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.

Getting out of the box: the future of the UK donation after circulatory determination of death heart programme.

Heart failure imposes a significant burden on all health care systems and has a 5-year mortality of 50%. Heart transplantation and ventricular assist device (VAD) implantation are the definitive therapies for end stage heart disease, although transplantation appears to offer superior long-term survival and quality of life over VAD implantation. Transplantation is limited by a shortage in donor hearts, resulting in considerable waiting list mortality. Donation after circulatory determination of death (DCD) offers a significant uplift in the number of donors for heart transplantation. The outcomes both from the UK and internationally have been exciting, with outcomes at least as good as conventional donation after brain death (DBD) transplantation. Currently, DCD hearts are reperfused using ex-situ machine perfusion (ESMP). Whilst ESMP has enabled the development of DCD transplantation, it comes at significant cost, with the per run cost of approximately GBP £90,000. In-situ perfusion of the heart, otherwise known as thoraco-abdominal normothermic regional perfusion (taNRP) is cheaper, but there are ethical concerns regarding the potential to restore cerebral perfusion in the donor. We must determine whether there is any cerebral circulation during in-situ perfusion of the heart to ensure that it does not invalidate the diagnosis of death and potentially violate the dead donor rule. Besides this, there is a need for a randomised controlled trial to definitively determine whether taNRP offers any clinical advantages over ex-situ machine perfusion. This viewpoint article explores these issues in more detail.

The international experience of in-situ recovery of the DCD heart: a multicentre retrospective observational study.

Background: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. Method: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. Findings: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). Interpretation: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. Funding: None of the authors have a financial relationship with a commercial entity that has an interest in the subject.

Introducing Machine Perfusion into Routine Clinical Practice for Liver Transplantation in the United States: The Moment Has Finally Come.

While adoption of machine perfusion technologies into clinical practice in the United States has been much slower than in Europe, recent changes in the transplant landscape as well as device availability following FDA approval have paved the way for rapid growth. Machine perfusion may provide one mechanism to maximize the utilization of potential donor liver grafts. Indeed, multiple studies have shown increased organ utilization with the implementation of technologies such as ex-situ normothermic machine perfusion (NMP), ex-situ hypothermic machine perfusion (HMP) and in-situ normothermic regional perfusion (NRP). The current review describes the history and development of machine perfusion utilization in the Unites States along with future directions. It also describes the differences in landscape between Europe and the United States and how this has shaped clinical application of these technologies.

Early patient and liver allograft outcomes from donation after circulatory death donors using thoracoabdominal normothermic regional: a multi-center observational experience.

Background: Donation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization and patient and allograft outcomes. Given the increasing US experience with TA-NRP DCD recovery, we evaluated outcomes of DCD liver allografts transplanted after TA-NRP. Methods: Liver allografts transplanted from DCD donors after TA-NRP were identified from 5/1/2021 to 1/31/2022 across 8 centers. Donor data included demographics, functional warm ischemic time (fWIT), total warm ischemia time (tWIT) and total time on TA-NRP. Recipient data included demographics, model of end stage liver disease (MELD) score, etiology of liver disease, PNF, cold ischemic time (CIT), liver function tests, intensive care unit (ICU) and hospital length of stay (LOS), post-operative transplant related complications. Results: The donors' median age was 32 years old and median BMI was 27.4. Median fWIT was 20.5 min; fWIT exceeded 30 min in two donors. Median time to initiation of TA-NRP was 4 min and median time on bypass was 66 min. The median recipient listed MELD and MELD at transplant were 22 and 21, respectively. Median allograft CIT was 292 min. The median length of follow up was 257 days. Median ICU and hospital LOS were 2 and 7 days, respectively. Three recipients required management of anastomotic biliary strictures. No patients demonstrated IC, PNF or required re-transplantation. Conclusion: Liver allografts from TA-NRP DCD donors demonstrated good early allograft and recipient outcomes.

The role of transesophageal echocardiography in guiding heart donation after circulatory death.

Heart donation after circulatory death (DCD) can significantly expand the heart donor pool, helping to overcome the problem of organ shortage and the increase in waiting list mortality and morbidity. To improve the outcome of DCD heart transplantation, thoraco-abdominal normothermic regional perfusion (TA-NRP) can be performed by selectively restoring circulation followed by in vivo functional heart assessment. Here, we report on the use of periprocedural transoesophageal echocardiography (TOE) as a minimally invasive cardiac assessment tool during different stages of a DCD heart procurement procedure using TA-NRP. We conclude that TOE is a valuable method to assess the donor heart for transplantation eligibility before and after withdrawal of life-sustaining therapy and during subsequent TA-NRP.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.