Donation After Circulatory Death Grafts Research Articles

Advances and Challenges of Thrombolytic Therapy for Donation After Circulatory Death Organs.

The demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long-term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post-transplantation complications, most organs considered high-risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior-quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.

Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction.

Background/Objectives: The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Methods: Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant. Results: Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. Metabolites like flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, increased during NRP and NMP and normalized post-transplant. Conclusions: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.

Risk scores for allograft failure: Are they still useful in liver recipients from donation after circulatory death?

Liver grafts from donation after circulatory death (DCD) are associated with a higher risk of early graft dysfunction, determined by the warm ischemia and cold ischemia times. It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies. To validate different graft and recipient survival scores in patients undergoing liver transplantation (LT) with DCD grafts. A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022. The United Kingdom (UK) risk score, early allograft dysfunction (EAD) Olthoff score, and model for early allograft function (MEAF) score were used to evaluate the risk of graft and recipient survival post-transplant. For survival analysis purposes, we used the Kaplan-Meier method, and the differences between subgroups were compared using the log-rank (Mantel-Cox) test. Sixty-five patients were included in the study. The UK risk score did not demonstrate predictive capacity for recipient or graft survival. However, in donors aged over 70 years old (18.4%), it significantly predicted graft survival (P < 0.05). According to Kaplan-Meier survival curves, graft survival rates at 6 months, 2 years, and 5 years in the futility group dramatically decreased to 50% compared to the other groups (log-rank 8.806, P < 0.05). The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival. Based on Kaplan-Meier survival curves, patients with a MEAF score ≥ 7 had a lower graft survival rate at 6 months, 2 years, and 5 years compared to patients with a lower MEAF score (log-rank 4.667, P < 0.05). In our series, both UK DCD risk score and MEAF score showed predictive capability for graft survival.

Hepatitis C-positive grafts for hepatitis C-negative recipients in liver transplantation: Buried treasure or depleting resource?

Long-term outcomes of using hepatitis C virus (HCV) positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival (GS). The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death (DCD) donors were seldom utilized in the study period. The 5-year GS rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD (p=0.56) or DCD (p=0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year GS to non-fibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or DCD grafts for HCV-negative recipients is comparable to that of other graft types, and that fibrotic grafts have the potential to expand the DBD donor pool.

Outcomes of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation Utilizing Extended Criteria Donor Grafts

The deceased donor shortage in the United States has led to increased utilization extended criteria donor (ECD) liver grafts. Centers often utilize ECD grafts in patients with low Model for End-Stage Liver Disease (MELD) scores, like patients with hepatocellular carcinoma (HCC). However, few studies have directly examined the outcomes of using ECD grafts in patients with HCC. Adults receiving liver transplantation (LT) for HCC between 2010 and 2020 were identified in the Organ Procurement and Transplantation Network database. Recipients were categorized according to donor type: standard criteria donor (SCD), extended criteria donor, donation after brain death (ECD-DBD), and donation after circulatory death (DCD). Multivariable Cox regression analysis identified variables associated with overall or graft survival at 3 years post-LT. Most patients received ECD-DBD grafts (51.4%); only 8.3% received DCD grafts. The time on the waitlist was similar for ECD and SCD recipients (P = .79). SCD recipients had higher 5-year overall survival post-LT than ECD-DBD or DCD recipients (79.1%, 77.1%, and 76.8%, respectively, P < .001). Similarly, 5-year graft survival was also highest in SCD recipients (SCD = 77.8%, ECD-DBD = 75.7%, and DCD = 72.2%, P < .001). In multivariable analysis, DCD grafts increased mortality risk (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.12-1.57, P = .001), but ECD-DBD grafts did not (HR = 1.10, 95% CI = 1.00-1.22, P = .052). DCD and ECD-DBD recipients had significantly lower overall and graft survival. However, the survival benefit of LT for patients with HCC greatly outweighs the small differences in patient and graft survival from using ECD grafts. Further research should investigate whether treatment of ECD grafts with machine perfusion may ameliorate this discrepancy.

The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study

Background. Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary. Methods. We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure. Results. Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT. Conclusions. This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

Dexmedetomidine and argon in combination against ferroptosis through tackling TXNIP-mediated oxidative stress in DCD porcine livers

Graft availability from donation after circulatory death (DCD) is significantly limited by ischaemia reperfusion (IR) injury. Effective strategies to mitigate IR injury in DCD grafts are essential to improve graft quality and expand the donor pool. In this study, liver grafts from DCD pigs were preserved in the University of Wisconsin (UW) solution saturated with 0.1 nM dexmedetomidine (Dex) and various concentrations of noble gases Argon (Ar) and/or Xenon (Xe) at 4 °C for 24 or 72 h. The combined 50% Ar and Dex provided maximum protection to liver grafts by reducing morphological damage, apoptosis, necroptosis, ferroptosis, hepatocyte glycogen depletion, reticulin framework collapse, iron deposition, and oxidative stress. In vitro, human liver Hep G2 cells were preserved in the UW solution saturated with 0.1 nM Dex and 50% Ar in combination at 4 °C for 24 h, followed by recovery in medium at 37 °C for up to 48 h to mimic clinical IR injury. This treatment significantly increased the expression of anti-oxidative stress proteins by promoting the translocation of thioredoxin-interacting protein (TXNIP) to mitochondria, thereby inhibiting ferroptosis, increasing plasma membrane integrity, and maintaining cell viability.In summary, The combination of 0.1 nM Dex and 50% Ar may be a promising strategy to reduce ferroptosis and other form cell death, and preserve liver grafts.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation. SNMP at 22-25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys. In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs. These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.

Financial impact of donation after circulatory death heart transplantation: A single-center analysis.

Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain-dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex-situ machine perfusion to in-situ organ perfusion employed during DCD recovery. We performed 58 DBD and 22 DCD heart-alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA-NRP) and six with direct procurement followed by normothermic machine perfusion (DP-NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P=.72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P=.49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA-NRP was $155,955 in comparison to $223,399 for DP-NMP (P=.21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA-NRP ($242, 657vs. $175,768; P=.34). Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation.

Outcomes of liver transplantation for hepatocellular carcinoma in donation after circulatory death compared with donation after brain death: A systematic review and meta-analysis

Due to organ shortages, liver transplantation (LT) using donation-after-circulatory-death (DCD) grafts has become more common. There is limited and conflicting evidence on LT outcomes using DCD grafts compared to those using donation-after-brain death (DBD) grafts for patients with hepatocellular carcinoma (HCC). We aimed to summarize the current evidence on the outcomes of DCD-LT and DBD-LT in patients with HCC. Online databases were searched for studies comparing DCD-LT and DBD-LT outcomes in patients with HCC and a meta-analysis was conducted using fixed- or random-effects models. Five studies involving 487 (33.4%) HCC DCD-LT patients and 973 (66.6%) DBD-LT patients were included. The meta-analysis showed comparable 1-year [relative risk (RR)=0.99, 95%CI:0.95 to 1.03, p=0.53] and 3-year [RR=0.99, 95%CI:0.89 to 1.09, p=0.79] recurrence-free survival. The corresponding 1-year [RR=0.98, 95%CI:0.93 to 1.03, p=0.35] and 3-year [RR=0.94, 95%CI:0.87 to 1.01, p=0.08] patient survival and 1-year [RR=0.91, 95%CI:0.71 to 1.16, p=0.43] and 3-year [RR=0.92, 95%CI:0.67 to 1.26, p=0.59] graft survival were also comparable. There were no significant differences between the two cohorts regarding the tumor characteristics, donor/recipient risk factors and the incidence of post-operative complications, including acute rejection, primary non-function, biliary complications and retransplantation. Based on the current evidence, it has been found that comparable outcomes can be achieved in HCC patients using DCD-LT compared to DBD-LT, particularly when employing good quality graft, strict donor and recipient selection, and effective surgical management. The decision to utilize DCD-LT for HCC patients should be personalized, taking into consideration the risk of post-LT HCC recurrence. (PROSPERO ID: CRD42023445812).

Modern-Day Practice of DCD Liver Transplantation: Controversies, Innovations, and Future Directions.

Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement. New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts. As these modalities enter routine clinical practice, DCD utilization will continue to increase, and liver allocation policies in turn will evolve to reflect this growing practice. This review describes recent progress in DCD LT, current challenges with utilization of DCD liver allografts, and how novel technologies and policies could impact the future of the field.

Utilization of Paragonix Sherpapak Cardiac Transport System for the Preservation of Donor Hearts After Circulatory Death

Donation after circulatory death (DCD) heart transplantation is being increasingly adopted by transplant centers. The optimal method of DCD heart preservation during transport after in situ thoracoabdominal normothermic regional perfusion (TA-NRP) is not known. We evaluated our experience with the Paragonix SherpaPak Cardiac Transport System (SCTS) for the transport of DCD cardiac allografts after TA-NRP recovery between January 2021 and December 2022. We collected and evaluated donor characteristics, allograft ischemic intervals, and recipient baseline demographic and clinical variables, and short-term outcomes. Twelve recipients received DCD grafts recovered with TA-NRP and transported in SCTS during the study period. The median age of 10 male and 2 female donors was 32 years (min 15, max 38). The median duration of functional warm ischemia was 12 minutes (min 8, max 22). Hearts were preserved in SCTS for a median of 158 minutes (min 37, max 224). Median recipient age was 61 years (min 28, max 70). Ten recipients (83%) survived to hospital discharge, with one death attributable to graft dysfunction (8%). The median vasoactive-inotropic (VIS) score at 72 hours post-transplantation of the entire cohort was 6 (min 0, max 15). The median length of intensive care unit stay in hospital survivors was 5 days (min 3, max 17) days and hospital stay 17 days (min 9, max 37). The Paragonix SCTS provides efficacious preservation of DCD grafts for ≥3.5 hours. Organs transported with this device showed satisfactory post-transplantation function.

Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP. Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed. Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger ( P < 0.001) and had lower Kidney Donor Profile Index ( P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger ( P < 0.001) and more likely to be blood group O ( P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival ( P = 0.8) and all-cause graft failure ( P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis. Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.

DCD liver transplant in patients with a MELD over 35.

Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

Metabolic Outcomes After Pancreas Transplant Alone From Donation After Circulatory Death Donors-The UK Transplant Registry Analysis.

Extrapolating data from early DCD (donation after circulatory death) kidney transplantation, pancreas transplants from DCD grafts were feared to have worse metabolic outcomes. Hence, we aimed to address the question of pancreas transplant alone (PTA) from DCD donors-are our concerns justified? A UK transplant registry analysis of 185 PTA performed between 2005 and 2018 was done. All early graft losses (<3months) were excluded to allow focus on the metabolic outcomes (HbA1c, weight gain and incidence of secondary diabetic macrovascular complications). The aim was to compare the metabolic outcomes, rejection rates (including the need for steroids), patient and graft survival between DBD (Donation after brainstem death) and DCD groups. After excluding early graft losses, data from 162 PTA (DBD = 114 and DCD = 48) were analyzed. Body mass index of the donor was less in DCD group (DBD = 23.40 vs. DCD = 22.25, p = 0.006) and the rest of the baseline transplant characteristics were comparable. There were no significant differences in the HbA1c, weight gain, rejection rate, and incidence of secondary diabetic macrovascular complications post-transplant between DBD and DCD recipients. The 1-, 5-, and 10-year patient and graft survival were similar in both the groups. PTA from DCD donors have equivalent metabolic outcomes and survival (patient/graft) as that of DBD donors.

Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts

Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70y of age. 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71y (P < 0.01). Recipients had similar Intensive care unit (P=0.82) and hospital (P=0.14) lengths of stay, and there were no differences in patient (P=0.68) or graft (P=0.38) survival. When comparing donation after brain death and DCD grafts in those >70y, there were no differences in patient (P=0.89) or graft (P=0.71) survival. Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.

Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment.

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14years. Candidates for multi-organ or re-LT, donors aged ≥65years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.

Addressing inadequate blood flow during normothermic regional perfusion for in-situ donation after circulatory death grafts preservation.

Donation after circulatory death (DCD) has emerged as attainable strategy to tackle the issue of organ shortage, expanding the donor pool. The DCD concept has been applied to the multiple declinations of circulatory arrest, as per the Modified Maastricht Classification. Notwithstanding, whichever the scenario, DCD donors experience a variable warm ischemia time whose correlation with graft dysfunction is ascertained. This applies to both "controlled" (cDCD) donors (i.e., the timespan from the withdrawal of life-sustaining therapies to the onset of in-situ perfusion), and "uncontrolled" DCD (uDCD) (i.e., the low-flow period during cardiopulmonary resuscitation - CPR). This sums up to the no-flow time from cardiac arrest to the start of CPR for uDCD donors, and to the no-touch period for both uDCDs and cDCDs. Static and hypothermic storage may not be appropriate for DCD grafts. In order to overcome this ischemic insult, extracorporeal membrane oxygenation devices are adopted to guarantee the in-situ grafts preservation by means of techniques such as the normothermic regional perfusion (NRP) which consists in a selective abdominal perfusion obtained via the endovascular or surgical occlusion of the thoracic aorta. The maintenance of an adequate pump flood throughout NRP is therefore a sine qua non to accomplish the DCD donation. The issue of insufficient pump flow during NRP is prevalent and clinically significant but its management remains technically challenging and not standardized. Hereby we propose a systematic algorithmic approach to address this relevant occurrence.

Donation after Circulatory Death Grafts Have Comparable Outcomes to Donation after Brain Death Grafts in Liver Transplantation

Introduction: In the United States, 30% of donation after circulatory death (DCD) grafts are discarded for liver transplantation (LT). DCD grafts can mitigate liver organ shortage but is underused due to the believe of poor outcomes in graft and patient survival. Recent studies have shown comparable outcomes to donation after brain death (DBD). The aim of this study is to review our experience with the use of DCD grafts. Methods: Retrospective single center study, whole grafts transplanted between January 2014 and December 2021 were included. Propensity score match was done using recipient age, recipient gender, MELD score, wait time, number of previous LT, cold ischemia time, year of LT and surgeon as cofounders. Multivariate Cox-regression models were created with significant variables in the univariate analysis. Finally, Kaplan-Meier curves with log-rank test were performed. Results: A total of 63 DCD and 148 DBD grafts were included. The patients were predominantly males (59.2%), median age was 58 (IQR 49-65), the most common reason for transplantation was alcoholic cirrhosis (20.4%) and were listed for their first LT (95.7%). Number of transplants (HR:15.39, 95%CI: 3.56-66.49, p < 0.001) and BMI (HR:1.1, 95%CI: 1.01-1.2, p = 0.03) were associated to graft loss. DCD was not associated with graft (HR:0.47, 95%CI: 0.14-1.58, p = 0.2) or patient (HR:0.33, 95%CI: 0.08-1.42, p = 0.1) survival. Graft (92.9% DBD vs 96.8% DCD, p = 0.2) and patient (93.6% DBD vs 100% DCD, p = 0.1) 2-year survival were similar. Conclusion: When matching different cofounders, the use of DCD grafts has comparable outcomes to those DBD grafts.

Comparison of Outcomes in High Donation after Circulatory Death Liver Transplantation Usage Centers in the Acuity Circles Era

INTRODUCTION: The recent acuity circles (AC) liver allocation policy has increased rates of donation after circulatory death (DCD) liver transplantation. We hypothesize that transplant centers with high-volume DCD graft usage may have differing outcomes. METHODS: All adult DCD transplant recipients in the United Network for Organ Sharing (UNOS) STAR file from January 11, 2016, to September 30, 2021, were included. Living liver grafts, pediatric, and nonkidney simultaneous transplantation were excluded. The top decile of DCD transplant centers by volume per year were identified. Six-month and 1-year patient and liver graft survival were compared with bottom 90% usage centers by using propensity score–matched fine gray regression models. Outcomes were stratified by pre-AC (January 11, 2016 to February 3, 2020) and post-AC (February 4, 2020 to September 30, 2020) eras (Figure). Transplant recipients that cross eras were censored on the last day of the pre-AC era. RESULTS: Included in this study were 2,299 DCD liver transplantation recipients : 2012 in pre-AC and 287 in post-AC eras. High DCD volume (top decile) centers had significantly improved 6-month (hazard ratio 0.32, 95% CI 0.11 to 0.91, p = 0.033) and 1-year (hazard ratio 0.42, 95% CI 0.17 to 0.98, p = 0.043) patient survival in the post-AC era compared with bottom 90% centers by volume. No significant differences were noted in 6-month or 1-year liver graft survival in either era. CONCLUSION: The top decile DCD transplantation volume centers have improved 6-month and 1-year patient survival compared with the lower volume centers with the introduction of the AC policy.Figure