Addressing organ shortages: progress in donation after circulatory death for liver transplantation
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ABSTRACT:
SUBMITTER: Nostedt JJ
PROVIDER: S-EPMC7828961 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Addressing organ shortages: progress in donation after circulatory death for liver transplantation
Nostedt Jordan J. JJ Shapiro James J Freed Darren H. DH Bigam David L. DL
Canadian journal of surgery. Journal canadien de chirurgie 20200320 2
Reducing wait list mortality among patients awaiting liver transplantation remains a substantial challenge because of organ shortage. In efforts to expand the donor pool there has been a trend toward increased use of donation after circulatory death (DCD) liver grafts. However, these marginal grafts are prone to higher complication rates, particularly biliary complications. In addition, many procured DCD livers are then deemed unsuitable for transplant. Despite these limitations, DCD grafts repr ...[more]
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Project description:BackgroundDonation after circulatory death (DCD) liver transplantation (LT) has become an effective mechanism for expanding the donor pool and decreasing waitlist mortality. However, it is unclear if low-volume DCD centers can achieve comparable outcomes to high-volume centers.MethodsFrom 2011 to 2019 utilizing the United Network for Organ Sharing (UNOS) database, liver transplant centers were categorized into tertiles based on their annual volume of DCD LTs. Donor selection, recipient selection, and survival outcomes were compared between very-low volume (VLV, n = 1-2 DCD LTs per year), low-volume (LV, n = 3-5), and high-volume (HV, n > 5) centers.ResultsOne hundred and ten centers performed 3273 DCD LTs. VLV-centers performed 339 (10.4%), LV-centers performed 627 (19.2%), and HV-centers performed 2307 (70.4%) LTs. 30-day, 90-day, and 1-year patient and graft survival were significantly increased at HV-centers (all P < .05). Recipients at HV-centers had shorter waitlist durations (P < .01) and shorter hospital lengths of stay (P < .01). On multivariable regression, undergoing DCD LT at a VLV-center or LV-center was associated with increased 1-year patient mortality (VLV-OR:1.73, 1.12-2.69) (LV-OR: 1.42, 1.01-2.00) and 1-year graft failure (VLV-OR: 1.79, 1.24-2.58) (LV-OR: 1.28, .95-1.72).DiscussionIncreased annual DCD liver transplant volume is associated with improved patient and graft survival.
| S-EPMC9287056 | biostudies-literature
Project description:Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally. Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems. Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not. Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.
| S-EPMC8766343 | 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:BackgroundDuring orthotopic liver transplantation, allograft reperfusion is a dynamic point in the operation and often requires vasoactive medications and blood transfusions. Normothermic machine perfusion (NMP) of liver allografts has emerged to increase the number of transplantable organs and may have utility during donation after circulatory death (DCD) liver transplantation in reducing transfusion burden and vasoactive medication requirements.MethodsThis is a single-center retrospective study involving 226 DCD liver transplant recipients who received an allograft transported with NMP (DCD-NMP group) or with static cold storage (DCD-SCS group). Veno-venous bypass was not used in any patients. Infusion doses of norepinephrine, epinephrine, and vasopressin as well as bolus doses of vasoactive medications during reperfusion were recorded. Blood component therapy was recorded according to phase of liver transplantation and during the first 24 hours postprocedure.ResultsA total of 103 recipients in the DCD-NMP group and 123 patients in the DCD-SCS group were included. Post-reperfusion syndrome (PRS) incidence was reduced in the DCD-NMP group compared to the DCD-SCS group (10.7% [95% confidence interval, CI, 5.5%-18.3%] vs 42.3% [95% CI, 33.4%-51.5%]; P < .001). During the reperfusion period, patients in the DCD-SCS group required increased bolus doses of epinephrine and vasopressin compared to the DCD-NMP group (24.6 vs 7.5 µg; P < .001) and (5.4 vs 2.4 units; P < .001), respectively. The DCD-SCS group received a higher infusion dose of epinephrine during anhepatic phase, at reperfusion, and up to 90 minutes after reperfusion. In the postreperfusion period, there were significant increases in the transfusion of red blood cells (RBCs; 5.3 vs 3.7 units; P = .006), fresh frozen plasma (FFP; 3.4 vs 1.9 units; P < .001), cryoprecipitate (2.7 vs 1.8 pooled units; P = .015) and platelets (0.9 vs 0.4 units; P = .008) in the DCD-SCS group compared to the DCD-NMP group. During the first 24 hours postprocedure, transfusion of RBCs, FFP, and cryoprecipitate in the DCD-SCS group was increased compared to the DCD-NMP group ([2.6 vs 1.7 units; P = .028], [1.6 vs 0.8 units; P < .001], [1.5 vs 0.9 pooled units; P = .031]) respectively. Administration of tranexamic acid was more frequent in the DCD-SCS group during the post-reperfusion period compared to the DCD-NMP group (13% [95% CI, 5.7%-17.4%] vs 3.9% [95% CI, 1.1%-9.6% 95%]; P = .018).ConclusionsIn DCD liver transplantation, use of NMP was associated with reduced incidence of PRS and decreased vasopressor and inotrope requirements at the time of allograft reperfusion compared to using SCS. Additionally, NMP was associated with reduced transfusion of all blood product components as well as antifibrinolytic agent administration in the post-reperfusion period. Reduced transfusion burden in the DCD-NMP group also occurred during the first 24 hours posttransplant.
| S-EPMC11805485 | biostudies-literature
Project description:Lung transplantation through controlled donation after circulatory death (cDCD) has slowly gained universal acceptance with reports of equivalent outcomes to those through donation after brain death. In contrast, uncontrolled DCD (uDCD) lung use is controversial and requires ethical, legal and medical complexities to be addressed in a limited time. Consequently, uDCD lung use has not previously been reported in the United States. Despite these potential barriers, we present a case of a patient with multiple gunshot wounds to the head and the body who was unsuccessfully resuscitated and ultimately became an uDCD donor. A cytomegalovirus positive recipient who had previously consented for CDC high-risk, DCD and participation in the NOVEL trial was transplanted from this uDCD donor, following 3 h of ex vivo lung perfusion. The postoperative course was uneventful, and the recipient was discharged home on day 9. While this case represents a "best-case scenario," it illustrates a method for potential expansion of the lung allograft pool through uDCD after unsuccessful resuscitation in hospitalized patients.
| S-EPMC4273571 | biostudies-literature
Project description:BackgroundIn The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included.MethodsBetween 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF.ResultsIn our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF.ConclusionsConsidering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.
| S-EPMC10566979 | biostudies-literature
Project description:Compared to donation after brain death (DBD), livers procured for transplantation from donation after circulatory death (DCD) donors experience more ischemia-reperfusion injury and higher rates of ischemic cholangiopathy due to the period of warm ischemic time (WIT) following withdrawal of life support. As a result, utilization of DCD livers for liver transplant (LT) has generally been limited to short WITs and younger aged donor grafts, causing many recovered DCD organs to be discarded without consideration for transplant. This study assesses how DCD liver utilization and outcomes have changed over time, using OPTN data from adult, first-time, deceased donor, whole-organ LTs between January 1995 and December 2019. Results show that increased clinical experience with DCD LT has translated into increased use of livers from DCD donors, shorter ischemic times, shorter lengths of hospitalization after transplant, and lower rates of retransplantation. The data also reveal that over the past decade, the rate of increase in DCD LTs conducted in the United States has outpaced that of DBD. Together, these trends signal an opportunity for the field of liver transplantation to mitigate the organ shortage by capitalizing on DCD liver allografts that are currently not being utilized.
| S-EPMC7969458 | biostudies-literature
Project description:Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.
| S-EPMC11377255 | biostudies-literature
Project description:BackgroundDonation after circulatory death (DCD) with cardiopulmonary bypass for thoracoabdominal normothermic regional perfusion (TA-NRP) has led to increased use of donor hearts. Rejection rates and long-term survival outcomes are not known.MethodsA single-center retrospective cohort review of patients who underwent DCD heart transplantation from January 2020 to December 2023 was performed. Donor and recipient characteristics, operative characteristics, and posttransplantation outcomes were analyzed. Subgroup analysis comparing co-localized vs distant donors and recipients was performed. The primary end point was 1-year survival. Secondary end points included incidences of primary graft dysfunction (PGD), cardiac allograft vasculopathy (CAV), rejection rate, and overall mortality. Our TA-NRP protocol has remained the same, consisting of sternotomy, ligation of aortic arch vessels, establishment of cardiopulmonary bypass, reintubation, resuscitation of the heart, and cold static storage during transport.ResultsIn total, 32 recipients underwent DCD heart transplantation, including 26 isolated hearts, 3 heart-lungs, and 3 heart-kidneys. The median age was 56 years for recipients and 39 years for donors; 21 donors and recipients were co-localized, whereas 11 were distant. One-year survival was 100%. Two patients required mechanical circulatory support for PGD. Four patients experienced grade 2R acute cellular rejection. Five patients had grade 1 CAV at 1 year. On subgroup analysis, distant donors and recipients had longer warm (47 vs 30 minutes; P < .005) and cold (213 vs 76 minutes; P < .005) ischemia times, without any other differences.ConclusionsOutcomes after DCD heart transplantation using TA-NRP remain encouraging with acceptable rates of rejection, PGD, CAV, and survival at 1 year.
| S-EPMC11910781 | biostudies-literature
Project description:BackgroundHeart failure remains a significant cause of morbidity and mortality internationally. With significant disparities in supply and demand for donor organs and recipients, there has been a growing need to expand the donor pool. Donation after circulatory death (DCD) heart transplantation offers such a method, with ex-situ machine perfusion (ESMP) and thoracoabdominal normothermic reperfusion (NRP) offering two potential methods of procuring DCD organs. This systematic review and meta-analysis aims to evaluate the current literature and compare DCD with donation after brain death (DBD) as well as DCD methods of transplantation.MethodsA systematic literature review was performed according to PRISMA guidelines. Primary outcomes were 30-day, 6- and 12-month survival, as well as primary graft dysfunction (PGD) and acute rejection. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) LOS and temporary dialysis. Weighted averages were utilised to summarise data with funnel plots utilised for comparisons. Reconstructed Kaplan-Meier curves were utilised to evaluate mid-term survival.ResultsA total of 10 studies were included evaluating 923 DCD recipients and 7,236 DBD recipients. Survival for DCD and DBD patients at 6 months was 93% and 91% respectively [odds ratio (OR), 1.5; 95% confidence interval (CI): 1.0-2.2; P<0.05] and at 12 months 93% and 91% for DCD and DBD respectively (OR 0.77, 95% CI: 0.1-5.3, P=0.8). Acute rejection was 15% and 19% in DCD and DBD patients respectively (OR, 1.0; 95% CI: 0.6-1.8; P=0.9). Thirty-day survival was similar between NRP (96.9%) and direct procurement and perfusion (DPP) (97%) (OR, 0.8; 95% CI: 0.2-3.9; P=0.8). PGD was higher in DCD (17%) compared with DBD (8%) patients (OR, 1.9; 95% CI: 0.98-3.7; P=0.06) whilst PGD for DPP and NRP was 21% and 14% respectively.ConclusionsDCD may offer comparable outcomes to DBD in short and mid-term outcomes, although PGD remains a concern. Further comparative research is required to delineate the role of both techniques in the current transplant landscape.
| S-EPMC11811570 | biostudies-literature