Donation After Cardiocirculatory Death Research Articles

P0334 - Kidney transplantation from Donation after Cardiocirculatory Death (DCD) after Extracorporeal Membrane Oxygenation (ECMO) – What can we say after 5 years of experience?

P0334 - Kidney transplantation from Donation after Cardiocirculatory Death (DCD) after Extracorporeal Membrane Oxygenation (ECMO) – What can we say after 5 years of experience?

965 - Kidney transplantation from donation after cardiocirculatory death (DCD) after extracorporeal membrane oxygenation (ECMO) – outcomes from a longitudinal assessment with three years of experience

965 - Kidney transplantation from donation after cardiocirculatory death (DCD) after extracorporeal membrane oxygenation (ECMO) – outcomes from a longitudinal assessment with three years of experience

Lung transplantation from donation after controlled cardiocirculatory death. Systematic review and meta-analysis.

The interest in donation after cardiocirculatory death (DCD) donors for lung transplantation (LT) has been recently rekindled due to lung allograft shortage. Clinical outcomes following DCD have proved satisfactory. The aim of this systematic review is to provide a thorough analysis of published experience regarding outcomes of LT after controlled DCD compared with donation after brain death (DBD) donors. We performed a literature search in Cochrane Database of Systematic Reviews, PubMed and Web of Science using the items "lung transplantation" AND "donation after circulatory death" on November 1, 2018. The full text of relevant articles was evaluated by two authors independently. Quality assessment was performed using the NIH protocol for case-control and case series studies. A pooled Odds ratio (OR) and mean differences with inverse variance weighting using DerSimonian-Laird random effect models were computed to account for between-trial variance (τ2). Of the 508 articles identified with our search, 9 regarding controlled donation after cardiac death (cDCD) were included in the systematic review, including 2973 patients (403 who received graft from DCD and 2570 who had DBD). Both 1-year survival and 2 and 3-grade primary graft dysfunction (PGD) were balanced between the two cohorts (OR = 1.00 and 1.03 respectively); OR for airway complications was 2.07 against cDCD. We also report an OR = 0.57 for chronic lung allograft dysfunction (CLAD) and an OR = 0.57 for 5-year survival against cDCD. Our meta-analysis shows no significant difference between recipients after cDCD or DBD regarding 1-year survival, PGD and 1-year freedom from CLAD. Airway complications and long-term survival were both related with transplantation after cDCD, but these statistical associations need further research.

Hypothermic Machine Perfusion as an Alternative to Biopsy Assessment in Transplantation of Kidneys Donated After Cardiocirculatory Death: A Pilot Study

BackgroundTransplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors. MethodsFrom January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski’s score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type. ResultsA total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome. ConclusionsHMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Among the 73DCD liver transplantation procedures performed, 70recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8patients (25%) in the early era and 1patient (3%) in the late era (p= 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p= 0.01). The warm ischemia time (27 v. 24min, p= 0.049) and functional warm ischemia time (21 v. 17min, p= 0.002) were significantly lower in the late era than the early era. We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.

Deceased organ donation activity and efficiency in Switzerland between 2008 and 2017: achievements and future challenges

BackgroundVarious actions have been taken during the last decade to increase the number of organs from deceased donors available for transplantation in Switzerland. This study provides an overview on key figures of the Swiss deceased organ donation and transplant activity between 2008 and 2017. In addition, it puts the evolution of the Swiss donation program’s efficiency in relation to the situation in the neighboring countries.MethodsThis study is an analysis of prospective registry data, covering the period from 1 January 2008 to 31 December 2017. It includes all actual deceased organ donors (ADD) in Switzerland. Donor data were extracted from the Swiss Organ Allocation System. The “donor conversion index” (DCI) methodology and data was used for the comparison of donation program efficiency in Switzerland, Germany, Austria, Italy and France.ResultsDuring the study period there were 1116 ADD in Switzerland. The number of ADD per year increased from 91 in 2008 to 145 in 2017 (+ 59%). The reintroduction of the donation after cardiocirculatory death (DCD) program in 2011 resulted in the growth of annual percentages of DCD donors, reaching a maximum of 27% in 2017. The total number of organs transplanted from ADD was 3763 (3.4 ± 1.5 transplants per donor on average). Of these, 48% were kidneys (n = 1814), 24% livers (n = 903), 12% lungs (n = 445), 9% hearts (n = 352) and 7% pancreata or pancreatic islets (n = 249). The donation program efficiency assessment showed an increase of the Swiss DCI from 1.6% in 2008 to 2.7% in 2017 (+ 69%). The most prominent efficiency growth was observed between 2012 and 2017. Even though Swiss donation efficiency increased during the study period, it remained below the DCI of the French and Austrian donation programs.ConclusionSwiss donation activity and efficiency grew during the last decade. The increased donation efficiency suggests that measures implemented so far were effective. The lower efficiency of the Swiss donation program, compared to the French and Austrian programs, may likely be explained by the lower consent rate in Switzerland. This issue should be addressed in order to achieve the goal of more organs available for transplantation.

Donors after cardiocirculatory death and lung transplantation.

The number of patients actively awaiting lung transplantation (LTx) is more than the number of suitable donor lungs. The percentage of lung retrieval rate is lower when compared to other solid organs. The use of lungs from donation after cardiocirculatory death (DCD) donors is one of the options to avoid organ shortage in LTx. After extensive experimental research, clinical application of DCD donation is becoming wider. The results from most of the centers show at least equal survival rate compared to donors from brain death. This review paper will summarize experimental background and clinical experience from DCD donors.

Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis

Lung transplantation (LTx) can extend life expectancy and enhance the quality of life for select patients with end-stage lung disease. In the setting of donor lung shortage and waiting list mortality, the interest in donation after cardiocirculatory death (DCD) is increasing. We performed a systematic review and meta-analysis to compare outcomes between DCD and conventional donation after brain death (DBD). PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were searched. We identified original research studies with 1-year post-transplant survival data involving >5 DCD transplants. We performed meta-analyses examining 1-year survival, primary graft dysfunction, and acute rejection after LTx. We identified 519 citations; 11 observational cohort studies met our inclusion criteria for systematic review, and 6 met our inclusion criteria for meta-analysis. There were no differences found in 1-year mortality after LTx between DCD and DBD cohorts in individual studies or in the meta-analysis (DCD [n = 271] vs DBD [n = 2,369], relative risk [RR] 0.88, 95% confidence interval [CI] 0.59-1.31, p = 0.52, I(2) = 0%). There was also no difference between DCD and DBD in a pooled analysis of 5 studies reporting on primary graft dysfunction (RR 1.09, 95% CI 0.68-1.73, p = 0.7, I(2) = 0%) and 4 studies reporting on acute rejection (RR 0.72, 95% CI 0.49-1.05, p = 0.09, I(2) = 0%). Survival after LTx from DCD is comparable to survival after LTx from DBD in observational cohort studies. DCD appears to be a safe and effective method to expand the donor pool.

Fourteen Years of Experience in Uncontrolled Organ Donation After Cardio-Circulatory Death

BackgroundSince 1999, a protocol for uncontrolled donation after cardio-circulatory death (DCD) has been carried out in our institution. We aimed at evaluating those 14 years of local experience. MethodsWe reviewed the charts of uncontrolled donors from 1999 till 2013. Potential donors with a no-flow period less than 30 minutes were considered. Kidneys were perfused by the use of a double balloon triple lumen catheter after at least a 2-minute period of no touch. We analyzed grafts outcome and warm and cold ischemia times. ResultsThirty-nine procedures were initiated: 19 were aborted because of family refusal (n = 7), medical reasons (n = 7), or canulation failures (n = 5) and 20 harvesting procedures were completed. Transplantation was considered for 35 kidneys (cold storage [n = 5] and hypothermic preservation system [n = 30]). The causes of withdrawal from transplantation were mostly macroscopic lesions (poor perfusion, macroscopic parenchyma or vascular lesions, or infectious risk). We transplanted 22 kidneys locally and 3 were shipped to another Eurotransplant center. Mean donor age was 40 ± 13 years. Among the 20 donors, 13 came from the emergency unit and 7 from the intensive care unit. Mean no-flow time for out-hospital management was 8.7 ± 3.6 minutes. Mean time of cardiopulmonary resuscitation was 71 ± 46 minutes. Mean cold ischemia time was 19 ± 5 hours. Primary nonfunction and delayed graft function occurred in 1 and 12 cases (4.5% and 54%), respectively. Graft survival was 86% at 1 year. Causes of graft loss during the entire follow-up were graft rejection (n = 3), ischemically damaged kidney (n = 2), and recurrence of focal segmental glomerulosclerosis (n = 1). ConclusionIn our experience, uncontrolled donors represent a valuable source of kidney grafts, with a prognosis of graft function and survival similar to the literature. To increase the number of available DCD organs, new techniques, such as the use of Normothermic ExtraCorporeal Membrane Oxygenation (NECMO), as well as improvement of recruitment of out of hospital potential donors have to be considered.

Ethically Informed Pragmatic Conditions for Organ Donation after Cardiocirculatory Death: Could They Assist in Policy Development?

The modern practice of organ donation after cardiocirculatory death (DCD) emerged in the 1990s as a response to the alarmingly wide gap between the number of transplantable organs available through organ donation after neurological death and the urgent organ transplantation needs of persons in end-organ failure. Various important ethical dimensions of DCD have been considered and debated by prominent organ donation/transplantation theorists and clinicians. In this article, consideration of some of these ethical elements provides a foundation for a proposed set of ethically informed, pragmatic conditions that could assist in the development of health policies to guide the practice of organ donation after cardiocirculatory death.

Right Ventricular Distension in Donor Hearts Following Cardiocirculatory Death: Implications for Post-Transplant Function

<h3>Purpose</h3> Donation after cardiocirculatory death (DCD) may expand the donor pool for heart transplantation; however, right ventricular (RV) dysfunction has been observed in resuscitated DCD hearts and the cause of this is not well understood. We sought to characterize changes in RV pressure and volume following withdrawal of life-sustaining therapy (WLST) in a large animal model of DCD. <h3>Methods and Materials</h3> Thirteen pigs were anesthetized and mechanically ventilated with room air. Mechanical ventilation was discontinued, hypoxic cardiac arrest ensued, and a 10-minute standoff period was observed. Changes in RV pressure and volume were monitored using a conductance catheter and magnetic resonance imaging (MRI). <h3>Results</h3> The arterial partial pressure of oxygen decreased rapidly and reached its nadir after 2 minutes (Figure 1). This corresponded with an increase in RV systolic pressure (baseline RVSP 24.1±0.9 vs. 35±2 mmHg, p<0.01), diastolic function (baseline dPdt_min −172±24 vs. −267±24 mmHg/s, p<0.01), and systolic function (baseline dPdt_max 254±32 vs. 378±32 mmHg/s, p=0.01) compared to baseline. Subsequent RV function progressively declined leading to an 18±6% (p<0.01) increase in RV end-diastolic volume and an increase in RV end diastolic pressure (baseline 4.2±0.5 vs. 7.3±0.4 mmHg, p<0.01). MRI confirmed an 18±12% increase in RV end diastolic volume compared to baseline. <h3>Conclusions</h3> Following WLST the RV experiences significant distension that may exacerbate myocardial injury. Assessment of RV function prior to transplantation of the DCD heart is essential, highlighting the need for an <i>ex vivo</i> perfusion device capable of biventricular functional assessment.

An International Analysis of Policy Shifts to Donation After Cardio-circulatory Death (DCD) and Their Effect on Deceased Organ Donation and Transplantation Rates

Introduction: During the past decade an increasing number of countries have adopted policies that emphasize donation after cardio-circulatory death (DCD) in an effort to address the widening gap between demand and supply of transplantable organs. An analysis of international donation activity between 1989-2010 identified 25 countries that reported regular DCD activity. This research reports the impact of policy shifts towards increasing DCD upon overall deceased organ donation rates (DD), donation after brain death rates (DBD) and organ transplantation rates. Methods: Donor and transplant data was collected from multiple international donation and transplantation agencies and supplemented and cross-checked against responses to questionnaires sent to relevant national organ donor and transplant related bodies. Data was analyzed to determine correlations and associations between; DCD (both uncontrolled - Maastricht Class 1 & 2 (uDCD) and controlled Maastricht Class 3 & 4 (cDCD)); DBD; overall DD; and organ transplantation rates, with p = 0.05 considered significant. Results: Our results show that high national DD rates (> 20 DD pmp per year) were strongly associated with high DBD rates. In contrast, high DCD rates negatively impacted on a country's overall DD rate. In addition, there was a significant negative correlation (p = 0.0002) between DCD and DBD rates in countries with policies that resulted in high DCD rates. Finally, international data demonstrates that the total number of organs transplanted per donor is reduced by a factor of 1.5 in DCD when compared to DBD (p < 0.0001).Figure: [DCD Effect on DBD Rates]Figure: [Transplanted Organs per DCD & DBD Donor]Conclusion: While policies focused on uDCD may increase overall DD rates, increases in DD from policies that focus on cDCD come at the expense of DBD. We conclude that cDCD negatively impacts the number of donations from brain dead donors and may lead to an overall reduction in the number of transplants performed due to reduced organ retrieval rates.

Abstract 255: A Normokalemic Nondepolarizing Cardioplegia Minimizes Myocardial Injury and Improves Cardiac Function in a Large Animal Model of Donation After Cardiocirculatory Death

Background: Procurement of donor hearts is typically preceded by delivery of a cold hyperkalemic cardioplegia (CP) that achieves arrest by depolarization of the membrane potential. This method has no intrinsic cardioprotective properties and may exacerbate ischemia-reperfusion (IR) injury. A tepid adenosine-lidocaine (AL) non-depolarizing CP has been shown to limit IR injury and improve myocardial functional recovery in a small animal model of orthotopic heart transplantation. We sought to determine the impact of AL CP on myocardial injury and function, in a porcine model of donation after cardio-circulatory death (DCD). Methods: Female Yorkshire pigs (60 kg) were subjected to a hypoxic cardiac arrest. Following a 15-minute standoff period donor hearts were procured, resuscitated ex-vivo, and transplanted into a recipient animal. Hearts in group 1 (N=7) were protected with a cold blood-Plegisol CP, perfused with a blood-crystalloid solution during ex-vivo assessment, and arrested with a cold blood-Plegisol CP prior to transplantation. Hearts in group 2 (N=5) were protected with a tepid AL-STEEN CP and perfused with a blood-STEEN solution in a continuous fashion during ex-vivo assessment and transplantation. Results: Animals in group 2 had a significantly longer ex-vivo perfusion time compared to those in group 1 (174±29 vs. 135±45 min, p&lt;0.05), yet they demonstrated significantly less weight gain (14±4 vs. 25±8 grams/hour, p&lt;0.05). Further, animals in group 2 exhibited less troponin I release during ex-vivo perfusion and had significantly better diastolic function following wean from cardiopulmonary bypass (left ventricular end-diastolic pressure volume relationship 0.115±0.052 vs. 0.508±0.223, p&lt;0.05). However, there was no significant difference in level of calpain activity between groups (171.3±68.6 vs. 140.12±50.6, p=0.36). Conclusion: A tepid non-depolarizing AL CP results in less myocardial edema during ex-vivo perfusion, minimizes myocardial injury, and improves diastolic function following transplantation of DCD hearts, but fails to eliminate the activation of calcium-dependent proteases. Further studies should investigate if a calpain inhibitor delivered at reperfusion could further minimize IR injury in DCD hearts.

Categories of Donation After Cardiocirculatory Death

The interest in donation after cardiocirculatory death (DCD) was renewed in the early 1990s, as a means to partially overcome the shortage of donations after brain death. In some European countries and in the United States, DCD has become an increasingly frequent procedure over the last decade. To improve the results of DCD transplantation, it is important to compare practices, experiences, and results of various teams involved in this field. It is therefore crucial to accurately define the different types of DCD. However, in the literature, various DCD terminologies and classifications have been used, rendering it difficult to compare reported experiences. The authors have presented herein an overview of the various DCD descriptions in the literature, and have proposed an adapted DCD classification to better define the DCD processes, seeking to provide a better tool to compare the results of published reports and to improve current practices. This modified classification may be modified in the future according to ongoing experiences in this field.

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.

Results of kidney transplantation from controlled donors after cardio-circulatory death: a single center experience

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival, and post-transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end-points. This is a retrospective mono-center review of a consecutive series of 59 DCD-KT performed between 2005 and 2010. Overall graft survival was 96.6%, 94.6%, and 90.7% at 3 months, 1 and 3 years, respectively. Main cause of graft loss was patient's death with a functioning graft. No primary nonfunction grafts. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 45.6% of all DCD-KT. DGF significantly increased postoperative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index ≥30 was the only donor factor that was found to significantly increase the risk of DGF (P < 0.05). Despite a higher rate of DGF, controlled DCD-KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid-term results to those procured after brain death.

Donation after cardiocirculatory death: a call for a moratorium pending full public disclosure and fully informed consent

Many believe that the ethical problems of donation after cardiocirculatory death (DCD) have been "worked out" and that it is unclear why DCD should be resisted. In this paper we will argue that DCD donors may not yet be dead, and therefore that organ donation during DCD may violate the dead donor rule. We first present a description of the process of DCD and the standard ethical rationale for the practice. We then present our concerns with DCD, including the following: irreversibility of absent circulation has not occurred and the many attempts to claim it has have all failed; conflicts of interest at all steps in the DCD process, including the decision to withdraw life support before DCD, are simply unavoidable; potentially harmful premortem interventions to preserve organ utility are not justifiable, even with the help of the principle of double effect; claims that DCD conforms with the intent of the law and current accepted medical standards are misleading and inaccurate; and consensus statements by respected medical groups do not change these arguments due to their low quality including being plagued by conflict of interest. Moreover, some arguments in favor of DCD, while likely true, are "straw-man arguments," such as the great benefit of organ donation. The truth is that honesty and trustworthiness require that we face these problems instead of avoiding them. We believe that DCD is not ethically allowable because it abandons the dead donor rule, has unavoidable conflicts of interests, and implements premortem interventions which can hasten death. These important points have not been, but need to be fully disclosed to the public and incorporated into fully informed consent. These are tall orders, and require open public debate. Until this debate occurs, we call for a moratorium on the practice of DCD.

Donation after cardiocirculatory death in Canada

These recommendations are the result of a national, multidisciplinary, year-long process to discuss whether and how to proceed with organ donation after cardiocirculatory death (DCD) in Canada. A national forum was held in February 2005 to discuss and develop recommendations on the principles, procedures and practice related to DCD, including ethical and legal considerations. At the forum's conclusion, a strong majority of participants supported proceeding with DCD programs in Canada. The forum also recognized the need to formulate and emphasize core values to guide the development of programs and protocols based on the medical, ethical and legal framework established at this meeting. Although end-of-life care should routinely include the opportunity to donate organs and tissues, the duty of care toward dying patients and their families remains the dominant priority of health care teams. The complexity and profound implications of death are recognized and should be respected, along with differing personal, ethnocultural and religious perspectives on death and donation. Decisions around withdrawal of life-sustaining therapies, management of the dying process and the determination of death by cardiocirculatory criteria should be separate from and independent of donation and transplant processes. The recommendations in this report are intended to guide individual programs, regional health authorities and jurisdictions in the development of DCD protocols. Programs will develop based on local leadership and advance planning that includes education and engagement of stakeholders, mechanisms to assure safety and quality and public information. We recommend that programs begin with controlled DCD within the intensive care unit where (after a consensual decision to withdraw life-sustaining therapy) death is anticipated, but has not yet occurred, and unhurried consent discussions can be held. Uncontrolled donation (where death has occurred after unanticipated cardiac arrest) should only be considered after a controlled DCD program is well established. Although we recommend that programs commence with kidney donation, regional transplant expertise may guide the inclusion of other organs. The impact of DCD, including pre-and post-mortem interventions, on donor family experiences, organ availability, graft function and recipient survival should be carefully documented and studied.