death
	6.3	 Donation Process of Cardiac Death Donors
	6.4	 Early Graft Function of DCD Kidney Transplantation
	6.5	 Graft and Patient Survival of DCD Kidney Transplantation
	6.6	 Graft Function of Recipients of DCD Kidney Transplantation
	6.7	 Risk Factors Associated with Outcome of DCD Kidney Transplantation
	6.8	 Selection of DCD Kidneys
	6.9	 Pediatric DCD Kidney Transplantation
	6.10	 Postoperative Management of DCD Kidney Transplantation
		6.10.1	 Peri-Operative Fluid Management
		6.10.2	 Post-Transplant Monitoring
		6.10.3	 Immunosuppressive Therapy Protocol
	References
7: Lung Transplantation from Cardiac Death Donors
	7.1	 Overall Introduction of Lung Transplantation in China
	7.2	 Donor Selection Criteria
	7.3	 Management of Deceased Cardiac Death Donors
	7.4	 Survival Status of Lung Transplant Recipients in China
	7.5	 DCD and DBD Lungs in Transplantation
	7.6	 Lung Transplantation in China, Past and Future
	References
8: Pancreas and Islet Transplantation from Cardiac Death Donors
	8.1	 Pancreas Transplantation
		8.1.1	 Indications and Contraindications [5–7]
			8.1.1.1	 Indications
			8.1.1.2	 Contraindications
		8.1.2	 Surgical Technique
		8.1.3	 Postoperative Management
		8.1.4	 Immunosuppressant
		8.1.5	 Complications
			8.1.5.1	 Rejection
				Hyperacute Rejection [7]
				Acute Rejection [12–14]
				Chronic Rejection [15–16]
			8.1.5.2	 Intraperitoneal Bleeding [15, 17]
			8.1.5.3	 Thrombosis in Pancreas Allograft [15, 18]
			8.1.5.4	 Pancreatitis in Pancreas Allograft [15, 19]
			8.1.5.5	 Pancreatic Leakage and Pancreatic Fistula [15, 17, 20]
	8.2	 Islet Transplantation
		8.2.1	 Indications and Contraindications
		8.2.2	 Quality Assessment of Donor Pancreas and Islets
			8.2.2.1	 Selected Criteria of Donor Pancreas
			8.2.2.2	 Assessment of Donor Islet
		8.2.3	 Donor Pancreatic Procurement and Islet Preparation
		8.2.4	 Procedures for Islet Transplantation
		8.2.5	 Postoperative Treatment and Immunosuppressive Regimens
		8.2.6	 Complications
		8.2.7	 Islet Auto Transplantation
	References
9: Multiple Organ Transplantation from Cardiac Death Donors
	9.1	 Nomenclature
	9.2	 Indications and Contraindications
		9.2.1	 Indications
		9.2.2	 Contraindications
	9.3	 Preoperative Assessment
	9.4	 Donor Operation and Recipient Surgery
		9.4.1	 Donor Operation
		9.4.2	 Recipient Surgery
	9.5	 Postoperative Care
	9.6	 Post-Transplantation Complications
		9.6.1	 Early Post-Transplantation Complications
		9.6.2	 Immunosuppression and Rejection
		9.6.3	 Infection
	9.7	 Outcomes Following Transplantation
	References
10: Immunosuppressive Strategies in Transplantation Using Cardiac Death Donors
	10.1	 Introduction
	10.2	 Mechanisms of Rejection in Transplantation
		10.2.1	 Adaptive Immune Cells
			10.2.1.1	 T Cells
				T Cell Depletion
				Blocking T Cell Activation and Function
				Increasing Regulatory T Cells
			10.2.1.2	 B Cells
		10.2.2	 Innate Immune Cells
			10.2.2.1	 Macrophages/Monocytes
			10.2.2.2	 Dendritic Cells (DCs)
			10.2.2.3	 Natural Killer (NK) Cells
	10.3	 The History of the Development of Immunosuppressive Drugs
		10.3.1	 Azathioprine
		10.3.2	 Ciclosporin A (CsA)
		10.3.3	 Tacrolimus (FK506)
	10.4	 Comparison of the Outcomes for Transplantation Between DBD and DCD
	10.5	 Updates on Immunosuppressive Protocols in DCD Transplantation
	10.6	 Conclusion
	References
11: Ischemia and Reperfusion Injury in Organ Transplantation from Cardiac Death Donors
	11.1	 Overview
		11.1.1	 Definition of Ischemia-Reperfusion Injury (IRI)
		11.1.2	 Impact of IRI on the Graft and IRI Features in DCD Donors
			11.1.2.1	 Impact of IRI on Renal Transplantation
			11.1.2.2	 Impact of IRI on Liver Transplantation
			11.1.2.3	 Impact of IRI on Lung Transplantation
	11.2	 Pathophysiological Mechanisms of IRI
		11.2.1	 Damage by Reactive Oxygen Species
		11.2.2	 Calcium Overload
		11.2.3	 Impact of Leukocyte
	11.3	 Molecular Mechanisms Involved in IRI Regulation
		11.3.1	 Toll-Like Receptors Pathways
		11.3.2	 Heat Shock Protein (HSP) Pathway
		11.3.3	 Hypoxia-Inducible Factor (HIF) Pathway
		11.3.4	 Autophagy and IRI
		11.3.5	 Ferroptosis and IRI
	11.4	 Treatment of IRI
		11.4.1	 Clinical Guidelines for the Treatment of Donor Organs
			11.4.1.1	 Optimize the Evaluation and Maintenance of Donors in ICU
			11.4.1.2	 Shorten the Organ Acquisition and Transportation Time, Optimize the Surgical Procedure and Organ Preservation Method
			11.4.1.3	 Postoperative Patient Management
		11.4.2	 Preclinical Research
			11.4.2.1	 Ischemic Preconditioning and IRI
			11.4.2.2	 Protective Drugs of IRI
	11.5	 New Methods to Reduce IRI
		11.5.1	 Stem Cell Therapy and IRI
		11.5.2	 Exosomes and IRI
		11.5.3	 Autophagy Modulators and IRI
	References
12: Imaging Related to Transplantation from Cardiac Death Donors
	12.1	 Liver Transplantation
		12.1.1	 Vascular Complications
			12.1.1.1	 Hepatic Artery
			12.1.1.2	 Portal Vein
			12.1.1.3	 Inferior Vena Cava and Hepatic Vein
		12.1.2	 Biliary Complications
			12.1.2.1	 Biliary Strictures
			12.1.2.2	 Biliary Obstruction
			12.1.2.3	 Biliary Stones
			12.1.2.4	 Biliary Leak
			12.1.2.5	 Biloma
		12.1.3	 Parenchymal Complications
			12.1.3.1	 Hepatic Infarction
			12.1.3.2	 Intrahepatic Abscess
			12.1.3.3	 Fatty Liver or Recurrent Liver Cirrhosis
		12.1.4	 Hepatocellular Cancer
		12.1.5	 Perihepatic Fluid Collections
		12.1.6	 Posttransplantation Lymphoproliferative Disorder
		12.1.7	 Rejection
	12.2	 Renal Transplantation
		12.2.1	 The Normal Renal Allograft
		12.2.2	 Vascular Complications
			12.2.2.1	 Renal Artery Thrombosis (RAT)
			12.2.2.2	 Transplant Renal Artery Stenosis
			12.2.2.3	 Renal Vein Thrombosis
			12.2.2.4	 Arteriovenous Fistula
			12.2.2.5	 Transplanted Renal Artery Pseudoaneurysm
		12.2.3	 Renal Allograft Parenchymal Complications
		12.2.4	 Perinephric Fluid Collections
			12.2.4.1	 Perinephric Hematoma
			12.2.4.2	 Urinoma
			12.2.4.3	 Perinephric Abscess
			12.2.4.4	 Lymphocele
		12.2.5	 Obstructive Urologic Complications
		12.2.6	 Infectious Complications: Polyomavirus Nephropathy
	12.3	 Conclusions
	References
13: Pathological Evaluation of DCD Donor Organs
	13.1	 Pathological Evaluation of DCD Donor Liver
		13.1.1	 Significance of DCD Liver Biopsy
		13.1.2	 Time Points for Biopsy and Technical Considerations
		13.1.3	 Evaluation of Procurement/Harvest Biopsy
			13.1.3.1	 Steatosis
			13.1.3.2	 Tumors
			13.1.3.3	 Necrosis, Inflammation, and Fibrosis
			13.1.3.4	 Other Pre-existing Changes
		13.1.4	 Evaluation of Time-Zero Biopsy
	13.2	 Evaluation of DCD Donor Kidney
		13.2.1	 Significance of DCD Kidney Biopsy
		13.2.2	 Time Points for Biopsy and Technical Considerations
		13.2.3	 Evaluation of Procurement/Harvest Biopsy
			13.2.3.1	 Percentage of Glomerular Sclerosis
			13.2.3.2	 Arterial and Arteriolar Lesions
			13.2.3.3	 Acute and Chronic Lesions of Tubules and Interstitium
			13.2.3.4	 Neoplasm of Donor Kidney
		13.2.4	 Evaluation of zero-Time Biopsy
	References
14: Further Development of Organ Transplantation from Cardiac Death Donors in China
	14.1	 Future Technique Development of DCD
		14.1.1	 Further Development of Reducing Organ Injury and Improve Organ Function After DCD
			14.1.1.1	 Prior to Organ Recovery: In Situ Normothermic Regional Perfusion
			14.1.1.2	 After Organ Recovery: Ex-Situ Machine Perfusion
		14.1.2	 Further Development of Increasing the Number of Usable DCD Organs
	14.2	 The Improvement of the Awareness of DCD
	14.3	 Legislation of Practical Guiding Significance in Whole Process of DCD
	References