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Lung Donation After Circulatory Death

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Lung Donation After Circulatory Death 10 Review Article Page 1 of 10 Lung donation after circulatory death Valeria Musso1,2, Ilaria Righi1, Francesco Damarco1, Alessandra Mazzucco1,2, Alberto Zanella2,3, Luigi Vivona2, Alessandro Palleschi1,2 1Thoracic Surgery and Lung Transplantation Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico of Milan, Milan, Italy; 2Università degli Studi di Milano, Milan, Italy; 3Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico of Milan, Milan, Italy Contributions: (I) Conception and design: A Palleschi, V Musso; (II) Administrative support: A Palleschi; (III) Provision of study materials or patients: A Palleschi, V Musso, F Damarco, A Zanella; (IV) Collection and assembly of data: A Palleschi, V Musso, F Damarco, A Mazzucco, L Vivona; (V) Data analysis and interpretation: A Palleschi, V Musso, I Righi; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Valeria Musso. Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico of Milan, Via Francesco Sforza 35, Milan, Italy. Email: [email protected]. Abstract: Donation after circulatory death (DCD) defines organs procurement after death determined using circulatory criteria, as opposed to a declaration based on neurological criteria. Nowadays, DCD donors represent a valuable resource to contrast lung donor shortage and waiting list mortality, while also avoiding the potential lung damages generated by brain death. On the other hand, lungs from DCD donors are exposed to a variable warm ischemia time and related potential detrimental effects. The extensive experimental investigation proved the feasibility of this practice, and the subsequent clinical experiences around the world showed good outcomes. In this paper, we review the pre-clinical and clinical experiences in the DCD field, focusing on ischemia time and the biological peculiarities of the lung tissue in animal models. We illustrate the clinical paths of the DCD donor categories as described in the Maastricht classification, and the different preservation techniques and procurement protocols, with particular regard to the ethical and legal differences around the world. We analyse the characteristics of both the controlled and uncontrolled setting, highlighting the advantages and disadvantages of each donation setting. We then proceed to review the clinical outcomes as well as the complications after lung transplantation from DCD donors as reported in literature. Lastly, we outline the role of machine perfusion for the function assessment and reconditioning of grafts procured in this scenario. Keywords: Donation after circulatory death (DCD); transplantation; lung transplantation; uncontrolled DCD; controlled DCD Received: 02 September 2020; Accepted: 30 March 2021 doi: 10.21037/ccts-20-148 View this article at: http://dx.doi.org/10.21037/ccts-20-148 Introduction in order to act in accordance with the dead donor rule, as it happens for the donation after brain death (DBD) setting. Donation after circulatory death (DCD) defines organs The donor must already be dead before any vital organ is procurement from a donor whose death has been removed, and organ harvesting must not cause the donor’s determined using circulatory criteria, as opposed to death. The very first lung transplantation was performed a declaration based on neurological criteria. Death is with organs procured from a DCD donor (1). Only after ultimately assumed as the loss of brain function due to the the Harvard criteria were published, both the brain death prolonged absence of encephalic perfusion. In this situation, concept and the DBD path gained worldwide traction, the primum movens is an irreversible cardiac arrest with an in light of the encouraging clinical results (2). Interest in adequate period of asystole. These criteria are established DCD was renewed in the last 20 years thanks to Love’s © Current Challenges in Thoracic Surgery. All rights reserved. Curr Chall Thorac Surg 2021 | http://dx.doi.org/10.21037/ccts-20-148 Page 2 of 10 Current Challenges in Thoracic Surgery, 2021 Table 1 Maastricht DCD classification result in pulmonary oedema, and that prevention of alveolar Category Definition collapse via post-mortem pulmonary inflation protected the Uncontrolled I Death on arrival lungs from suffering warm ischemia time (WIT) injuries (7). To investigate the effects of donor prone positioning on Uncontrolled II Unsuccessful resuscitation lung preservation in DCD, the Toronto group used a Controlled III Awaiting cardiac arrest controlled DCD swine model. After death determination, Controlled IV Cardiac arrest while brain dead pigs remained supine or were positioned prone, ventilation was resumed for 5 minutes and the endotracheal tube was clamped after recruitment manoeuvres. After work and to Steen’s experiences in 2001 (3,4). Nowadays, 3 hours of WIT, 6 hours of cold preservation and 6 hours DCD donors represent a valuable resource to contrast the of normothermic machine perfusion, the results show a long-standing problems of lung donor shortage and waiting better tolerance to WIT, less atelectasis and apoptosis in list mortality. Moreover, the use of grafts from DCDs the prone positioned group. These results confirmed once helps to avoid the pro-inflammatory cytokines and the again the importance of ventilation in lung preservation (8). catecholamines ‘storms’ that occur after brain death, which Great interest has always been given to the intrapulmonary pose a significant threat to the lung rather than to the other thrombi formation after lung procurement from DCD and organs. On the other hand, lungs from DCDs are exposed subsequent reperfusion injury. The group from Leuven to warm ischemia and its potential damages. adopted four different approaches in a porcine DCD model: in one group, they administrated heparin post-mortem, for the second group in situ retrograde flushing with Perfadex Pre-clinical experiences solution was employed, for the third one they adopted a Pulmonary cells’ resistance to ischemia is well known as combined approach (heparinization and retrograde flushing) well as the possibility for them to dissociate ischemia from and the last one received no intervention (control group) (9). hypoxia by using the oxygen supplied from ventilation. In The lungs were procured and then assessed in an ex-vivo 1991, Egan published a study on the ability of lung cells to model and ventilation and vascular resistance parameters endure ischemia for an adequate period of time using a single were analysed. The retrograde flushing and the combined left lung transplant canine model, proving the feasibility approach group showed better results in terms of both types of procurement from non-heart-beating donors (5). of variables. The Lund group designed an experimental Lung harvesting was performed 1, 2 and 4 hours after the study on pigs to investigate the role of alteplase in addition donor’s death, and grafts were stored on ice for 4 hours to Perfadex during lung flushing in the prevention of lung before carrying out transplantation. The Authors claimed thrombosis (10). Grafts were then assessed via ex-vivo lung that lung retrieval from DCD donors was safe and effective. perfusion (EVLP). Lung functionality was excellent in all A few years later, studies on pulmonary cell injury after 12 cases; however, despite slightly better blood gases and cardiocirculatory arrest demonstrated that cell death was pulmonary vascular resistance in the alteplase group, the delayed by supplying oxygen via mechanical ventilation (6). difference between the two groups was not statistically The work of Van Raemdonck et al. further confirmed the significant. key role of ventilation in this scenario. Ventilation-related parameters, pulmonary vascular resistance and pulmonary Classification oedema were compared using a DCD rabbit model after delayed pulmonary flushing. The lungs received six different The term “DCD” encompasses clinical situations of great post-mortem protocols: immediate flushing (control DBD variety, hence the necessity to establish a classification group), lung deflation (control DCD group), inflation with of these donors. The most known and widely used is the room air, inflation with pure oxygen (fraction of inspired Maastricht classification, which was drafted in 1995 at the oxygen, FiO2=100%), ventilation with room air, ventilation First International Workshop on DCD (Table 1) (11). This with 100% nitrogen or ventilation with 100% oxygen. classification identifies two main classes: uncontrolled DCD Lungs in each group were flushed after different ischemic (uDCD) includes categories I and II, where the cardiac times to study the organ tolerance to ischemia. The Authors arrest is unanticipated and therefore the donor’s medical concluded that delayed lung flushing in deflated lungs could history is unknown. Category I donors are those found dead © Current Challenges in Thoracic Surgery. All rights reserved. Curr Chall Thorac Surg 2021 | http://dx.doi.org/10.21037/ccts-20-148 Current Challenges in Thoracic Surgery, 2021 Page 3 of 10 Table 2 DCD no touch period lengths in different countries net result is the development of a range of DCD programs, No touch period with different approaches, in a controlled or uncontrolled Country (minutes) setting, addressed to single or multiorgan procurement. 5 Belgium, France, The Netherlands, Spain, The main differences among protocols are related to the United Kingdom, USA required
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