Use Of Normothermic Regional Perfusion Research Articles

Neither Ethical nor Prudent: Why Not to Choose Normothermic Regional Perfusion.

In transplant medicine, the use of normothermic regional perfusion (NRP) in donation after circulatory determination of death raises ethical difficulties. NRP is objectionable because it restores the donor's circulation, thus invalidating a death declaration based on the permanent cessation of circulation. NRP's defenders respond with arguments that are tortuous and factually inaccurate and depend on introducing extraneous concepts into the law. However, results comparable to NRP's-more and higher-quality organs and more efficient allocation-can be achieved by removing organs from deceased donors and using normothermic machine perfusion (NMP) to support the organs outside the body, without jeopardizing confidence in transplantation's legal and ethical foundations. Given the controversy that NRP generates and the convoluted justifications made for it, we recommend a prudential approach we call "ethical parsimony," which holds that, in the choice between competing means of achieving a result, the ethically simpler one is to be preferred. This approach makes clear that policy-makers should favor NMP over NRP.

Kidney Transplantation Outcomes From Uncontrolled Donation After Circulatory Death: A Systematic Review and Meta-analysis.

Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD). MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD. Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts. Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

Outcomes of Heart Transplant Donation After Circulatory Death

BackgroundHeart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. ObjectivesWe sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. MethodsWe conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. ResultsDuring the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. ConclusionsIn the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Maintaining the permanence principle of death during normothermic regional perfusion in controlled donation after the circulatory determination of death: Results of a prospective clinical study

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.

Lung preservation: from perfusion to temperature.

This article will review the evidence behind elements of the lung preservation process that have remained relatively stable over the past decade as well as summarize recent developments in ex-vivo lung perfusion and new research challenging the standard temperature for static cold storage. Ex-vivo lung perfusion is becoming an increasingly well established means to facilitate greater travel distance and allow for continued reassessment of marginal donor lungs. Preliminary reports of the use of normothermic regional perfusion to allow utilization of lungs after DCD recovery exist, but further research is needed to determine its ability to improve upon the current method of DCD lung recovery. Also, research from the University of Toronto is re-assessing the optimal temperature for static cold storage; pilot studies suggest it is a feasible means to allow for storage of lungs overnight to allow for daytime transplantation, but ongoing research is awaited to determine if outcomes are superior to traditional static cold storage. It is crucial to understand the fundamental principles of organ preservation to ensure optimal lung function posttransplant. Recent advances in the past several years have the potential to challenge standards of the past decade and reshape how lung transplantation is performed.

The Future Is Now: OrganEx Technology and Its Implications for Transplant Medicine.

The Future Is Now: OrganEx Technology and Its Implications for Transplant Medicine.

Improved Organ Utilization and Better Transplant Outcomes With In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Death.

. We evaluated whether the use of normothermic regional perfusion (NRP) was associated with increased organ recovery and improved transplant outcomes from controlled donation after circulatory death (cDCD). . This is a retrospective analysis of UK adult cDCD donors' where at least 1 abdominal organ was accepted for transplantation between January 1, 2011, and December 31, 2019. . A mean of 3.3 organs was transplanted when NRP was used compared with 2.6 organs per donor when NRP was not used. When adjusting for organ-specific donor risk profiles, the use of NRP increased the odds of all abdominal organs being transplanted by 3-fold for liver ( P < 0.0001; 95% confidence interval [CI], 2.20-4.29), 1.5-fold for kidney ( P = 0.12; 95% CI, 0.87-2.58), and 1.6-fold for pancreas ( P = 0.0611; 95% CI, 0.98-2.64). Twelve-mo liver transplant survival was superior for recipients of a cDCD NRP graft with a 51% lower risk-adjusted hazard of transplant failure (HR = 0.494). In risk-adjusted analyses, NRP kidneys had a 35% lower chance of developing delayed graft function than non-NRP kidneys (odds ratio, 0.65; 95% CI, 0.465-0.901)' and the expected 12-mo estimated glomerular filtration rate was 6.3 mL/min/1.73 m 2 better if abdominal NRP was used ( P < 0.0001). . The use of NRP during DCD organ recovery leads to increased organ utilization and improved transplant outcomes compared with conventional organ recovery.

Protocol for a qualitative pilot study to explore ethical issues and stakeholder trust in the use of normothermic regional perfusion in organ donation in Canada

IntroductionThe process of controlled organ donation after circulatory determination of death (cDCDD) results in ischaemic injury to organs and leads to poorer outcomes in organ recipients. Although not yet used...

Normothermic regional perfusion in liver transplantation from donation after cardiocirculatory death: Technical, biochemical, and regulatory aspects and review of literature.

Organs from donation after circulatory death (DCD) are increasingly used for liver transplantation, due to the persisting organ shortage and waiting list mortality. However, the use of DCD grafts is still limited by the inferior graft survival rate and the increased risk of primary non-function and biliary complications when compared to brain death donors' grafts. Abdominal normothermic regional perfusion with extracorporeal membrane oxygenation (ECMO) is an in situ preservation strategy. which may mitigate ischemia-reperfusion injuries. and has been proposed to restore blood perfusion after the determination of death thus optimizing liver function before implantation. In this systematic review, we highlighted the clinical evidence supporting the use of normothermic regional perfusion in DCD liver underlying the pathophysiological mechanisms, and technical, logistic, and regulatory aspects. Despite the lack of properly designed, prospective, randomized trials, the current available data suggest beneficial effects of normothermic regional perfusion on clinical outcomes after liver transplantation.

Donación en asistolia controlada: cómo iniciar un programa

Introduction and objectivesDonation after circulatory death has become one of the main strategies to increase the number of donors. Until now, the heart of this type of donor was not evaluated due to the risk of ischaemic injury during the withdrawal of life support. In recent years, ex situ perfusion systems have initiated cardiac donation programmes after circulatory death that have demonstrated myocardial viability. The use of normothermic regional perfusion in our environment and the experience of other countries in cardiac recovery led us to develop a protocol for cardiac procurement in donation after circulatory death with in situ assessment and cold preservation. MethodsA multidisciplinary team was formed to create a cardiac extraction protocol with donation after circulatory death. After a phase of animal experimentation, the protocol was approved by the Ethics Committee for Health Care and by the National Transplant Organization. ResultsA protocol was drawn up establishing the criteria for donor and recipient selection and regulating the donation procedure with thoracic-abdominal perfusion after exclusion of the supra-aortic trunks. Cardiac evaluation is in situ and static preservation in cold storage. This protocol was sent to the rest of the donor hospitals and this led us to perform the first heart transplant in Spain with this donation modality. ConclusionsCardiac transplantation with donation after circulatory death is a clinical reality that will increase the number of potential donors. The technical characteristics of the procedure mean that this type of donation should be performed in experienced centres.

Outcome of Liver Transplants Using Donors After Cardiac Death With Normothermic Regional Perfusion

The incorporation of normothermic regional perfusion (NRP) to donors after cardiac death (DCD) allows the recovery of liver grafts without the deleterious effects on graft survival the super-rapid technique may cause. The aim of the present report is to determine if the use of NRP in Maastricht type III DCD donors achieves short- and medium-term results comparable to donors after brain death (DBD). This is an observational cohort study including 117 liver transplants executed between November 2016 and April 2021, divided into NRP (n=39) and DBD (n=78). Donors were younger in the NRP group (NRP 52 vs DBD 59.4 years; P < .005). Liver recipients in each study group were of similar age and severity of liver disease, although the predominant transplant indication in the NRP group was hepatocellular carcinoma. No differences in ischemia times were found. The incidence of early allograft disfunction and primary nonfunction was balanced between NRP and DBD. Eight patients required retransplant, all of them in the DBD group. No differences were found in biliary complications (NRP 12% vs DBD 5%; P=.104). Ischemic cholangiopathy affected a single DBD patient. Graft survival's Kaplan Meier curve shows a better outcome in the NRP group, although the difference did not reach significance (P=.075). The incorporation of perfusion machines, and specifically the NPR in situ, converts suboptimal liver grafts such as DCD into organs comparable to DBDs.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n =865) or RR (n =1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p=.261) and mortality at 1year (p=.111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p<.001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p=.034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation's Transplant Learning Journey.

Normothermic regional perfusion (NRP) in donation after circulatory death (DCD) is a safe alternative to insitu cooling and rapid procurement. An increasing number of countries and centres are performing NRP, a technically and logistically challenging procedure. This consensus document provides evidence-based recommendations on the use of NRP in uncontrolled and controlled DCDs. It also offers minimal ethical, logistical and technical requirements that form the foundation of a safe and effective NRP programme. The present article is based on evidence and opinions formulated by a panel of European experts of Workstream 04 of the Transplantation Learning Journey project, which is part of the European Society for Organ Transplantation.

Similar Results in Liver Transplantation From Controlled Donation After Circulatory Death Donors With Normothermic Regional Perfusion and Donation After Brain Death Donors: A Case-Matched Single-Center Study.

Although good results have been reported with the use of normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation (LT), there is a lack of evidence to demonstrate similar results to donation after brain death (DBD). We present a single-center retrospective case-matched (1:2) study including 100 NRP cDCD LTs and 200 DBD LTs and a median follow-up of 36months. Matching was done according to donor age, recipient Model for End-Stage Liver Disease score, and cold ischemia time. The following perioperative results were similar in both groups: alanine transaminase peaks of 909 U/L in the DBD group and 836 U/L in the cDCD group and early allograft disfunction percentages of 21% and 19.2%, respectively. The 1-year and 3-year overall graft survival for cDCD was 99% and 93%, respectively, versus 92% and 87%, respectively, for DBD (P = 0.04). Of note, no cases of primary nonfunction or ischemic-type biliary lesion were observed among the cDCD grafts. Our results confirm that NRP cDCD LT meets the same outcomes as those obtained with DBD LT and provides evidence to support the idea that cDCD donors per se should no longer be considered as "marginal donors" when recovered with NRP.

Kidney Transplants in Controlled Donation Following Circulatory Death, or Maastricht Type III Donors, With Abdominal Normothermic Regional Perfusion, Optimizing Functional Outcomes.

Warm ischemia time and ischemia-reperfusion damage result in higher rates of delayed graft function and primary nonfunction in kidney transplants (KTs) from controlled donation after circulatory death (cDCD). This study aimed to assess early and late kidney function and patient and graft survival of KT from cDCD preserved with normothermic regional perfusion (NRP) and to compare with KT from brain death donors (DBDs) and cDCD preserved with rapid recovery (RR). Patients who received a KT at our institution from 2012 to 2018 were included, with a minimum follow-up period of 1 y. They were categorized by donor type and conditioning methods: DBD, cDCD with NRP, and cDCD with RR. Early and late graft function, along with patient and graft survival were analyzed in all groups. A total of 182 KT recipients were included in the study (98 DBD and 84 cDCD). Out of the cDCDs, 24 kidneys were recovered with the use of NRP and 62 with RR; 22 of the 24 kidneys were ultimately transplanted. The cDCD using NRP group showed lower rates of delayed graft function compared with the cDCD with RR group (36.3% versus 46.7%, P = 0.01). Also, primary nonfunction rates were lower in the cDCD using NRP group (4.5% versus 6.4% cDCD-RR and 10.2% DBD). Patient survival rates were >90% in all groups. No differences were found in graft survival rates at 1 y. The use of abdominal NRP improves early function recovery of KT from cDCD, making their outcomes comparable with those of DBD.

Outcomes for circulatory death and brainstem death pancreas transplantation with or without use of normothermic regional perfusion.

Simultaneous pancreas and kidney transplantation is the optimum treatment for patients with type 1 diabetes and renal failure, providing survival benefit over deceased donor kidney transplant alone. Here the authors demonstrate that utilization of donation after circulatory death pancreases is a safe approach to expanding the donor pool with equivalent results to donation after brainstem death transplantation. They also demonstrate that pancreas transplantation after normothermic regional perfusion is feasible, but it will require ongoing prospective study to ensure that the benefits seen for liver transplantation do not come at the expense of pancreas transplant outcomes.

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice.

The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.

Liver Transplantation From Controlled Donors After Circulatory Death Using Normothermic Regional Perfusion: An Initial French Experience.

A national program of controlled donation after circulatory death (cDCD) began in France in 2014 involving the use of a standardized national protocol that involves the systematic use of normothermic regional perfusion (NRP). In this article, we describe in detail the French cDCD program. Between January 1, 2015, and December 31, 2018, 225 livers were offered for donation, resulting in 123 cDCD liver transplantations (LTs). The overall 90-day graft survival rate was 93.1% (95% confidence interval [CI], 85.9%-96.6%). A total of 21 of 123 LTs (17%) did not adhere strictly to the national protocol. The 1-year graft survival was significantly lower in the group deviating from the national protocol compared with those patients following the national protocol: 68.4% (95% CI, 42.8%-84.4%) versus 94.8% (95% CI, 86.5%-98.0%; P<0.01). There were 14 patients who died, including 2 after primary 2 after primary non function, and 10 related to liver cancer recurrence. Only 1 case of ischemic cholangiopathy was observed at month 18 in this series, and the patient underwent a successful retransplant. During the first 4 years, excellent LT results were observed where the national protocol was followed. Systematic use of NRP limits liver damage induced by warm ischemia and provides excellent cDCD organs for transplant.

Donation after circulatory death: possible strategies for in-situ organ preservation.

Donation after circulatory death (DCD) is an accepted strategy to expand the potential donor pool. The complexity of organ procurement from DCD donors requires the development of new strategies for organ preservation. Standard DCD organ recovery involves a super rapid technique, with cold thoracic and abdominal perfusion. However, the conventional methods of preservation based on static and hypothermic storage may not be the most appropriate for DCD grafts, especially in the presence of long warm ischemia times. New strategies designed to improve the preservation of in-situ DCD grafts include the use of normothermic regional perfusion (NRP) for abdominal organs and concomitant cold lung flushing. The use of in-situ NRP is a significant advance in abdominal organ retrieval and it has the potential to increase organ recovery rates due to its applicability in both controlled and uncontrolled DCD donors. We describe an innovative preservation strategy based on the combination of donor NRP for abdominal organ preservation and a normothermic open-lung approach with protective mechanical ventilation for lung preservation.

Kidney transplantation following uncontrolled donation after circulatory death.

The identification and utilization of kidneys from uncontrolled donation after circulatory death (uDCD) donors for transplantation may increase transplantation rates markedly. This article summarizes the latest international results from successful uDCD kidney transplant programmes and considers how such programmes may impact on the transplant waiting list. The results of more than 1000 uDCD donor kidney transplants have been reported since 2007 from France and Spain. Estimates from France, Spain and Sweden suggest that effective utilization of the potential uDCD donor pool might increase donation rates by 25%. The main concern relating to uDCD kidney transplantation is the high incidence of primary nonfunction with the incidence of primary nonfunction reported as 7-8% even with careful donor selection and the use of normothermic regional perfusion at the time of organ recovery. Notwithstanding, reported 1- year graft survival figures are equivalent to those from expanded criteria donors (ECD) and 10-year graft survival of between 72 and 82% was reported in the two single-centre series with longest reported follow-up period. Uncontrolled DCD kidney transplantation has been successfully implemented in several regions in France and Spain. Wider implementation of uDCD programmes would increase substantially the number of kidneys for transplantation, while maintaining acceptable transplant outcomes.