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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN THANH KHIEM RESEARCH ON THE APPLICATION OF THE LIVER PROCUREMENT PROCEDURE I[.]
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES - NGUYEN THANH KHIEM RESEARCH ON THE APPLICATION OF THE LIVER PROCUREMENT PROCEDURE IN BRAIN-DEAD DONORS Specialty: Gastroenterological Surgery Code: 62720125 ABSTRACT OF MEDICAL PhD DISSERTATION Hanoi – 2023 The thesis was done in: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: Prof MD PhD Trinh Hong Son Assioc Prof MD PhD Nguyen Tien Quyet Reviewer 1: Reviewer 2: Reviewer 3: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences LIST OF RELATED PUBLICATIONS Thanh Khiem Nguyen, Hong Son Trinh, Tuan Hiep Luong et al technical characteristics and quality of grafts in liver procurement from brain-dead donors: A single-center study in Vietnamese population Annals of Medicine and Surgery 69 (2021) 102654 Thanh Khiem Nguyen, Hong Son Trinh, Gia Anh Pham et al Clinical and subclinical characteristics of brain-dead donors for liver transplantation in Viet Duc University Hospital Vietnam Journal of Science, Technology and Engineering 63(4),36-41 INTRODUCTION Organ transplantation in general, and liver transplantation in particular, is one of the most outstanding medical achievements of the past few decades However, the transplant field has always faced the problem of scarcity of donated organs for all organs and especially the liver Liver from brain-dead donors is the most common form, times more than from living donors The world's first successful liver transplant was performed by T Starzl in 1967 In Vietnam, through the project "Research on implementation of liver-kidney transplantation from brain-dead donors" (code KC10.25/06-10), the liver procurement procedure from a brain-dead donor was successfully implemented at Viet Duc University Hospital in 2010 Choosing a brain-dead donor plays a very important role Considering the clinical and paraclinical factors of brain-dead donors appropriately helps to between increasing the number of grafts and ensuring graft quality as well as post-transplant outcomes The organ procurement procedure is also the key to having a good graft both anatomically and functionally Any technical mistakes can lead to irreversible organ damage In Vietnam, there has been no research to answer two the question: which are characteristics of brain-dead people suitable for liver criteria? and secondly, is the liver procurement procedure developed and applied at Viet Duc University hospital effective? Therefore, we carried out the project "Research on the application of the liver procurement procedure in brain-dead donors" with two objectives: Describe some clinical and paraclinical characteristics of brain-dead donors Evaluation of the application results of the liver procurement procedure in brain-dead donors Chapter LITERATURE REVIEW 1.1 Diagnosis of brain death Brain death is defined as the irreversible cessation of brain functions including the brainstem Common causes of brain injuries are severe traumatic brain injury (TBI), cerebrovascular accidents (including diseases caused by hypertension and vascular malformations), brain tumors, etc The standard for diagnosis of brain death is prescribed in the "Law on donation, collection and transplantation of human tissues and organs and donation and collection of corpses" of the National Assembly 1.2 The liver procurement procedure from brain-dead donors The liver procurement procedure from a brain-dead donor was codified by T Starzl in 1984 and is now written in many textbooks In Vietnam, this process was developed and applied in 2010 at Viet Duc University Hospital through the Project "Research and implementation of liver-kidney transplantation from brain dead donors", Code KC10.25/06-10 There are differences in some technical points between the authors, but they all include main stages: laparotomy, exploration; vascular preparation; refrigeration and organ removal In the braindead donor, the liver is taken mainly in the multiple organs In the step of vascular preparation, there are two basic techniques “Warm dissection”: control blood vessels and hepatic pedicle components before cannula placement and organ washing “Cold dissection” performs the fastest possible maneuvers to wash and cool the organ, sometimes requiring only the insertion of a lavage line into the aorta “Warm dissection” helps to concentrate the perfusion fluid to each anatomical area, reducing the time of ischemia, making it easy to remove the liver in cold phase “Cold dissection” is a quick, simple technique that is beneficial when the donor hemodynamics are unstable 1.3 Study on clinical and paraclinical characteristics of braindead organ donors 1.3.1 In the world The ideal criteria of a brain- dead liver donor include factors such as: age < 40 years, cause of brain death due to TBI, hemodynamic stability until organ removal , non-fatty liver, and no chronic and contagious liver disease The most common current extended criteria are Briceno's criteria including: age > 60 years, length of ICU stay > days, duration of cold ischemia > 13 hours, mean BP < 60 mmHg lasting more than hour , total bilirubin > 2.0 mg/dL, ALT > 170 U/L and/or AST > 140 UI/L, dopamine dose >10 µg/kg/min and blood sodium > 155 mmol/L Criteria for selecting a donor are the basis for studying the clinical and paraclinical characteristics of brain-dead organ donors Research results of foreign authors show that selection criteria are increasingly expanded according to age, cause of brain death, infection status, degree of steatosis, etc 1.3.2 In Vietnam Just like in the world, although the studies in Vietnam appeared much later, they also followed two approaches above The first is that the research related to anesthesia resuscitation when brain-dead organ transplant began to develop in Vietnam since 2010 Only two studies by author Trinh Hong Son have examined the characteristics of brain – dead donors related to graft outcome In the first study, the author referred to most of the clinical and paraclinical characteristics of the donor related to the outcome of liver transplantation in the French subjects The second study was conducted on Vietnamese people with all brain-dead donors in the country from April 2008 to August 2016 , although the study focused on brain death diagnosis and organ transplantation coordination, few clinical features were mentioned 1.4 Study on the results of applying the liver procurement procedure from brain-dead donors 1.4.1 In the world In the world, there have been many studies on the results of liver procurement procedure from brain-dead donors, in which the results of this procedure are evaluated in terms of the technical characteristics and the quality of graft in terms of morphology, ischemia time and results after transplantation Some issues are concerned: is the technique of "warm dissection" or "cold dissection" safer and more effective? advantages and disadvantages in technical steps; effectiveness and variation of cannula placement techniques; the effectiveness of the organ washing solution; anatomical damage of the graft; quality of liver parenchyma; graft ischemia time, etc 1.4.2 In Vietnam In Vietnam, up to now, there has not been a study that fully summarizes the results of the liver procurement procedure from a brain-dead donor Some studies are clinical reports, others only describe some general characteristics of the donor without in-depth analysis of technical issues and graft outcomes Chapter SUBJECTS AND METHODS 2.1 STUDY SUBJECTS There were 49 subjects all over 18 years old, diagnosed with brain-death, and underwent multiple organ procurement with recipients of orthotopic liver transplantation at the Viet Duc University Hospital from May 2010 to May 2020 2.1.1 Inclusion criteria * Donor - Age over 18 - The patient is determined to be brain dead by the "Expert Council to identify brain-dead patients" approved by the Director of Viet Duc University Hospital - The family agrees and has an application for organ donation - The whole liver was procured and transplanted to the corresponding recipient in Viet Duc University Hospital - Have a complete medical record * Recipient: Liver cirrhosis (MELD score over 15 points or ChildPugh score over points, decompensated cirrhosis), HCC without extra-hepatic metastasis, acute liver failure 2.1.2 Exclusion criteria * Donor: Cases of split liver transplantation or reduced-volume liver transplantation, died of cardiac arrest, graft was not transplanted or was transferred to a recipient at another hospital, patients with contraindications to liver procurement: HIV infection, pulmonary tuberculosis, acute hepatitis, extensive liver injury, gross cirrhosis, cancer, peritonitis * Recipient: Livers are taken from other hospitals Recipients of a split liver transplantation or reduced-volume liver transplantation 2.2 STUDY METHODS 2.2.1 Study design: A descriptive study 2.2.2 Sampling Convenience sampling included all patients who met the inclusion criteria during the study period 2.2.3 Study instruments Ultrasound and computed tomography machines,, laboratory tests, anesthesia and surgical equipments 2.2.4 Surgical protocol: The technical procedure for liver procurement is based on the national research named " Research on liver and kidney transplantation from brain-dead donors “, code KC10.25/06-10 2.2.4.1 Prepare the donor Completing legal procedures, resuscitation of the brain-dead donor, testing for organ donation possibility, diagnosing and declaring brain death 2.2.4.2 Technical Process - Step (Laparotomy, exploration and evaluation): explore abdominal status, liver status, liver anatomical changes to decide to take liver - Step (Vascular preparation) reveal oscillating anatomical structures required for organ washing - Step (Vascular cannulation, flush perfusion): Place suitable cannula into aorta, IVC, portal vein Cover with ice and infuse wash solution - Step (Organ procurement): Releasing the liver to liver procurement - Step (Dissection on back-table): prepare the liver on the back table to be ready for transplantation 2.2.5 Study parameters: 2.2.5.1 General characteristics: age, gender, body mass index (BMI) 2.2.5.2 Clinical and paraclinical characteristics * Clinical characteristics: Cause of brain death, time to brain death resuscitation, medical history and comorbidities, clinical systemic changes of the donors, rate of vasopressor use, bacterial and viral infections status * Paraclinical characteristics: hematology and biochemical test: red blood cell (RBC), Platelet (PLT), hemoglogbin (Hb)…; amount of blood and serum transfusion during resuscitation; assessment of graft on diagnosis imaging 2.2.5.3 Results of liver procurement procedure * Selection of donors: ideal or extended selection criteria, blood group and HLA matching * Organs procurement techniques and graft morphology: Indicators related to technical steps, macroscopic and microscopic quality of grafts, changes in hepatic artery anatomy * Post-transplant results: General characteristics of recipients, clinical and paraclinical results after transplantation, classification of post-transplant liver function, surgical complications related to the graft * Evaluation of some factors related to the donor (age group, serum sodium concentration, cold ischemia time, resuscitation time, hemodynamic disorders and graft fat degeneration) to the liver function (GOT, GPT, Total Bilirubin, INR) 2.2.6 Statistical analysis All study parameters were collected using a unifined study protocol All data were encrypted and inputted into a computer and then processed using SPSS 24.0 software Use statistical algorithms to calculate mean, percentage Using “repeat ANOVA” analysis to test the change of the mean values of the indexes over time T test used to compare means, χ2 test used for proportions, the difference was considered statistically significant when p (6) LHA originated from left gastric artery (LGA) (7) (8) Accessory LHA originated from LGA (1) RHA originated from superior mesenteric artery (SMA) and ran behind the common bile duct (CBD) (2) Accessory RHA originated from SMA, CT and SMA had the same origin (3) Accessory RHA originated from SMA CHA originated from SMA and ran behind the portal vein (PV) (1) No GDA (2), (3) The Accessory RHA originates from the gastroduodenal artery: the small branch of the right hepatic artery splits close to the base of the GDA and continues to run up the hepatic pedicle (4) The alternative RHA arises from the GDA, originates low at the superior border of the pancreas, 1.7 cm from the origin of the gastroduodenal artery, then detours down the hepatic pedicle just above the pancreas, then runs to the liver hilar before the CBD, the accessory LHA is very small from the LGA (5) The LHA dissociates prematurely from the CHA Comment: 34,7% of grafts have hepatic artery anatomical changes, of which type accounts for the highest percentage (16,3%) cases not in Hiatt’s classification in which the RHA originates from GDA There were 02 cases without detected intraoperatively, which were rare cases of RHA dissection from the GDA anterior to the CBD Three cases that need to be reconstructed are all transforms of type 15 3.3.4 Results of liver procurement procedure 3.3.4.1 General characteristics of recipients Many recipients were men (94%) and the main indication for liver transplantation was hepatocellular carcinoma (59,2%) 3.3.4.2 Graft function - 1/49 of recipients (2,0%) of recipients have PGDF 3.3.4.3 Post-transplantation complications and short-term outcome Table 3.20 Post-transplantation complications Complications N % Description Portal vein 2,04 Portal vein stenosis Biliary tract 2,04 Post-transplant cholestasis Postoperative cases unknown cause haemorrhage case with hemorrhage from 6,12 lateral branch of hepatic artery near anastomose Total 10,2 Comment: The most common complication is portal vein stenosis Table 3.28 Complications classification and outcome assessment at hospital discharge Index Complications classification (according to Clavien - Dindo) (n=49) Outcomes at hospital discharge (n=49) N % Grade I 12 24,5 Grade II 12,3 Grade III 30 61,2 Grade V 2,0 Good 48 98,0 Bad 2,0 Comment: 63,3 % had complications of grade III or higher; “Not good” outcomes on discharge occurred in cases of death 16 Chapter DISCUSSION 4.1 GENERAL CHARACTERISTICS In the study, 81.6% of the donors had an ideal age (less than or equal to 40), much lower than other studies in the world due to the disease selection process to ensure the quality of the transplant organ Male dominated 86.0% because most of the donors at Viet Duc University hospital had brain-death caused by traumatic brain injury The average body mass index (BMI) was 21.11; Only patient had BMI ≥ 25, consistent with the general biometric characteristics of Vietnamese people The results showed that BMI < 23 is a good prognostic factor and can be used as an indicator to screen for fatty liver in organ donors The study by Carpenter et al also showed that there was a difference in BMI between the groups of livers selected for transplantation and livers that were rejected after being taken from deceased donors 4.2 CLINICAL AND PARACLINICAL CHARACTERISTICS 4.2.1 Clinical characteristics 4.2.1.1 Causes and resuscitation time of brain death The most common cause of brain death is trauma (89.8%), which is different from other studies, because the rate of traumatic brain injury due to traffic accidents in Vietnam is very common The resuscitation time is only about days, and all donors have a resuscitation time of less than days, and the number of organ donors has an ideal resuscitation time of less than days accounted for 93.9%, which is different from the study of T.H Son et al with 10.8% of organ donors had a resuscitation time of days or more due to a more acute progression of severe traumatic brain injury than stroke 17 4.2.1.2 Medical history and comorbidities 4.1% of patients had systemic comorbidities, much lower than the results of T.H.Son's study on organ donors in France with the frequency of systemic comorbidities from 20.3 % to 54.1% The difference due to the cause of brain death of the two groups patients studied 4.2.1.3 Clinical systemic changes of the donors 22.45 % of patients had a period of hypotension, most of them were resuscitated well thereafter and hemodynamically stable, with a rate of vasopressor therapy of 93.9 % (Table 3.6) The results of hemodynamic status were within the hemodynamic stability criteria for brain - dead liver donors of the 2007 Paris Organ Transplantation Conference, demonstrating that brain death resuscitation was effective in maintaining hemodynamic maintenance of donors The rate of hypothermia was 40.8 %, but the average temperature was kept constant during resuscitation, the difference between the times was not statistically significant (Table 3.6) The result of diabetes insipidus was 63.3%, similar in Seyed et al's study (70.2%) 4.2.2 Paraclinical characteristics 4.2.2.1 Donor hematology test results Liver donors had the highest percentage of blood group O (55.1%), the lowest is blood group AB, the reason is that blood group O is the easiest to donate The lowest average Hemoglobin index was 105.7 g/L (Table 3.7), which was an indicator that ensures the goal of resuscitation (hemoglobin >70 g/L) to help maintain organ function 57.1% of patients required transfusion of red blood cells with the amount of 1026.79 ± 604.69 ml The mean of red blood cells and hemoglobin still decreased significantly over time (p = 0.049; 0.014 respectively) (Table 3.7), showing that the anemia of brain-dead patients always ... decades However, the transplant field has always faced the problem of scarcity of donated organs for all organs and especially the liver Liver from brain-dead donors is the most common form, times... post-transplant outcomes The organ procurement procedure is also the key to having a good graft both anatomically and functionally Any technical mistakes can lead to irreversible organ damage In Vietnam,... exploration; vascular preparation; refrigeration and organ removal In the braindead donor, the liver is taken mainly in the multiple organs In the step of vascular preparation, there are two