Donation after circulatory death heart transplant.
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ABSTRACT:
SUBMITTER: Yadava OP
PROVIDER: S-EPMC7538526 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDonation after circulatory death (DCD) hearts requires machine perfusion preservation, the conditions of which are not well defined.MethodsTo achieve this, rat hearts were procured following a DCD or control beating-heart donation (CBD) model, and perfused for 60 min with one of three machine perfusion solutions-St. Thomas (ST), University of Wisconsin (UW), or Polyethylene Glycol-20k (PEG)-at one of two temperatures, 4°C or 15°C. At 15-min intervals, perfusion pressure was measured as a marker of vascular resistance. Colored microspheres were added to capture the distribution of perfusate into the metabolically active sub-endocardium, and the eluate was collected for troponin assays. Analyses compared groups using Wilcoxon rank-sum and ANOVA.ResultsPerfusion pressure was significantly higher for DCD than CBD hearts at 15°C regardless of solutions. The lowest rise in perfusion pressure over time was observed with PEG at 15°C. Except for PEG at 15°C, ST and UW solutions at 4 or 15°C had decreased sub-endocardial perfusion in DCD hearts. Troponin release from DCD hearts with UW and PEG solutions was comparable to CBD hearts but was significantly higher with ST solution at 15°C.ConclusionsOptimal preservation conditions for DCD hearts were observed with PEG machine perfusion solution at 15°C.
| S-EPMC9307000 | biostudies-literature
Project description:RATIONALE:To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). OBJECTIVES:To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. METHODS:After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS:Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant. CONCLUSIONS:The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool. CLINICAL TRIAL REGISTRATION:NCT01615484.
| S-EPMC5711345 | biostudies-literature
Project description:In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors.
| S-EPMC5491386 | biostudies-literature
Project description: Not available
| S-EPMC5492185 | biostudies-literature
Project description:Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient's hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)-perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available-patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.
| S-EPMC8662509 | biostudies-literature
Project description:PurposeHeart donation and transplantation following circulatory determination of death has yet to be performed in Canada. A consensus forum was held to provide expert guidance to inform policy with a comprehensive patient partner strategy. This paper describes the process used to create fulsome patient partner engagement resulting in mutually beneficial policy development in this complex area.MethodsA wide-ranging process for involving patient partners in this area included pre-meeting education, in-meeting expert support, full participation and permission to step back if desired, and post-meeting debriefing. Following the meeting, a questionnaire was used to guide a debrief discussion with patient partners and steering committee members who co-authored this paper.ResultsFive key themes arose that echoed the sentiments and contributions made by patient partners, including: 1) a strong desire to improve the system, 2) gratitude and honour, 3) expert support and process, 4) simplification of complex concepts, and 5) mutual benefit expressed by patient partners and healthcare professionals.ConclusionDespite the complexity of the content and the emotionally sensitive nature of discussions around deceased organ donation, a well-planned strategy to involve patient partners is important, impactful, and central to the process. This suggests a broad interprofessional audience can engage with properly prepared and supported patient partners to strengthen and focus dialogue and outputs in the development of health policy in the donation and transplant sector.
| S-EPMC7716912 | biostudies-literature
Project description: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.
| S-EPMC8035095 | biostudies-literature
Project description:ObjectiveDespite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse.MethodsAll donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use.ResultsA total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO2/FiO2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO2/FiO2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001).ConclusionsNontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool.
| S-EPMC7647952 | biostudies-literature
Project description:While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (N = 15) who had direct experience with unsuccessful DCD and 5 focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize the harms of nondonation as perceived by participants. Participants reported a broad spectrum of harms affecting organ recipients, donors, and donor families. Harms included waste of precious life-giving organs and hospital resources, inability to honor the donor's memory and character, and impaired ability for families to make sense of tragedy and cope with loss. Donor families empathized with the initial hope and ultimate despair of potential recipients who must continue their wait on the transplant list. Focus group members reinforced these findings and highlighted the struggle of families to navigate the uncertainty regarding the timing of death during the donation process. While families reported significant harm, many appreciated the donation attempt. These findings highlight the importance of organ donation to donor families and the difficult experiences associated with current processes that could inform development of alternative donation strategies.
| S-EPMC5790593 | biostudies-literature
Project description:Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia-reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer's acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.
| S-EPMC10774377 | biostudies-literature