Heart donation and transplantation after circulatory determination of death: expert guidance from a Canadian consensus building process.

Controlled donation after circulatory determination of death (DCD), where death is determined after cardiac arrest, has been responsible for the largest quantitative increase in Canadian organ donation and transplants, but not for heart transplants. Innovative international advances in DCD heart transplantation include direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). After death is determined, DPP involves removal and reanimation of the arrested heart on an ex situ organ perfusion system. Normothermic regional perfusion involves surgically interrupting (ligating the aortic arch vessels) brain blood flow after death determination, followed by restarting the heart and circulation in situ using extracorporeal membrane oxygenation. The objectives of this Canadian consensus building process by a multidisciplinary group of Canadian stakeholders were to review current evidence and international DCD heart experience, comparatively evaluate international protocols with existing Canadian medical, legal, and ethical practices, and to discuss implementation barriers. Review of current evidence and international experience of DCD heart donation (DPP and NRP) determined that DCD heart donation could be used to provide opportunities for more heart transplants in Canada, saving additional lives. Although candid discussion identified a number of potential barriers and challenges for implementing DCD heart donation in Canada, it was determined that DPP implementation is feasible (pending regulatory approval for the use of an ex situ perfusion device in humans) and in alignment with current medical guidelines for DCD. Nevertheless, further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

RéSUMé: Le don contrôlé après un décès circulatoire (DDC), cas dans lequel le décès est déterminé après un arrêt cardiaque, est à l'origine de la plus forte augmentation quantitative des dons et des transplantations d'organes au Canada, sauf pour les transplantations cardiaques. Parmi les progrès internationaux novateurs dans la transplantation cardiaque après DDC, citons l'obtention directe et perfusion (ODP) et la circulation régionale normothermique (CRN). Une fois le décès déterminé, l'ODP consiste à retirer et réanimer le cœur arrêté sur un système de perfusion ex situ. La circulation régionale normothermique consiste à interrompre de manière chirurgicale (en ligaturant les vaisseaux de l'arc aortique) le flux sanguin au cerveau après la détermination du décès, puis à redémarrer le cœur et la circulation in situ utilisant l'oxygénation par membrane extracorporelle (ECMO). Les objectifs de ce processus canadien d'établissement de consensus par un groupe multidisciplinaire d'intervenants canadiens étaient d'examiner les données probantes et les expériences internationales actuelles en matière de DDC, d'évaluer comparativement les protocoles internationaux par rapport aux pratiques médicales, juridiques et éthiques canadiennes existantes, et de discuter des obstacles à la mise en œuvre de tels protocoles. L'examen des données probantes et des expériences internationales actuelles en matière de don de cœur après DDC (ODP et CRN) a permis de déterminer que le don de cœur après DDC pourrait être utilisé afin de faire de plus nombreuses transplantations cardiaques au Canada, sauvant ainsi des vies supplémentaires. Bien que des discussions aient permis d'identifier plusieurs obstacles et défis potentiels à la mise en œuvre du don cardiaque après DDC au Canada, il a été déterminé que la mise en œuvre de l'ODP est réalisable (en attente de l'approbation réglementaire pour l'utilisation d'un dispositif de perfusion ex situ chez l'humain) et en accord avec les directives médicales actuelles concernant le DDC. Néanmoins, d'autres travaux sont nécessaires pour évaluer la conformité de la CRN aux politiques canadiennes actuelles de détermination de la mort et pour garantir l'absence de perfusion cérébrale au cours de ce processus.

Lung donation after medical assistance in dying at home.

Organ donation after medical assistance in dying (MAID) has only been possible for patients having the MAID procedure performed at a hospital facility due to prohibitive warm ischemic times. Herein, we describe a protocol for lung donation following MAID at home and demonstrate excellent postoperative outcomes. Lung donation following MAID at home is possible and should be considered by transplant programs.

Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposal.

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.

Development of a national minimum data set to monitor deceased organ donation performance in Canada.

PURPOSE: Deceased donation data requires standardization to enable accurate interprovincial and international comparisons of deceased donation performance. In Canada, most provincial organ donation organizations (ODOs) have developed different processes and infrastructures for referring potential donors and subsequent data collection. This has led to differing definitions of the performance measures used for each step in the donation process, from potential donor identification to consent to transplantation. The Deceased Donation Data Working Group (DDDWG), comprised of representatives from ODOs across Canada, was therefore convened by Canadian Blood Services to develop a national, comprehensive, standardized deceased donation minimum data set. METHODS: The DDDWG's scope encompassed considering all potential deceased organ donation data elements, including operational and performance data collected along the deceased donor pathway from donation potential to donation and disposition of organs. An environmental scan was conducted of other existing deceased donation registries from the Canadian and the international community. The DDDWG then engaged in regular face-to-face meetings and teleconferences to develop recommendations for the minimum data set that would satisfy key considerations, including the impact on existing ODO data collection processes, financial impact on stakeholders, the clinical and operational needs of multiple healthcare professionals involved in the deceased donation pathway, and availability of other existing national data sets that could be leveraged to reduce data collection burden. RESULTS: The key deceased donation data elements identified by the DDDWG are contained in an inverted pyramid framework that was derived from similar work conducted in other countries. CONCLUSION: The DDDWG developed recommendations for proposed definitions and data sources that should be adopted nationally to guide the collection of deceased donation data. The ultimate purpose of the final minimum data set is to harmonize and standardize donation data definitions in Canada and align with international standards; inform the development of operational and clinical practice standards at the provincial and national levels; develop a framework for deceased donation performance measures; and advance the science of deceased donation.

RéSUMé: OBJECTIF: Les données concernant les dons d'organes de personnes décédées doivent être normalisées pour permettre des comparaisons précises de l'efficacité de ces dons entre provinces et entre pays. Au Canada, la majorité des organismes provinciaux de dons d'organes (ODO) ont élaboré divers processus et infrastructures pour l'orientation des donneurs potentiels et la collecte subséquente des données. Cela a abouti à des définitions différentes des mesures de performances utilisées pour chaque étape du processus de don, de l'identification du donneur potentiel au consentement à la transplantation. Le Groupe de travail sur les données de donneurs décédés (DDDWG), constitué de représentants des ODO de tout le Canada a donc été réuni par la Société canadienne du sang (SCS) pour élaborer un ensemble national et complet de données minimums standardisées de dons d'organes de personnes décédées. MéTHODES: Le DDDWG avait pour mission d'envisager tous les éléments de données de dons d'organes potentiels de personnes décédées, y compris les données opérationnelles et de performance collectées le long du parcours du donneur décédé, depuis le don potentiel jusqu'à l'utilisation des organes. Une analyse environnementale des autres registres existants (canadiens et internationaux) de dons d'organes de personnes décédées a été effectuée. Le DDDWG a alors entrepris des entretiens en face à face et des téléconférences pour élaborer ses recommandations pour un ensemble minimum de données qui répondraient aux problèmes clés, y compris : leur impact sur les processus de collecte de données des ODO existants, l'impact financier pour les différents acteurs, les besoins cliniques et opérationnels des multiples professionnels de santé impliqués tout au long du parcours de don de la personne décédée, et la disponibilité d'autres ensembles de données qui pourraient être utilisés pour réduire le fardeau de la collecte des données. RéSULTATS: Les principales données de don d'organes de donneur décédé, identifiées par le DDDWG, tiennent dans un cadre en pyramide inversée tiré d'un travail semblable mené dans d'autres pays. CONCLUSION: Le DDDWG a élaboré des recommandations pour les définitions proposées et les sources de données qui devraient être adoptées à l'échelon national pour guider la collecte des données de dons d'organes de personnes décédées. Le but ultime de l'ensemble minimum final de données est d'harmoniser et standardiser les définitions des données concernant les dons au Canada et de s'aligner sur les normes internationales; d'informer le développement de normes opérationnelles et de pratique clinique au niveau des provinces et au niveau national; de développer un cadre pour la mesure des performances concernant les dons de donneurs décédés; et de faire progresser les connaissances sur ce type de dons.

Familial Consent for Deceased Organ Donation Among Immigrants and Long-term Residents in Ontario, Canada: A Population-Based Retrospective Cohort Study.

BACKGROUND: Many families choose not to consent to organ donation at the time of their loved one's death. In Ontario, Canada, whether these decisions vary by ethnicity remains unclear. OBJECTIVE: To compare the proportion of families of immigrants who consented for deceased organ donation with families of long-term residents. DESIGN: Population-based retrospective cohort study. SETTING: Potential donors in Ontario, Canada, between November 2008 and March 2013. METHODS: We used linked administrative databases to study the proportion of families who consented for deceased organ donation. RESULTS: Overall, of the 2873 families of potential donors approached, 1912 (67%) provided consent for deceased organ donation. Families of immigrants were less likely to provide consent compared with families of long-term residents (46% [135 of 291] vs 69% [1777 of 2582]; adjusted rate ratio (RR): 0.72; 95% confidence interval [CI]: 0.63-0.81). When examined by the country of birth, families of immigrants from the following regions were less likely to consent to organ donation compared with long-term residents: South Asia (RR: 0.71; 95% CI: 0.55-0.91), East Asia and Pacific (RR: 0.68; 95% CI: 0.53-0.88) and Middle East, North Africa, and sub-Saharan Africa (RR: 0.58; 95% CI: 0.37-0.91). LIMITATIONS: We could not determine why consent was not obtained. We had a small sample of immigrants. We only had access to the potential donors' information and not the family member who was approached for consent. Many characteristics that we examined were nonmodifiable (eg, age, sex). CONCLUSIONS: In Ontario, families of immigrants are less likely to consent to deceased organ donation. There is an opportunity to better understand the reasons for lower consent among certain immigrant groups.

CONTEXTE: À la mort d'un être cher, plusieurs familles refusent de consentir au don d'organes. Au Canada, particulièrement dans la province de l'Ontario, il demeure difficile d'établir si une telle décision varie selon l'origine ethnique des personnes concernées. OBJECTIF DE L'ÉTUDE: L'étude visait à comparer la proportion de familles issues de l'immigration ayant consenti au don d'organe après le décès d'un proche à celle de familles résidant au pays depuis longtemps. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective basée sur une population. CADRE DE L'ÉTUDE: On a ciblé les familles résidant en Ontario, au Canada, qui avaient été abordées entre septembre 2008 et mars 2013 en vue de faire don des organes et des tissus d'un proche décédé. MÉTHODOLOGIE: Nous avons utilisé les bases de données couplées du système de santé pour établir la proportion de familles ayant consenti au don d'organes d'un proche décédé. RÉSULTAT: Dans l'ensemble, la majorité des 2 873 familles abordées, soit 1 912 (67 %), a consenti au don d'organes de leur proche décédé. Nous avons toutefois constaté que les familles issues de l'immigration se sont montrées plus réticentes à consentir au don d'organes que les familles de résidents de longue date (46 % [135 of 291] contre 69 % [1777 of 2582]; RR à 0,72 %; IC 95 % : 0,63 à 0,81). La comparaison sur la base du pays d'origine a permis d'établir que les personnes en provenance des régions suivantes étaient plus susceptibles de refuser de donner leur consentement : Asie du Sud (RR à 0,71; IC 95 % : 0,55 à 0,91), Asie de l'Est et du Pacifique (RR à 0,68; IC 95 % : 0,53 to 0,88), Moyen-Orient, Afrique du Nord et Afrique subsaharienne (RR à 0,58; IC 95 % : 0,37 to 0,91). LIMITES: La portée des résultats de cette étude pourrait être limitée par plusieurs facteurs : notamment, nous n'avons pas pu obtenir d'information sur les raisons du refus de consentement, nous n'avions accès qu'aux renseignements du donneur potentiel et non à ceux des membres de la famille abordés pour la demande de consentement. Ajoutons à cela la taille restreinte de l'échantillon des familles issues de l'immigration et le fait que plusieurs des caractéristiques examinées n'étaient pas modifiables (l'âge ou le sexe, par exemple). CONCLUSION: Cette étude conclut qu'en Ontario, les familles issues de l'immigration sont plus réticentes à consentir au don d'organes et de tissus d'un proche décédé. Dès lors, une occasion nous est offerte pour tenter de mieux comprendre les raisons qui expliquent cette faible proportion de consentement chez certains groupes d'immigrants.

Effect of organ donation after circulatory determination of death on number of organ transplants from donors with neurologic determination of death.

BACKGROUND: To increase the available pool of organ donors, Ontario introduced donation after circulatory determination of death (DCD) in 2006. Other jurisdictions have reported a decrease in donations involving neurologic determination of death (NDD) after implementation of DCD, with a drop in organ yield and quality. In this study, we examined the effect of DCD on overall transplant activity in Ontario. METHODS: We examined deceased donor and organ transplant activity during 3 distinct 4-year eras: pre-DCD (2002/03 to 2005/06), early DCD (2006/07 to 2009/10) and recent DCD (2010/11 to 2013/14). We compared these donor groups by categorical characteristics. RESULTS: Donation increased by 57%, from 578 donors in the pre-DCD era to 905 donors in the recent DCD era, with a 21% proportion (190/905) of DCD donors in the recent DCD era. However, overall NDD donation also increased. The mean length of hospital stay before declaration for NDD was 2.7 days versus 6.0 days before withdrawal of life support and subsequent asystole in cases of DCD. The average organ yield was 3.73 with NDD donation versus 2.58 with DCD (p < 0.001). Apart from hearts, all organs from DCD donors were successfully transplanted. From the pre-DCD era to the recent DCD era, transplant activity in each era increased for all solid-organ recipients, including heart (from 158 to 216), kidney (from 821 to 1321), liver (from 477 to 657) and lung (from 160 to 305). INTERPRETATION: Implementation of DCD in Ontario led to increased transplant activity for all solid-organ recipients. There was no evidence that the use of DCD was pre-empting potential NDD donation. In contrast to groups receiving other organs, heart transplant candidates have not yet benefited from DCD.

Deceased Organ Donation Registration and Familial Consent among Chinese and South Asians in Ontario, Canada.

OBJECTIVE: For various reasons, people of Chinese (China, Hong Kong or Taiwan) and South Asian (Indian subcontinent) ancestry (the two largest ethnic minority groups in Ontario, Canada) may be less likely to register for deceased organ donation than the general public, and their families may be less likely to consent for deceased organ donation at the time of death. METHODS: We conducted two population-based studies: (1) a cross-sectional study of deceased organ donor registration as of May 2013, and (2) a cohort study of the steps in proceeding with deceased organ donation for patients who died in hospital from October 2008 to December 2012. RESULTS: A total of 49 938 of 559 714 Chinese individuals (8.9%) and 47 774 of 374 291 South Asians (12.8%) were registered for deceased organ donation, proportions lower than the general public (2 676 260 of 10 548 249 (25.4%). Among the 168 703 Ontarians who died in a hospital, the families of 33 of 81 Chinese (40.1%; 95% CI: 30.7%-51.6%) and 39 of 72 South Asian individuals (54.2%; 95% CI: 42.7-65.2%) consented for deceased organ donation, proportions lower than the general public (68.3%; 95% CI: 66.4%-70.0%). CONCLUSIONS: In Ontario, Canada Chinese and South Asian individuals are less likely to register and their families are less likely to consent to deceased organ donation compared to the remaining general public. There is an opportunity to build support for organ and tissue donation in these two large ethnic communities in Canada.

Piecewise disassembly of a large-herbivore community across a rainfall gradient: the UHURU experiment.

Large mammalian herbivores (LMH) strongly influence plant communities, and these effects can propagate indirectly throughout food webs. Most existing large-scale manipulations of LMH presence/absence consist of a single exclusion treatment, and few are replicated across environmental gradients. Thus, important questions remain about the functional roles of different LMH, and how these roles depend on abiotic context. In September 2008, we constructed a series of 1-ha herbivore-exclusion plots across a 20-km rainfall gradient in central Kenya. Dubbed "UHURU" (Ungulate Herbivory Under Rainfall Uncertainty), this experiment aims to illuminate the ecological effects of three size classes of LMH, and how rainfall regimes shape the direction and magnitude of these effects. UHURU consists of four treatments: total-exclusion (all ungulate herbivores), mesoherbivore-exclusion (LMH >120-cm tall), megaherbivore-exclusion (elephants and giraffes), and unfenced open plots. Each treatment is replicated three times at three locations ("sites") along the rainfall gradient: low (440 mm/year), intermediate (580 mm/year), and high (640 mm/year). There was limited variation across sites in soil attributes and LMH activity levels. Understory-plant cover was greater in plots without mesoherbivores, but did not respond strongly to the exclusion of megaherbivores, or to the additional exclusion of dik-dik and warthog. Eleven of the thirteen understory plant species that responded significantly to exclusion treatment were more common in exclusion plots than open ones. Significant interactions between site and treatment on plant communities, although uncommon, suggested that differences between treatments may be greater at sites with lower rainfall. Browsers reduced densities of several common overstory species, along with growth rates of the three dominant Acacia species. Small-mammal densities were 2-3 times greater in total-exclusion than in open plots at all sites. Although we expect patterns to become clearer with time, results from 2008-2012 show that the effects of excluding successively smaller-bodied subsets of the LMH community are generally non-additive for a given response variable, and inconsistent across response variables, indicating that the different LMH size classes are not functionally redundant. Several response variables showed significant treatment-by-site interactions, suggesting that the nature of plant-herbivore interactions can vary across restricted spatial scales.

Cryptic herbivores mediate the strength and form of ungulate impacts on a long-lived savanna tree.

Plant populations are regulated by a diverse array of herbivores that impose demographic filters throughout their life cycle. Few studies, however, simultaneously quantify the impacts of multiple herbivore guilds on the lifetime performance or population growth rate of plants. In African savannas, large ungulates (such as elephants) are widely regarded as important drivers of woody plant population dynamics, while the potential impacts of smaller, more cryptic herbivores (such as rodents) have largely been ignored. We combined a large-scale ungulate exclusion experiment with a five-year manipulation of rodent densities to quantify the impacts of three herbivore guilds (wild ungulates, domestic cattle, and rodents) on all life stages of a widespread savanna tree. We utilized demographic modeling to reveal the overall role of each guild in regulating tree population dynamics, and to elucidate the importance of different demographic hurdles in driving population growth under contrasting consumer communities. We found that wild ungulates dramatically reduced population growth, shifting the population trajectory from increase to decline, but that the mechanisms driving these effects were strongly mediated by rodents. The impact of wild ungulates on population growth was predominantly driven by their negative effect on tree reproduction when rodents were excluded, and on adult tree survival when rodents were present. By limiting seedling survival, rodents also reduced population growth; however, this effect was strongly dampened where wild ungulates were present. We suggest that these complex interactions between disparate consumer guilds can have important consequences for the population demography of long-lived species, and that the effects of a single consumer group are often likely to vary dramatically depending on the larger community in which interactions are embedded.