Littérature scientifique sur le sujet « Controlled donation after circulatory death »

Donor organ shortage is a major barrier to the progress of liver transplantation; options to widen the donor pool include use of marginal donor grafts and those from donors after circulatory death (DCD), despite risks of early graft failure. This thesis studies the key metabolic feature differences between DCD and from donors after brain death (DBD), using combination of microdialysis for tissue fluid sampling, and colourimetry, Coularray and Fourier Transform ion Cyclotron Resistance - mass spectrometry(FTICR-MS) as analytical platforms. The initial study proved feasibility of above methods to identify metabolic changes through cold storage to reperfusion, and the involvement of energy and amino acid metabolism pathways. Comparison of DCD and DBD grafts by microdialysis combined with colourimetry proved energy depletion, and increased lactate/pyruvate ratio in DCD grafts. Metabolomic studies consolidated the findings of primary impact on energy metabolism pathways during cold storage. Both CEAD and FTICR-MS identified key biomarker differences and the effect on tryptophan and kynurenine pathway, and this finding was reproduced in all three metabolomic studies conducted. Over expression of these metabolites in DCD grafts and failed allografts may be related to energy metabolism, and tryptophan and kynurenine could potentially be developed as biomarkers predicting liver graft function.

Cardiac transplantation is the treatment of choice for eligible patients with advanced heart failure; however, it is limited by a critical shortage of suitable organs from traditional brain-dead donors. Organs donated following circulatory death (DCD) have been used to successfully expand the pool of organs available for kidney, liver, and lung transplantation; however, concerns regarding the severity of injury sustained by the heart following withdrawal of life sustaining therapy have deterred the clinical transplantation of DCD hearts. Investigations aiming to optimize the resuscitation, preservation, and evaluation of DCD hearts may facilitate the development of an evidence based protocol for DCD heart transplantation that can be translated to the clinical area and expand the donor pool. Therefore, the objectives of this thesis are to develop a clinically relevant large animal model of DCD and gain a greater understanding regarding the physiologic impact of donor extubation on the DCD heart, demonstrate as a ‘proof-of-concept’ that utilizing an approach to donor heart resuscitation, preservation, and evaluation that is tailored to the DCD context can facilitate successful transplantation, and finally to investigate ways to optimize the resuscitation, preservation, and evaluation of DCD hearts for transplantation. The results of this thesis may then be used to inform the development of an evidence-based protocol for DCD heart transplantation that can be translated to the clinical area. The clinical adoption of such a protocol has the potential to expand the donor pool and improve outcomes for patients with end-stage heart failure.
May 2017

Bakgrund: Över hela världen råder det brist på organ. 1 januari 2019 stod 807 personer på väntelistan för att få ett nytt organ i Sverige. Efterfrågan på organ är större än tillgången. Efterfrågan skulle kunna tillmötesgå bättre om DCD (eng. Donation after Circulatory Death) kan implementeras som ett komplement till DBD (eng. Donation after Brain Death). Det har pågått ett pilotprojekt på sex olika sjukhus i Sverige.Måletmed projektet var att utreda om DCD i framtiden kan vara ett komplement till den idag etablerade donationsprocessen DBD vilket leder till att sjukvården kan möta allmänhetens donationsvilja samt öka antalet organ för transplantation. Då DCD inte är nationellt implementerat och genom att intensivvårdssjuksköterskor har ansvaret för att vårda potentiella organdonatorer är det viktigt med forskning som belyser intensivvårdssjuksköterskorsresonemang och föreställningar kring DCD.Syfte:Syftet var att beskriva intensivvårdssjuksköterskors resonemang och föreställningar om donation vid kontrollerad DCD.Metod:Kvalitativ intervjustudie med ändamålsenligt urval genomfördes. Data analyserades med kvalitativ innehållsanalys.Resultat:Analysen resulterade i fyra kategorier; Att påbörja något nytt inom området donation, Att erhålla kunskap minskar farhågor och oro, Att införa donation efter cirkulationsstillestånd ger möjlighet att möta en hög donationsvilja och att informera och ge tröst till anhöriga.Slutsats: Denna studie visar att engagemanget är stort hos intensivvårdssjuksköterskor och att tilltron tillett införande av DCD är hög. Genom att införa DCD som ett komplement till DBD så skulle fler donationer kunna genomföras och på sikt kunna matcha efterfrågan på organ. Mer forskning samt utbildning behövs för att öka kunskapen utifrån de krav som kommer att ställas på intensivvårdssjuksköterskor vid en eventuell implementering av DCD.

Bakgrund: Organdonation kan rädda människors liv när all annan möjlig behandling redan testats. Behovet av organ i Sverige överskrider idag tillgången, vilket resulterar i att människor avlider i väntan på ett organ. Förutom att möjliggöra en människas överlevnad är transplantation mer kostnadseffektivt än kontinuerlig behandling. I nuläget finns inga nationella riktlinjer i Sverige för utbildning inom organdonation för intensivvårdssjuksköterskor. Forskning har visat att intensivvårdssjuksköterskans arbete är av stor vikt för donationsprocessen. Syfte: Syftet med studien är att belysa behovet av utbildning hos intensivvårdssjuksköterskor som vårdar potentiella avlidna donatorer. Metod: Studien har utförts genom en litteraturstudie med systematisk datainsamling. Integrativ metod med en kvalitativ innehållsanalys har använts då artiklar med både kvalitativ och kvantitativ ansats analyserats för att besvara syftet för studien. Resultat: En stor del intensivvårdssjuksköterskor upplevde sig vara obekväma med att vårda organdonatorer. Vårdandet av en donator kan medföra att mycket känslor uppstår hos intensivvårdssjuksköterskan och upplevdes som mentalt påfrestande. Utbildning inom organdonation kan hjälpa intensivvårdssjuksköterskan att hantera dessa känslor. Utbildning kan även leda till att fler potentiella donatorer identifieras. Utbildning behöver ges regelbundet och intensivvårdssjuksköterskan behöver specifikt utbildning om donationsprocessen, bemötande och kommunikation av de närstående samt skillnader i hjärt- och hjärndöda patienter. Slutsats: Intensivvårdssjuksköterskan behöver få en djupare förståelse av vården kring organdonation och få en ökad kunskap och utbildning för att stärka sin professionella roll. Utbildning kan även förbättra donationsprocessen och möjliggöra för fler donatorer. Vidare forskning inom området anses behövas för att utveckla vården kring donatorer och närstående.
Background: Organ donation can save lives when all other treatment options have been exhausted. Today, the demand for organs in Sweden exceeds supply, resulting in people dying in wait for an available organ for transplantation. In addition to saving a person’s life, transplantations are more cost-effective than continuous treatment. Currently, there are no national guidelines for the provision of training in the area of organ donations for intensive care nurses. Research has shown that the efforts of intensive care nurses play a major role in the donation process. Aim: The aim of this study is to shed light on the need for training of intensive care nurses caring for potential deceased donors. Methodology: The study was conducted through a literature review with systematic data collection. An integrative method with qualitative content analysis was employed, as articles with both qualitative and quantitative approaches were analysed to shed light on the aim of the study. Findings: A large proportion of intensive care nurses felt uncomfortable caring for organ donors. Caring for a donor can be a very emotional and mentally trying experience for intensive care nurses. Organ donation training can help intensive care nurses cope with these feelings. Training can also result in the identification of more potential donors. Regular training is necessary, and intensive care nurses require specific training on the donation process, treatment and communication with next of kin as well as differences between donation after cardiac death patients and donation after brain death patients. Conclusion: The intensive care nurses needs to gain a deeper understanding of the care surrounding organ donation. To increase the professional role of the nurse there is a need to strengthen the knowledge and education. The donation process could be improved by education, which can lead to more organ donations. Further research within this area of expertise needs to be done to be able to develop the care for the donors and their families.

碩士
國立臺灣大學
醫學教育暨生醫倫理研究所
104
Historically, the development of organ donation began with donation after circulatory death (DCD), followed by donation after brain death (DBD). Many countries reestablished DCD protocol due to the increasing gap between vital organs demand and supply in recent years. DCD became a focus of debates in the 2014 Taipei City mayor election. However, many criticisms of DCD were not intended for rational discussion and dialogue and have hurt the trust for organ donation in the society. The goals of this thesis are to invite a rational dialogue and repair the damaged social trust. The thesis emphasizes the following: First, to clarify the definition and content of DCD. The necessity to apply DCD in Taiwan was explored, considering history, supply and demand, and global trends. Second, to facilitate mutual dialogue in the society, the methods to implement inquiry and registry of the willingness for organ donation in the general public were discussed. Third, to fulfill the principle of respect for autonomy, additional options in the organ donation registration form were suggested. For example, would the patient accept death determination based on circulatory death criteria, kinds of organ the patient wish to donate, and would the patient accept interventions intended to improve organ quality in end-of-life care. Fourth, to explore the ethical issues arising from DCD, including the determination of death, how to avoid conflict of interests, and antemortem and postmortem interventions. Fifth, to explore if the practice of DCD is legal under current Taiwanese laws. Relevant U.K. and U.S.A. laws were compared to clarify the concepts. Finally, I argue that the implementation of DCD needs comprehensive laws and ethical norms, and Taiwanese society already possesses such potential for the introduction and practice of DCD now. We should make sure, however, that DCD be established on an open and transparent basis and performed in a stepwise and orderly way. Under the premise of respect for autonomy, further mutual dialogue is needed to rebuild social trust.

Introduction Liver transplantation is currently the only effective therapy for patients with end stage acute or chronic liver failure. The increasing request of organs has led to the more extensive use of the so-called marginal donors, in particular donors after circulatory death (DCD). Within this model of donation, a more severe degree of ischaemia-reperfusion injury (IRI) is occurring, that seems to play a role on the pathogenesis of local and remote organ complications. This research will focus on the influence of liver graft injury on the pathogenesis of local and remote organ complications, evidencing the role of IRI leading to biliary complications and development of systemic inflammatory response associated with the occurrence of acute kidney injury (AKI). Aim of the study was to assess the role of IRI in two different models of ischaemia, DCD and donation after brain death (DBD), in liver transplanted grafts, on the pathogenesis of local and remote organ complications. We evaluated the development of biliary complications and its association with the degree of donor liver graft bile duct injury after liver reperfusion. Moreover, the development of AKI after liver transplantation was considered, as consequence of IRI and systemic inflammatory response. Methods Retrospective single-centre study of adult patients who underwent liver transplantation at University Hospital Birmingham (UHB) National Health Service (NHS) Foundation Trust from January 2007 to December 2014. Characteristics of recipient at transplant, recipient renal and liver function in the immediate pre-transplant period, donor and graft variables, intra-operative parameters, indicators of initial graft function and renal function in the post-transplant period were considered. Primary end points were the occurrence of biliary complications, in particular ischaemic cholangiopathy (IC), and development of AKI. Secondary end point was the evaluation of IRI damage on the basis of transaminases, bilirubin and INR over the first week post-transplant and the appearance of bile duct retrieved after liver reperfusion on histological examination. Severity of donor bile duct injury was assessed and scored on the basis of biliary epithelial cell loss, mural stroma necrosis, inflammation, peribiliary vascular plexus (PVP) damage, arteriolonecrosis, thrombosis, periluminal and deep peribiliary glands (PBGs) damage. Cholangiocyte apoptosis in periluminal and deep PBGs was evaluated by quantitative terminal deoxy-nucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) analysis on bile duct sections. Cholangiocyte proliferation was studied in bile duct sections by PCNA immunohistochemical expression. Results One thousand and 60 liver transplant recipients (813 from DBD and 247 from DCD) were considered. Recipients from DCD had higher ALT and AST in the first 7 days after transplant, compared to DBD. The occurrence of biliary complications was higher in DCD liver transplant recipients (85/247; 34%) compared to DBD (166/813; 20%) (p<0.001), in particular IC incidence was significantly higher in DCD. The incidence of AKI was 59.3% (629/1060 recipients) and was significantly higher in DCD (160/247, 64.8%) compared to DBD (469/813, 57.7%) recipients (p=0.047). Sixty-two patients comparable with the entire cohort, had the bile duct sample available for histological evaluation. A significantly higher number of DCD patients presented necrosis >50% of the bile duct wall [DCD 14/28 (50%), DBD 9/34 (26.5%) p=0.056], PVP damage [DCD 8/28 (29%), DBD 3/34 (9%); p=0.053] and periluminal PBGs damage [DCD 20/28 (71%), DBD 14/34 (41%); p=0.016]. These features defined the occurrence of severe histological injury, that was significantly more frequent in DCD liver transplant patients [15/28 (53.6%)] compared to DBD [7/34 (20.6%)] (p=0.007). A significant increased apoptosis and decreased proliferation was evidenced in both periluminal (Tunel assay p=0.029; PCNA expression p=0.029) and deep PBGs (Tunel assay p=0.002; PCNA expression p=0.006) from bile duct sample with severe histological injury. Discussion A more severe degree of IRI is occurring within DCD, as evidenced by greater graft dysfunction and increasing peak perioperative transaminases, likely related to the added donor warm ischaemia time. The IRI seems to play a role on the pathogenesis of local and remote organ complications, evidencing the role exerted in DCD leading to biliary complications and development of systemic inflammatory response associated with the occurrence of AKI. This study also shows an early picture of microscopic damage at the level of the bile duct soon after reperfusion of liver graft during transplantation. Bile duct samples retrieved from DCD grafts expressed more severe injury at the histological level, as evidenced by the increased incidence of mural stroma necrosis, PBP damage and PBG damage, defining the new feature of severe histological injury. Bile ducts with severe histological injury showed increased apoptosis and reduced proliferation, as evaluated by Tunel assay and PCNA expression, both on periluminal and deep PBG cholangiocytes. The higher incidence of IC development in DCD strongly suggests a relation between the occurrence of severe histological injury and alteration in bile duct repair mechanisms, raising hypothesis to further evaluate those mechanisms leading to the development of bile duct non-anastomotic strictures.