Oxford Textbook of Transplant Anaesthesia and Critical Care Oxford Textbooks in Anaesthesia Oxford Textbook of Anaesthesia for the Elderly Patient Edited by Chris Dodds, Chandra M. Kumar, and Bernadette Th Veering Oxford Textbook of Anaesthesia for Oral and Maxillofacial Surgery Edited by Ian Shaw, Chandra M. Kumar, and Chris Dodds Principles and Practice of Regional Anaesthesia, Fourth Edition Edited by Graeme McLeod, Colin McCartney, and Tony Wildsmith Oxford Textbook of Cardiothoracic Anaesthesia Edited by R. Peter Alston, Paul S. Myles, and Marco Ranucci Oxford Textbook of Transplant Anaesthesia and Critical Care Edited by Ernesto A. Pretto, Jr., Gianni Biancofiore, Andre De Wolf, John R. Klinck, Claus Niemann, Andrew Watts, and Peter D. Slinger Free personal online access for 12 months Individual purchasers of this book are also entitled to free personal access to the online edition for 12 months on Oxford Medicine Online () Please refer to the access token card for instructions on token redemption and access Online ancillary materials, where available, are noted at the end of the respective chapters in this book Additionally, Oxford Medicine Online allows you to print, save, cite, email, and share content; download high-resolution figures as Microsoft PowerPoint slides; save often-used books, chapters, or searches; annotate; and quickly jump to other chapters or related material on a mobile-optimized platform We encourage you to take advantage of these features If you are interested in ongoing access after the 12-month gift period, please consider an individual subscription or consult with your librarian Oxford Textbook of Transplant Anaesthesia and Critical Care Editor-in-Chief Ernesto A. Pretto, Jr Editors Gianni Biancofiore Andre De Wolf John R. Klinck Claus Niemann Andrew Watts Contributing Editor Peter D. Slinger 1 Great Clarendon Street, Oxford, OX 2 6DP, United Kingdom Oxford University Press is a department of the University of Oxford It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Oxford University Press 2015 The moral rights of the authorshave been asserted First Edition Published in 2015 Impression: 1 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by licence or under terms agreed with the appropriate reprographics rights organization Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2014948994 ISBN 978–0–19–965142–9 Printed in China by Asia Pacific Offset Ltd Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations The authors and the publishers not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breast-feeding Links to third party websites are provided by Oxford in good faith and for information only Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work Foreword Organ transplantation began with kidney transplantation in the early 1950s and expanded to heart, lung, liver, pancreas, multiviscera, and xenograft transplantation Its evolution over the past 50 years or so has been dramatic The experimental stage of organ transplantation (1960–1980) evolved into the developmental stage (1980–1990) and refinement stage (1991–present) with excellent clinical outcomes This evolution has been made possible by better understanding of the scientific basis of transplantation, which includes immunology and pathophysiology and continuously improving surgical technique and perioperative care It is noteworthy that the role of anaesthesiologists and intensivists has been vital in its progression, because organ transplantation is a medical field that requires a multidisciplinary approach by dedicated physicians and scientists of all medical fields I am extremely pleased to witness the publication of the Oxford Textbook of Transplant Anaesthesia and Critical Care edited by Drs Biancofiore, De Wolf, Klinck, Niemann, Pretto, Slinger, and Watts, who are my respected colleagues and experts in the transplantation field The major strength of this textbook can be found in its comprehensiveness and the inclusion of scientific bases It begins with the history of organ transplantation and includes ethics, organ donation, and perioperative management of all transplanted organs The molecular basis of organ transplantation should encourage further exploration in organ preservation, prevention of ischaemic injury, and modulation of rejection phenomena The book presents many ideas and concepts to guide the future direction of transplant anaesthesiology, critical care and research, a vital issue for further development of organ transplantation Organ transplantation, particularly the field of anaesthesiology and critical care medicine, was once believed to be a ‘black hole’—an amorphous unknown object with a huge mass absorbing all resources without a trace We now have a much better understanding of that black hole, and I believe that we are better equipped to explore the unknown universe with the guidance of this textbook As a long-time anaesthesiologist in the transplantation field, I sincerely appreciate all editors and contributors for their life-time dedication to organ transplantation Yoogoo Kang, MD Professor, Anesthesiology Director, Hepatic Transplantation Anesthesiology Thomas Jefferson University Preface So the LORD GOD caused a deep sleep to fall upon the man, and he slept; then He took one of his ribs and closed up the flesh at that place —Genesis 2:21 Organ transplantation is a relatively new medical science that has made it possible for patients with an irreversibly damaged organ, and little hope of long-term survival, to receive a replacement organ from another human-being, living or deceased This ancient idea, once also the purview of science-fiction novels, has become reality, and it is revolutionizing medical care by bringing renewed hope for healing to thousands of patients worldwide, every day The only limitation to a much wider application of this life-saving technology is the scarcity of suitable organs The successful and steady evolution of the field of clinical organ transplantation over the past 100 years or so is directly attributable to the multidisciplinary nature and scientific basis of transplant care In fact, only since 1995 during which time medical technology has made great strides forward have we seen marked improvements in long-term survival, including among recipients of the most complex transplant procedures In particular, advances in perioperative and critical care management of the transplant recipient have accounted to a great extent for these recent improvements in outcomes One of those seminal achievements was the initiation by a group of anaesthesiologists and intensive care physicians at the University of Pittsburgh of a multidisciplinary approach to liver transplantation The first gathering of this group in 1982 was called ‘Anesthesia and Perioperative Care in Liver Transplantation’, which later became the International Liver Transplantation Society (ILTS) In a letter dated August 1993 by Dr Thomas Starzl, a renowned American liver transplant pioneer, to Dr Peter Safar, a critical care medicine pioneer and founding Chairman of the Department of Anesthesiology and Critical Care Medicine at the University of Pittsburgh, who was then director of what is now known as the Safar Center for Resuscitation Research, Starzl wrote: . . I have always taken pains to point out how what we would be utterly impossible without the marvelous collaboration of our unselfish colleagues who work in the operating room and slave over these terribly sick patients afterwards In a much more professionally meaningful but less public way, we have promoted the interests of the anesthesia and ICU physicians by passing the leadership baton onto Kang et al., for the organization of the International Liver Transplantation Society that will be meeting for the second time this year in Canada Dr. Kang’s efforts and those of his intensive care colleagues were responsible for the birth of this very important organization . . . In the same vein, the American Society of Anesthesiologists (ASA) described the nature of anaesthesia practice for organ transplantation, and those anaesthesiologists and intensivists engaged in its delivery, in the following manner: The complexity of transplant surgeries requires the expertise and specialty of a transplant anesthesiologist who is an integral part of the transplant team Transplant anesthesiologists have an extensive background in critical care medicine, cardiac anesthesiology and/ or pediatric anesthesiology This type of anesthesiologist also provides consultation in both the preoperative and intraoperative stages of care This statement was a first step in the direction of defining the knowledge base, required training and experience, and scope of practice of the ‘transplant anaesthesiologist’ Likewise, a recent ‘landmark’ decision by the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) (the principal government-mandated agency overseeing organ procurement and sharing in the US), in partnership with the ASA Committee on Transplantation, has promulgated guidelines for the qualifications and clinical responsibilities of the director of liver transplant anaesthesia programmes, as follows: The director of liver transplant anesthesia should have one of the following: Fellowship training in Critical Care Medicine, Cardiac Anesthesiology, or a Liver Transplant Fellowship, that includes the peri-operative care of at least 10 liver transplant recipients Experience in the peri-operative care of at least 20 liver transplant recipients in the operating room, within the last 5 years Experience acquired during postgraduate residency training does not count for this purpose viii preface The director of liver transplant anesthesia has clinical responsibilities that include but are not limited to the following: ◆ Pre-operative assessment of transplant candidates ◆ Participation in candidate selection ◆ Intra-operative ◆ Post-operative management visits ◆ Participation on the Selection Committee ◆ Consultation pre-operatively with subspecialists as needed ◆ Participation in morbidity and mortality (M&M) conferences (UNOS Bylaws) These guidelines provide official recognition that expertly trained anaesthesiologists are critical to optimizing transplant care The UNOS bylaws endorse transplant anaesthesiologists’ active participation in medical decision-making in all facets of transplant care We believe these guidelines should not be limited to the care of liver transplant recipients alone but that the benefits of multidisciplinary care and specialized training in transplant anaesthesia will inevitably lead to improved care for all types of organ transplant recipients, as well as organ donors Other than pain management and critical care medicine, perhaps there is no other subspecialty of anaesthesiology where our involvement has been as important to improved outcomes and as valued by our professional counterparts Therefore the impetus for a book on ‘Transplant Anaesthesia and Critical Care’ derives from the same spirit of collaboration and collegiality that seeks to affirm the current trend towards greater specialization in transplant anaesthesia and critical care Specifically, this book attempts to define the normative body of scientific and clinical knowledge, skill, and training that is essential to the expertise of the anaesthesiologist involved in the care of the organ donor as well as the organ transplant recipient On behalf of the editors, the expectation is that the appearance of this book is timely, relevant, and true to the present state-ofthe-art and that it will bolster the continued development of the burgeoning field of transplant anaesthesia and critical care As you will see on initial perusal of the table of contents we have taken a holistic approach to the scope of practice of transplant anaesthesia In so doing we cover in depth many aspects of transplantation of the major organ systems Moreover, we have assembled a cadre of multidisciplinary transplant experts from several continents that present updated evidence-based information on various topics related to transplantation, including data on organ transplant practices in leading countries, as well as some of the ethical challenges facing the field of organ transplantation today We hope this book will be well received by the medical and scientific communities and that it will serve as the authoritative reference work in the field, thereby forming the basis for the design of curricula for teaching and training of medical students, anaesthesia residents, transplant anaesthesia fellows, nurse anaesthetists, and attending anaesthesiologists in transplant care Finally, we believe that the future of transplant anaesthesia relies heavily on discovery As such we hope this book will provide the reader with key insights into cellular mechanisms of ischaemia–reperfusion injury that will inspire transplant anaesthesiologists to engage in basic and clinical research, and in so doing contribute to the collective advancement of the science of transplantation Ernesto A. Pretto, Jr., MD, MPH Miami Transplant Institute Contents Abbreviations xiii Editors xix Contributors xxi SEC TION 1 Introduction History of organ transplantation John R. Klinck and Ernesto A. Pretto, Jr 2 The development of organ donation systems and regulatory bodies in the United States 13 Nikole Neidlinger, Sean Van Slyck, and Daniel M. Bruggebrew Organ donor allocation and transplant logistics: the European perspective 23 Gabriela A. Berlakovich and Thomas Soliman SEC TION 2 Introduction to transplant ethics Acquiring organs ethically: problems and prospects 33 Jamie Lindemann Nelson Organ allocation: a guide for the perplexed 43 Benjamin E. Hippen Ethical issues in transplant tourism and organ commercialism 53 Robin N. Fiore SEC TION 3 The organ donor Neurological determination of death and organ donation 61 Shariq S. Raza, Ali Salim, and Darren J. Malinoski Critical care of the organ donor 69 Matthew B. Bloom, Ali Salim, and Darren J. Malinoski Research in organ donors: future directions 77 Claus Niemann and Andrea Olmos SECTION 4 The scientific basis of organ transplantation 10 Organ resuscitation 87 Ernesto A. Pretto, Jr., Kyota Fukazawa, and Antonello Pileggi 11 Transplant immunology 99 Phillip Ruiz, Junichiro Sageshima, George Burke, Linda Chen, and Gaetano Ciancio 12 Xenotransplantation 111 Kazuhiko Yamada, Joseph Scalea, and Masayuki Tasaki SECTION 5 Kidney and kidney–pancreas 13 Indications, selection, and evaluation of the kidney transplant candidate 125 M Francesca Egidi and Giuseppe Segoloni 14 Kidney transplantation: perioperative cardiovascular risk and anaesthetic management 131 Livia Pompei, Maria Gabriella Costa, Mauricio Sainz-Barriga, George Burke, and Giorgio Della Rocca 15 Perioperative management of the kidney–pancreas and pancreas transplant recipient 141 Ugo Boggi, George Burke, and Kumar Belani 454 index heart–lung transplantation (Cont.) indications 315 intensive care 349 intubation 317 liver dysfunction 316 non-surgical bleeding 318–19 one-lung ventilation 317 postoperative management 319 pregnancy and 434–5 preoperative assessment 315–16 previous surgery 316 primary graft dysfunction 318 renal dysfunction 316 reperfusion 318 respiratory assessment 316 right ventricular dysfunction/ failure 318 surgical team 315 TOE 317 heart transplantation acute rejection 312, 343–4 anaesthesia induction 309–10 anaesthesia maintenance 310 anaesthetic management 307–11 antifibrinolytics 310–11 atrial fibrillation 311 awareness risk 309 cardiac allograft vasculopathy 312, 344, 360 cardiopulmonary exercise testing 307 children, see paediatric heart transplantation contraindications 309 denervated heart 341 dysrrhythmias 311, 340 endomyocardial biopsy 344 heart rate and rhythm 340 history of 6 immunosuppression 312, 342, 343 indications 307 infection risk 311, 342–3 inhaled nitric oxide 311 intensive care 339–4 intraoperative monitoring 309 logistics 27 long-term complications 312 malignancy risk 344 non-transplant surgery 424–5 organ allocation 27 organ donor management 307 pacing 311, 340 paediatrics, see paediatric heart transplantation physiology and pharmacology of transplanted heart 340–2 postoperative bleeding 311 postoperative management 311–12, 339–40 pregnancy and 434–5 preload and afterload 340 premedication 309 preoperative assessment 307–9 prostacyclin 311 prostaglandin E1 311 pulmonary hypertension 307, 309 right heart function 341–2 separation from cardiopulmonary bypass 311 survival 307 TOE 309 transition to ICU 339 transpulmonary gradient 308–9 ventricular assist device 342, 357 waiting list management 307 xenotransplantation 111 heparin 398 heparinase 397 hepatic encephalopathy 191, 213–14, 215, 244–6, 261, 262, 268 hepatitis B 183 hepatitis C 183, 184, 206 hepatocellular carcinoma cell salvage 409–10 epidemiology 183 indications and selection criteria for transplantation 201, 202 referral guidance for transplantation 207 hepatopulmonary syndrome 192–3, 227, 260, 270 hepatorenal syndrome 189, 260 high urgency requests 26 histamine 246 histidine–tryptophan–ketoglutarate solution 5 histocompatibility clinical laboratories 101 history of transplantation 3–10, 111, 353 HIV 15, 206 HLA antibodies 125, 300, 332, 357, 386–7 HLA class I/II molecules 99 HLA typing 101 HOPE Act 15 hormonal deficiencies, neurological death 71 hormone replacement therapy 73 hospital development 17–18 host versus graft response 100–1 HTK solution hydrocortisone 102 hydrothorax 189 hydroxyethyl starch 136, 254 hyperacute rejection 112 hyperkalaemia 194, 223, 292–3, 415 hypermetabolism 194 hypertrophic cardiomyopathy 353 hypokalaemia 292–3 hyponatraemia 223, 262 hypoplastic left heart syndrome 354 hypothermia 72, 388 hypothyroid state 71–2 hypoxanthine 90, 92 hypoxia-inducible factor (HIF-1) 88 I idiopathic pulmonary fibrosis 321–2, 324 illicit substance use 206 immunizations, pretransplant 240, 261 immunology 99–105 pharmacological modulation of immune response 101–5 tissue rejection 99–101 tissue typing and organ matching 101 xenotransplantation 112–14 immunosuppression agents 101–5 geriatric transplantation 377, 380 heart transplantation 312, 342, 343 history of 4–5 induction therapy 105 intestinal and multivisceral transplantation 282, 300–1, 302 islet cell transplantation 172, 174, 176 kidney–pancreas transplantation 148, 156 kidney transplantation 156 lung transplantation 348 maintenance therapy 105 non-transplant surgery 420–1 paediatric liver transplantation 269 pancreas transplantation 148, 156 pregnancy after transplantation 430–1 protocols 105 xenotransplantation 112, 116–17 index of covariance 50 infection cell salvage 410 fibrosis 101 heart transplantation 311, 342–3 intestinal and multivisceral transplantation 299 kidney–pancreas transplantation 153–6 kidney transplantation 153–6, 375 liver disease 193–4, 217–18 liver transplantation 239–40 lung transplantation 347–8 non-transplant surgery 421–2 paediatric heart transplantation 360 paediatric liver transplantation 271–2 pancreas transplantation 153–6 pretransplant screen 145 TEG®effects 399 transfusion-related 391 informed consent 25, 35–6, 79, 81–2 inhaled nitric oxide 311, 333 inosine monophosphate dehydrogenase inhibitors 104 index insulin 72, 142, 156, 167 Intensive Care Units 5; see also critical care International Society for Heart and Lung Transplantation (ISHLT) 21 intestinal transplantation abdominal wall closure 281–2 anaesthesia maintenance 281 arterial line 280 cardiovascular risk 279 central venous lines 281 contraindications 278, 280 critical care 297–302 definition 277 dissection phase 281 early extubation 297 endoscopic surveillance 299, 301 GI tract reconstruction 281 graft perfusion and viability 297 graft versus host disease 299–300 haematological monitoring 298 history of 7 immunosuppression 282, 300–1, 302 indications 278, 279 infection control 299 intraoperative management 281 intraoperative monitoring 279–81 living donors 286 nutrition 298 paediatrics, see paediatric intestinal and multivisceral transplantation postoperative management 282–3, 297–8 post-transplant lymphoproliferative disorder 299, 302 pregnancy and 435–6 pretransplant assessment 278–9 pulmonary artery catheter 280 quality of life 301–2 rejection surveillance 299 renal function 297 reperfusion 281 surgical technique 281–2 survival rates 277 tube feeding 283 vascular access 279 vascular anastomosis 281 intra-abdominal pressure 271 intracranial hypertension 213–15, 268 intracranial pressure monitors 404 intraoperative cell salvage, see cell salvage intravenous immune globulins 104 Iran Iranian Network for Organ Procurement 20 transplant tourism 56 ischaemia 87–91 ischaemia–reperfusion injury (PGD) 242–3, 256, 318, 333, 346–7 ischaemic heart disease 225–6 ischaemic preconditioning 95 islet cell transplantation 171–7 adverse events 175–6 allogeneic transplant 171 autologous transplant 171 autotransplant 172 benefits 175 cell isolation and processing 172 clinical monitoring 174 concomitant therapy 174 costs issues 176 exclusion criteria 173 extrahepatic sites 172, 176–7 graft function monitoring 174–5 hypoglycaemia prevention 175 immunosuppression 172, 174, 176 indications 171–2, 173 insulin independence 175 outcomes 175 progressive loss of insulin independence 176 stem cells 176 transplantation techniques 172 xenotransplantation 117, 176 islets of Langerhans 142–3, 166 Israel, transplant tourism 55 J Japan Organ Transplant Network 20 jugular venous oximetry 404–5 K ketorolac 135 kidney disease, global context 53 kidney–pancreas transplantation acute rejection 149 anaesthesia induction 145–6 anaesthetic management 144–7 antithrombotic prophylaxis 148 arterial in-flow 143 arterial lines 145 bladder drainage 143, 148, 149 burnt-out pancreas 149 cardiac complications 159–61 central venous catheters 145 chronic rejection 149 CMV prophylaxis 148 coronary artery disease screening 159 critical care 153–61 diabetes recurrence 149 diabetic patients 167–9 donor duodenum culture 148 enteric drainage 143 fluid management 146, 158 glucose control 156 haemorrhage 161 history of 7 hypercoagulability 148 immunosuppression 148, 156 infection complications 153–6 infection screen 145 intra-abdominal infections 155 intraoperative planning and care 145 kidney-first 144 laparoscopic and robotic approach 143 metabolic care 146 obese patients 145 operative management 147–8 outcomes 148–9 pancreas-first 143–4 postoperative analgesia 147 postoperative care 147, 148–9 postoperative scans 148 pretransplant evaluation 144–5 regional analgesia 146 reoperation 148 reperfusion 146–7, 148 respiratory failure 156–9 surgical technique 143–4 TEG® 148 thrombotic complications 149, 161 urinary tract infections 155 vascular complications 161 venous drainage 143 kidney transplantation ABO-incompatible 125 aetiology of ESRD 125–6 anaesthetic choice 134–5 anaesthetic management 134–6 candidate selection 128 cardiac surveillance on waiting list 132–3 cardiovascular complications 159–61, 374–5 cardiovascular risk 127, 131–3 coronary artery disease 127, 131, 132, 159 coronary revascularization 127, 132 critical care 153–61 delayed graft function 82–3 donor exchange programmes 125 donor-specific antibodies 125 double-J-ureteral stent 137–8 early referral 125 elderly 26, 45, 374–5 fluid management 135–6, 158 funding 15–16 glucose control 156 haemodynamic management 134, 135–6 haemorrhage 161 history of 3, 6 immunosuppression 156 indications 125–6 infection complications 153–6, 375 intra-abdominal infections 155 living donors 125, 375 455 456 index kidney transplantation (Cont.) logistics 25–6 muscle relaxants 134 non-transplant surgery 423–4 NSAID use 135 organ allocation 26, 44–5, 49–50 outcome 374–5 paediatrics 138 postoperative analgesia 125 postoperative ICU admission 138 pre-emptive 125 pregnancy and 433–4 premedication 134 pretransplant evaluation 126–8 pulmonary evaluation 133–4 reperfusion 137 respiratory failure 156–9 smoking 127, 133 surgical technique 136–8 survival 374–5 thrombotic complications 161 urinary tract anastomosis 137–8 urinary tract infections 155 U-stitch 138 vascular anastomosis 137 vascular complications 161 xenotransplantation 111, 117 killing/letting die distinction 36 KIR 99 Krebs cycle 88 L lactic acidosis 415 Latin America 439–40, 441 legislation, see regulation leucocyte depletion filters 409 leucodepletion 387 levosimendan 310, 331 liberation from ventilation 158 life years after transplant 48 LiMax test 243 live liver donors 9, 26, 195, 230, 251–6 anaesthetic agents 252 blood transfusion 254 central venous pressure monitoring 252–3 donor assessment 251–2 donor morbidity and mortality 255–6 fluid management 253–4 information provision 251 intraoperative management 252–5 intraoperative monitoring 252–3 ischaemia–reperfusion injury 256 laparoscopic techniques 256 left lobe grafts 255 liver regeneration 255 postoperative management 254–5 postoperative pain 255 preoperative assessment 252 prophylactic therapy 252 liver anatomy and physiology 184 elderly patients 372 neurological death 71 regeneration 255 liver disease acute versus chronic liver failure in children 265 clinical manifestations in children 259–61 critical care 211–20 elderly 372–3 end-stage 184, 194–5, 211, 213, 215, 216, 217–18, 219, 224–5, 259, 260–1 epidemiology 183–4 trends 9 viscoelastic haemostatic assays 399 see also acute liver failure;chronic liver disease; hepatocellular carcinoma liver–intestine–pancreas transplantation 288 liver–intestine transplantation 278 liver–kidney transplantation 208 liver support systems 218–19, 262, 268 liver transplantation acute liver failure 201, 207, 212–13 age 204–5 alcohol misuse 205–6 anaesthetic management 8, 230–5 anaesthetic technique 230 anhepatic phase 228 antifibrinolytic therapy 8–9 blood products 232, 389 cardiovascular function 205, 224, 225–7, 231–2, 374 cardiovascular monitoring 231 cava-cavaplasty 228 caval replacement versus preservation 7–8, 288–9 cell salvage 232, 407, 409–10 cerebral monitoring 403–4 children, see paediatric liver transplantation chronic liver disease 195, 201–2, 207 classical (caval replacement) technique 7–8, 228 CNS function 225 coagulopathy management 223, 225, 231, 233–4 contraindications 203–4, 228 critical care 239–47 diabetes mellitus 205 dissection phase 228 donor risk index 379 early extubation 9, 235, 239 EEG 403–4 elderly 372–4 electrolytes 224, 234–5 enteral feeding 244 extrahepatic malignancy 206 fast-tracking 9 fluid management 232–3, 415 glucose control 235 graft function assessment 240–2 haemodynamic management 225, 400–5 hepatocellular carcinoma 201, 202, 207 hepatopulmonary syndrome 227 high urgency requests 26 history of 7–9 HIV 206 HIV–HCV co-infection 206 hyperkalaemia 223, 415 hyponatraemia 223 indications 195, 201–2 infection prophylaxis 239–40 inferior vena cava clamping 228, 231 initial poor function 242 intracardiac thrombosis 233–4 intracranial pressure monitors 404 intraoperative monitoring8, 230–1 ischaemia–reperfusion injury 242–3 jugular venous oximetry 405 lactic acidosis 415 LiMax test 243 living donors, see live liver donors logistics 26 MELD score mental status 241 metabolic changes 224, 234–5 near-infrared spectroscopy 403 non-transplant surgery 424 nutritional management 205, 227, 244 obesity 205, 227 oesophageal Doppler 402–3 organ allocation 9, 26, 206–7 outcome 195, 207–8, 373–4 paediatrics, see paediatric liver transplantation paracetamol hepatotoxicity 202, 207 parenteral feeding 244 peripheral arterial waveform analysis 402 piggyback (caval preservation) technique 7–8, 228–9 portal vein unclamping 232 portopulmonary hypertension 227, 401 postoperative care 9 pregnancy and 432–3 preoperative evaluation 223–8 preoperative preparation 230 pretransplant evaluation 202–3, 204 pretransplant immunization 240 primary graft dysfunction 242–3 prioritization of recipients 206–7 prognosis 195 pulmonary artery catheter 8, 401–2 pulmonary hypertension 227, 232 rapid infusion systems 9, 410 index referral guidance 207 removal of critically ill patients from waiting list 219–20 renal function 206, 223, 224, 225, 227, 232 reperfusion 229, 232 respiratory function 224, 227, 235 retransplantation 208 sepsis 228 seventh day syndrome 243 smoking 206 split grafts 195 substance misuse 206 super-urgent 201, 202, 213 surgical techniques and procedures 228–30 survival 373–4 TEG® 8, 231, 395 timing of referral 201 TOE 231, 402 transcranial Doppler 403 UKELD score 201–2 urine output 241 vascular access 230 venovenous bypass 8, 229–30 viscoelastic haemostatic assays 395, 398 waiting list management xenotransplantation 111, 117 living donors 66 donor selection 23–4 ethics 35–6 growth in programmes 9–10 intestinal transplantation 286 kidney transplantation 125, 375 see also live liver donors logistics 25–7 low potassium dextran 325 lung allocation score (LAS) 27 lung-protective strategies 70, 78 lung transplantation acute rejection 347 airway complications 349 anaesthesia induction 328–9 anaesthesia maintenance 330–1 anaesthetic management 327–33 antifibrinolytics 332 bridge to 327 bronchial stenosis 349 bronchiolitis obliterans 425 cardiopulmonary bypass 331–2 children 362–3 complications 346–49 contraindications 326 cystic fibrosis 322–3, 328, 329, 348, 362 donor organ management 324–6 donor selection 324 double lumen tubes 329 dysrrhythmias 348 early mobilization 346 extracorporeal membrane oxygenation 326–7, 332 ex-vivo lung perfusion 325–6 fluid management 332, 345 gastrointestinal complications 349 haemodynamics 345 history of 6 immunosuppression 348 indications 321, 323 infection risk 347–8 intensive care 344–49 interoperative setup and monitoring 326–7 ischaemic time 325 logistics 27 lung allocation score (LAS) 27 lung preservation 324–5 neurological complications 347 non-transplant surgery 425 obstructive lung disease 321, 328, 329 organ allocation 27 paediatrics 362 patient positioning 330 plasmapheresis 332 pneumonia development 347–8 postoperative analgesia 333, 345–6 postoperative management 334, 344–5 preoperative assessment and management 327–8 primary graft dysfunction 333, 346–7 pulmonary vascular disease 323–4, 328–9 recipient selection 326 renal complications 347 reperfusion 332–3 restrictive lung disease 321–2, 328, 329 right ventricular dysfunction 331 suppurative lung disease 322–3, 328, 329, 348 survival 321 thoracic epidural anaesthesia 333, 346 TOE 329–30 ventilator management and weaning 345 M magnetic resonance angiogram 62 major histocompatibility complex (MHC) 99 major incompatibility 385 malignancy cell salvage 409–10 heart transplantation 344 non-transplant surgery 422 paediatric heart transplantation 360 pre-liver transplantation 206 malnutrition 194, 203, 205 mandated data submission 447–8 mannitol 136 marketing organs 38–9, 53–7 MARS® 218–19, 262, 268 massive transfusion 72, 319, 388–9 mechanical circulatory support 357–8 mechanical ventilation 157–8, 216–17 medical competency 441–2 melatonin 246 MELD score 9, 185–6, 187, 289 memantine 246 mentorship 442 metabolic systems elderly 362 kidney–pancreas transplantation 146 liver transplantation 224, 234–5 neurological death 71–2 pancreas transplantation 146 methylprednisolone 78, 102 MICA/MICB 99 microchimerism 391–2 microvascular failure 91 midazolam 270 milrinone 310, 331, 361 minor histocompatibility antigens (mHags) 99 minor incompatibility 385 mitochondrial permeability transition (pore) 93–4 mixed chimerism 112–13 mixed venous oxygen saturation 402 monoclonal antibodies 102–3, 104, 421 moral issues 34–5, 36–8 mTOR inhibitors 104–5, 421 multivisceral transplantation abdominal wall closure 281–2 anaesthesia maintenance 281 arterial line 280 cardiovascular risk 279 central venous lines 281 complications 376 contraindications 278, 376 critical care 297–302 definition 277 dissection phase 281 early extubation 297 elderly 375–6 endoscopic surveillance 299, 301 fluid management 376 GI tract reconstruction 281 graft perfusion and viability 297 graft versus host disease 299–300 haematological monitoring 298 history of 7 immunosuppression 282, 300–1, 302 indications 278 infection control 299 intraoperative management 281 intraoperative monitoring 279–81 non-transplant surgery 424 nutrition 298 outcome 375–6 457 458 index multivisceral transplantation (Cont.) paediatrics, see paediatric intestinal and multivisceral postoperative management 282–3, 297–8 post-transplant lymphoproliferative disorder 299, 302 pretransplant assessment 278–9 pulmonary artery catheter 280 quality of life 301–2 rejection surveillance 299 renal function 297 reperfusion 281 surgical technique 281–2 tube feeding 283 vascular access 279 vascular anastomosis 281 mycophenolate mofetil 104, 420–1, 430 mycophenolic acid 104 myocardial ischaemia 160–1 myocardial stress scintigraphy 159 N National Organ Transplant Act (1984) 14 naturally occurring antibodies 385 near-infrared spectroscopy 403 necrosis 92 neurological death children 63 determination 61–3 donor management goals 72 organ function 64–6 pathophysiology 69–72 neurological function elderly 372 geriatric transplantation 380 hepatic encephalopathy 191, 213–14, 215, 244–6, 261, 262, 268 lung transplantation 347 non-transplant surgery 422 neurosteroids 245 neurotransmission 246 new transplant programmes 439–43 NF-κB 92 NHS Blood and Transplant 25 non-alcoholic fatty liver disease 183, 184 non-heart-beating donors 23 non-invasive ventilation 157, 158–9 non-transplant surgery 419–26 anaesthetic management 422–3 electrolytes 423 glycaemic control 423 haemodynamic control 423 heart transplant recipients 424–5 immunosuppression 420–1 infections 421–2 intraoperative monitoring 423 kidney transplant recipients 423–4 liver transplant recipients 424 lung transplant recipients 425 multivisceral transplant recipients 424 neurological complications 422 perioperative management 419–20 postoperative analgesia 425–6 postoperative management 425–6 post-transplant malignancies 422 preoperative evaluation 422 rejection 421 Noonan’s syndrome 353 no-reflow phenomenon 91 norepinephrine 245 normal saline 254 North American Transplant Coordinators Organization (NATCO) 21 NSAIDs 135 nuclear imaging 63 nutrition 194, 203, 205, 227, 244, 260–1, 272, 298 O obesity 145, 205, 227 obstructive lung disease 227, 321, 328, 329 oesophageal Doppler 402–3 oesophageal varices 186–8 OKT3 421 opioids, liver resection 255 opt-in systems 20 OPTN/UNOS committees 14 opt-out systems 20–1, 36–8 organ allocation 43–51 authority and 46–7 efficiency 47–8 equity 50–1 geographic boundaries in US 15 kidney transplantation 26, 44–5, 49–50 liver transplantation 9, 26, 206–7 logistics 25–7 OPO responsibilities 19 outcomes and 45 pancreas transplantation 26–7 principles 46–51 property rights 39, 46 shortage of organs 43–6 thoracic organs 27 trends 9 utility 48–50 waiting-time based 50–1 organ donation altruism 54 authorization process 18–19, 20–1, 39–40 clinical donor management 19 critical are 64–6, 69–74 development of systems in US 13–21 donor management goals 72–3, 78 ethics 33–41 exploitation 56 family support 18–19, 39–40 HIV-positive 15 interhospital sharing 13 opt-in systems 20 opt-out systems 20–1, 36–8 recovery of organs 19, 73–4 regional sharing 13 regulation 10, 13–21, 24–5, 45–6 research in 77–83 signing up on registries 17 trends 9 vendors 38–9, 53–7 organ matching 101 organ preservation 5, 90–1, 96, 324–5 Organ Procurement and Transplantation Network (OPTN) 14 organ procurement organizations (OPOs) performance measurement 16–17 responsibilities 17–19 structure 15–16 organ recovery critical care considerations 73–4 OPO responsibilities 19 organ resuscitation 94–6 organ sharing systems 19–20 organs transplanted per donor 17 organ transplant continuum 87–93 outcomes kidney–pancreas transplantation 148–9 kidney transplantation 374–5 liver transplantation 195, 207–8, 373–4 multivisceral transplantation 375–6 new transplant programmes 442–3 organ allocation and 45 paediatric heart transplantation 359–60 paediatric lung transplantation 363 pancreas transplantation 148–9, 377 oxidative stress 246 oxindole 245 P pacing 311, 340 paediatric heart transplantation 353–62 ABO-incompatible 358–9 anaesthesia induction 361 anthracycline-induced cardiomyopathy 353 anti-HLA antibodies 357 bridge to 357–8 cardiac allograft vasculopathy 360 cardiomyopathies 353–5 congenital heart disease 354 contraindications 356–9 dilated cardiomyopathy 353–4 donation after cardiac death 359 failed Fontan 355–6 history of 353 hypertension 360 hypertrophic cardiomyopathy 353 index hypoplastic left heart syndrome 354 indications 353–6 infection risk 360 intraoperative management 361 malignancy 360 outcomes 359–60 postoperative management 361–2 post-transplantation surveillance 360 preoperative assessment 360–1 pretransplant assessment 355 pulmonary hypertension 361–2 pulmonary vascular resistance 357 rejection 360 renal dysfunction 360 restrictive cardiomyopathy 354–5 retransplantation 355 right ventricular failure 361 survival 359–60 paediatric intestinal and multivisceral transplantation 285–93 abdominal wall closure 288 anaesthesia induction and maintenance 291 anaesthetic management 288–93 arterial line 291 blood products 290 central venous access 290–1 coagulopathy 293 contraindications 286–7 donor assessment and selection 285–6 GI tract reconstruction 288 glycaemic control 293 hyperglycaemia 293 hyper-/hypokalaemia 292–3 hypotension 292 indications 286 intraoperative indices 292 living donors 286 operating room preparation and equipment 290–1 preoperative assessment 288–90 quality of life 301–2 surgical technique 287–8 vascular anastomosis 288 paediatric kidney transplantations 138 paediatric liver transplantation abdominal compartment syndrome 271 acute liver failure 264–5 anaesthesia induction 262 anaesthetic management 262–5 anhepatic phase 263–4 anti-acid medication 269 antibiotics 269 antiplatelets 270 blood products 271 cardiovascular function 259–60, 270 cell salvage 263 central venous access 262–3 clinical manifestations of liver disease 259–61, 267–8 critical care 267–73 dissection phase 263 enteral feeding 272 failure to wean 272–3 fluid management 263, 270–1 gastrointestinal bleeding 272 graft dysfunction/thrombosis 272 hyponatraemia 262 immunosuppression 269 indications 259, 260 infection control 271–2 intraoperative management 262–5 intraoperative monitoring 262, 263 investigation of liver disease 261 nutrition 260–1, 272 PELD score 261 postoperative analgesia 270 postoperative care 270–2 postoperative sedation 270 preoperative assessment 262 principles of intensive care 269 rejection 272 renal function 260 reperfusion 264 respiratory function 260, 270 retransplantation 265 seizures 271 surgical technique 263–4 temperature control 263 vaccinations 261 ventilation 270, 272–3 waiting list management 261 paediatric lung transplantation 362–3 pain relief, see postoperative analgesia palliative care 268–9 pancreas, anatomy and physiology 141 pancreas transplantation acute rejection 149 anaesthesia induction 145–6 anaesthetic management 144–7 antithrombotic prophylaxis 148 arterial in-flow 143 arterial line 145 bladder drainage 143, 148, 149 blood supply to graft 141–2 burnt-out pancreas 149 cardiac complications 159–61 central venous catheter 145 chronic rejection 149 CMV prophylaxis 148 coronary artery disease screening 159 critical care 153–61 diabetes recurrence 149 diabetic patients 167–9 donor duodenum culture 148 elderly 376–7 enteric drainage 143 fluid management 146, 158 glucose control 146, 156 haemorrhage 161 history of 7 immunosuppression 148, 156 infection complications 153–6 infection screen 145 intra-abdominal infections 155 intraoperative planning and care 145 logistics 26–7 metabolic care 146 obese patients 145 operative management 147–8 organ allocation 26–7 outcome 148–9, 377 physiology of graft 142–3 postoperative analgesia 147 postoperative care 147, 148–9 postoperative scans 148 P-PASS score 27 pregnancy and 436 pretransplant evaluation 144–5 regional analgesia 146 renal function evaluation 145 reoperation 148 reperfusion 146–7, 148 respiratory failure 156–9 surgical technique 143–4 thrombotic complications 149, 161 urinary tract infections 155 vascular complications 161 venous drainage 143 xenotransplantation 117 paracetamol hepatotoxicity 202, 207 parenteral feeding 244 passenger lymphocyte syndrome 385 patent foramen ovale 329 patient blood management 389–91 patient-centred outcomes 442–3 patient satisfaction 449 PCP pneumonia 240 PELD score 186, 261, 289 Perfadex® 325 perfusion preservation 5, 91, 96 peripheral arterial waveform analysis 402 peroxynitrite 92 pharmacological preconditioning 95–6 pharmacology elderly 372 heart transplantation 341 liver disease 194–5 phosphofructokinase 88 physiological stability 153 PiCCO system 402 pig organs, see xenotransplantation Plasmalyte™ 254 Plasmapheresis 332 plastic bronchitis 354 platelet function 397–8 459 460 index platelet transfusion 386 Pneumocystis jirovecii 240 pneumonia 193, 240, 347–8 Pompe’s disease 353 portal hypertension 186–8 portopulmonary hypertension 192, 227, 401 postconditioning 96 post-ischaemia–anoxia 91–3 postoperative analgesia kidney–pancreas transplantation 147 kidney transplantation 125 live liver donors 255 lung transplantation 334, 345–6 non-transplant surgery 425–6 paediatric liver transplantation 270 pancreas transplantation 147 postoperative delirium 380 postoperative management/monitoring geriatric transplantation 380 heart–lung transplantation 319 heart transplantation 311–12, 339–40 intestinal and multivisceral transplantation 282–3, 297–8 kidney–pancreas transplantation 147, 148–9 live liver donors 254–5 liver transplantation lung transplantation 334, 344–5 non-transplant surgery 425–6 paediatric heart transplantation 361–2 paediatric liver transplantation 270–2 pancreas transplantation 147, 148–9 xenotransplantation 116 post-transplant lymphoproliferative disorder 299, 302, 360 P-PASS score 27 Preconditioning 95–6 prediction models 49–50 pregnancy after transplantation 429–36 graft function evaluation 429–30 heart–lung transplantation 434–5 heart transplantation 434–5 immunosuppression 430–1 intestinal transplantation 435–6 kidney transplantation 433–4 liver transplantation 432–3 pancreas transplantation 436 timing of pregnancy 429 pre-ischaemia 87 preload 340 preoperative assessment geriatric transplantation 377–9 heart–lung transplantation 315–16 heart transplantation 307–9 live liver donors 252 liver transplantation 223–8 lung transplantation 327 non-transplant surgery 422 paediatric heart transplantation 360–1 paediatric intestinal and multivisceral transplantation 288–90 paediatric liver transplantation 262 pre-preservation 87–90 preservation of organs 5, 90–1, 96, 324–5 pressure–time product 157 presumed consent 20–1, 24 pretransplant evaluation intestinal and multivisceral transplantation 278–9 kidney–pancreas transplantation 144–5 kidney transplantation 126–8 liver transplantation 202–3, 204 paediatric heart transplantation 355 pancreas transplantation 144–5 primary biliary cirrhosis 183, 373 primary graft dysfunction lung (I–R injury) 242–3, 256, 318, 333, 346–7 primary pulmonary hypertension 323–4 prisoners, organ donors 55 professional societies 21 Program-Specific Reports 448 property rights 39, 46 prostacyclin 311 prostaglandin 311, 333 proteasome inhibitor 103–4 protein-losing enteropathy 354 prothrombin time 400 public education 17 pulmonary arterial hypertension 323 pulmonary artery catheters 8, 70, 280, 401–2 pulmonary artery occlusion pressures 402 pulmonary hypertension 227, 232, 307, 309, 361–2 pulmonary vascular disease 323–4, 328–9 pulmonary venous–left atrial anastomoses 329 purine analogues Q QAPI programme 448 quality control 441 quality improvement 448–9 quality of life 301–2 R rabbit ATG 102 rapamycin (sirolimus) 104–5, 282, 421, 430 rapid infusion systems 9, 410–11 reactive oxygen species 91–2 recovery of organs critical care considerations 73–4 OPO responsibilities 19 red cell alloimmunization 386, 388 red cell irradiation 387–8 red cell storage lesions 386 regulation 10, 13–21, 24–5, 45–6, 447 rejection acute 100, 149, 272, 299, 312, 343–4, 347 chronic 100–1, 149 classification 343, 344 delayed xenograft 113–14 heart transplantation 312, 343–4 history of 3–4 hyperacute 112 immunobiology 99–101 intestinal and multivisceral transplantation 299 lung transplantation 347 non-transplant surgery 421 paediatric heart transplantation 360 paediatric liver transplantation 272 pancreas transplantation 149 remote ischaemic preconditioning 95 renal function elderly 372 heart–lung transplantation 316 intestinal and multivisceral transplantation 297 liver disease 194, 217, 260, 268, 416 liver transplantation 206, 223, 224, 225, 227, 232 lung transplantation 347 neurological death 71 paediatric heart transplantation 360 pancreas transplantation 145 renal replacement therapy 44, 411–16 global context 53 indications 411 intraoperative 415–16 liver disease 217, 416 principles 412 requirements for 412–15 reoxygenation injury 91–2 reperfusion injury 91–3 research, organ donors 77–83 respiratory failure kidney–pancreas transplantation 156–9 kidney transplantation 156–9 liver disease 216–17 pancreas transplantation 156–9 respiratory function elderly patients 371–2 geriatric transplantation 380 liver transplantation 224, 227, 235 neurological death 70 paediatric liver disease 260 paediatric liver transplantation 270 restrictive cardiomyopathy 354–5 restrictive lung disease 321–2, 328, 329 retransplantation liver transplantation 208 paediatric heart transplantation 355 paediatric liver transplantation 265 right ventricular failure 318, 331, 341–2, 361 index right ventricular outflow tract obstruction 329–30 Ringer’s solution 136, 254 risk tolerance 45–6 rituximab 103, 300 ROTEM® (rotational thromboelastometry) 231, 395–400 S Scandiatransplant 25 sedation 217, 270 seizures 271 selling organs 38–9, 53–7 sepsis 153–4, 216, 218, 228, 240, 347–8, 380 septic shock 153–4 serotonin 245–6 seventh day syndrome 243 severe sepsis 153–4 shared agency 40 short bowel syndrome 277, 278, 285 sildenafil 311 sirolimus (rapamycin) 104–5, 282, 421, 430 Six Sigma 449 smoking 127, 133, 206 social worth 48–9 soft presumed consent 21 Southeastern Regional Organ Procurement Program (SEROPP) 13 Southeast Organ Procurement Foundation (SEOPF) 13 Spain 19–20, 34 spontaneous bacterial peritonitis 189 standard acquisition charge 16 standard criteria donors (SCD) 17, 66 standardized protocols 441 statins 378 stem cells 176 steroids 4, 5, 70, 72, 78, 102, 420, 431 steroid-sparing protocols 105 substance misuse 206 suicide right ventricle 330 superoxide 92 suppurative lung disease 322–3, 328, 329, 348 survival hearttransplantation 307 intestinal and multivisceral transplantation 277 kidney transplantation 374–5 liver transplantation 373–4 lung transplantation 321 measurement 48 paediatric heart transplantation 359–60 paediatric lung transplantation 363 Surviving Sepsis Campaign 154 sympathetic storm 69 systemic inflammatory response syndrome (SIRS) 70 T T3 and T4 71–2 tacrolimus 104, 282, 297, 300, 420, 431 T-cell depletion 113 T-cell-mediated acute rejection 100 TEG® 8, 148, 231, 395–400 tetrahydrodeoxycorticosterone 245 TGR 5, 245 thermoregulation 72 thoracic epidural anaesthesia 333, 346 thrombocytopaenia 193 thromboelastography (TEG®) 8, 148, 231, 395–400 thrombotic microangiopathy 298 thymectomy 115 thymic tissue transplantation 112–13 thymoglobulin 102, 421 thymokidney 113, 114, 116 thyroxine 71–2 TIPS 189–91 tissue-specific antigens 99 tissue typing 101 tolerance induction 116–17 strategies 112–13 trafficking in organs 55–7 training 442 tranexamic acid 310–11, 332 transcranial Doppler 63, 403 transfusion-associated circulatory overload 391 transfusion medicine 385–92 transfusion-related acute lung injury 391 transfusion-related immunomodulation 391 transjugular intrahepatic portosystemic shunt (TIPS) 189–91 transoesophageal echocardiography (TOE/TEE) 231, 309, 317, 329–30, 402 transplant tourism 53–7 transpulmonary gradient 308–9 transversus abdominis plane block 255 tromethamine 158 trust 35–6 tuberculosis 240 U UKELD score 201–2 unconsciousness 62 UNetSM 14 Uniform Anatomical Gift Act (2006) 13 United Network for Organ Sharing 14 urinary tract infections 155 usual interstitial pneumonia 321–2, 324 utility 48–50 UW solution V vaccination, pretransplant 240, 261 valganciclovir 240 varices 186–8 vascularized thymic lobe transplantation 113 vasopressin 70, 71 venovenous bypass 8, 229–30 ventilation ALI/ARDS 157–9 liver disease 216–17 lung transplantation 345 organ donors 70 paediatric liver transplantation 270, 272–3 ventricular assist devices 342, 357 viscoelastic haemostatic assays 395–400 W waiting list management 9, 261, 307 waiting-time based allocation 50–1 warm ischaemia 91 work of breathing 157 X xanthine oxidase 90, 92 xenotransplantation 111–17, 176 advantages 114 bridge to allotransplantation 117 delayed rejection 113–14 donor procedures 115–16 donor selection and preparation 114 donor species choice 111–12 history of 111 immunology 112–14 immunosuppression 112, 116–17 postoperative management 116 pretransplant recipient procedures 115 recipient selection and preparation 114 , 116 renal procurement 116 surgical approach 114–15 thymokidney 113, 114, 116 tolerance induction 116–17 tolerance strategies 112–13 461 .. .Oxford Textbook of Transplant Anaesthesia and Critical Care Oxford Textbooks in Anaesthesia Oxford Textbook of Anaesthesia for the Elderly Patient Edited... Professor of Medicine and Director Division of Hepatology University of Miami Leonard M Miller School of Medicine Miami Florida USA Professor of Clinical Surgery DeWitt Daughtry Department of. .. burgeoning field of transplant anaesthesia and critical care As you will see on initial perusal of the table of contents we have taken a holistic approach to the scope of practice of transplant anaesthesia