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Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

ABSTRACT: 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.

SUBMITTER: Egan TM

PROVIDER: S-EPMC5491386 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

Egan T M TM Requard J J JJ

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20150414 8

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 reco ...[more]

PMID: 25873272

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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.

Project description:Background and objectivesThe broader use of combined expanded criteria donor and donation after circulatory death (ECD/DCD) kidneys may help expand the deceased donor pool. The purpose of our study was to evaluate discard rates of kidneys from ECD/DCD donors and factors associated with discard.Design, setting, participants, & measurementsECD/DCD donors and kidneys were evaluated from January 1, 2000 to March 31, 2011 using data from the Scientific Registry of Transplant Recipients. The kidney donor risk index was calculated for all ECD/DCD kidneys. Multivariable logistic regression models were used to determine risk factors for discarding both donor kidneys. The Kaplan-Meier product limit method and the log-rank statistic were used to assess the cumulative probability of graft failure for transplants from ECD/DCD donors where the mate kidney was discarded versus both kidneys were used.ResultsThere were 896 ECD/DCD donors comprising 1792 kidneys. Both kidneys were discarded in 44.5% of donors, whereas 51.0% of all available kidneys were discarded. The kidney donor risk index scores were higher among donors of discarded versus transplanted kidneys (median, 1.82; interquartile range, 1.60, 2.07 versus median, 1.67; interquartile range, 1.49, 1.87, respectively; P<0.001); however, the distributions showed considerable overlap. The adjusted odds ratios for discard were higher among donors who were older, diabetic, AB blood type, and hepatitis C positive. The cumulative probabilities of total graft failure at 1, 3, and 5 years were 17.3%, 36.5%, and 55.4% versus 13.8%, 24.7%, and 40.5% among kidneys from donors where only one versus both kidneys were transplanted, respectively (log rank P=0.04).ConclusionsOur study shows a significantly higher discard rate for ECD/DCD kidneys versus prior reports. Some discarded ECD/DCD kidneys may be acceptable for transplantation. Additional studies are needed to evaluate the factors that influence decision making around the use of ECD/DCD kidneys.

Project description:BACKGROUND:Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs. METHODS:We used Large White pigs weighing between 45 and 55 kg. After 30 minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4 hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure. RESULTS:Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3 l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4 hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit. CONCLUSIONS:Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management.

Dataset Information

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

Publications

Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

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