Thoraco-abdominal Normothermic Regional Perfusion Research Articles

Dilemmas concerning heart procurement in controlled donation after circulatory death.

With an expanding population at risk for heart failure and the resulting increase in patients admitted to the waiting list for heart transplantation, the demand of viable organs exceeds the supply of suitable donor hearts. Use of hearts after circulatory death has reduced this deficit. Two primary techniques for heart procurement in circulatory death donors have been described: direct procurement and perfusion and thoraco-abdominal normothermic regional perfusion. While the former has been accepted as an option for heart procurement in circulatory death donors, the latter technique has raised some ethical questions in relation to the dead donor rule. In this paper we discuss the current dilemmas regarding these heart procurement protocols in circulatory death donors.

Thoracoabdominal normothermic regional perfusion in donation after circulatory death does not restore brain blood flow

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

The impact of thoracoabdominal normothermic regional perfusion on early outcomes in donation after circulatory death lung transplantation

Thoracoabdominal normothermic regional perfusion has emerged as an alternative method to procure donation after circulatory death (DCD) hearts, but its impact on concomitantly procured lung allografts remains unclear. The United Network for Organ Sharing database identified 627 DCD donors whose hearts were procured (211 in situ perfused, 416 directly procured) between December 2019 to December 2022. Lung utilization rates were 14.9% (63/422) for in situ perfused donors and 13.8% (115/832) for directly procured donors (p=0.80). Following transplantation, lung recipients from in situ perfused donors required numerically lower rates of extracorporeal membrane oxygenation (7.7% vs 17.0%, p=0.26) and mechanical ventilation (34.6% vs 47.2%, p=0.29) at 72 hours. Six-month post-transplant survival was similar between groups (85.7% vs 89.1%, p=0.67). These results suggest that the use of thoracoabdominal normothermic regional perfusion in DCD heart procurement may not adversely impact recipients of concomitantly procured lung allografts.

Expanding Heart Donor Pool With a Broken Heart: Cardiac Transplant From Donor Following Circulatory Death With Takotsubo Syndrome.

Owing to the growth of patients with advanced heart failure and limited potential for donation after brain death, expanding donor source with hearts from controlled donation after circulatory death (cDCD) and meeting extended criteria are essential strategies. We present the first case of a patient who successfully underwent cardiac transplant (CT) from cDCD with Takotsubo syndrome (TTS). The donor was a 49-y-old man without risk factors for coronary artery disease (CAD) and terminal amyotrophic lateral sclerosis with respiratory failure and mechanical ventilation support. A decision was made with patient’s family to withdraw life-sustaining therapies (WLSTs). Organ donation option was presented and consented, and cDCD Maastricht Classification III1 was considered suitable. He presented normal blood tests, electrocardiogram, and echocardiogram. The cDCD process was performed using an extracorporeal membrane oxygenation circuit to perform thoracoabdominal normothermic regional perfusion.2 During intraoperative evaluation, transesophageal echocardiography revealed normal left ventricular ejection fraction (LVEF). However, after WLST, moderate dysfunction (LVEF 37%) and apical ballooning suggestive of TTS were observed (Figure 1A), continuing present after thoracoabdominal normothermic regional perfusion withdrawal and organ extraction. Epicardial coronary arteries palpation did not reveal pathology.FIGURE 1.: A, Intraoperative transesophageal echocardiography evaluation that shows the left ventricle in diastole and systole with apical akinesia and preserved contractility of basal segments. B, The 12-lead electrocardiogram reveals T wave inversion and prolonged QT interval. C, A graph of heart recovery timeline based on the high-sensitivity troponin T levels, left ventricular ejection fraction, and inotrope support, correlated with the d after cardiac transplant. D, Normal right and left coronary arteries in the post cardiac transplant protocol–based coronary angiography. LVEF, left ventricular ejection fraction.The heart recipient was a 52-y-old man with severe, irreversible ischemic cardiomyopathy and 10 d with a ventricular assist device, listed for CT after excluding severe comorbidities and a multidisciplinary team discussion. An orthotopic transplant was performed using the bicaval technique, with spontaneous heartbeat and cold ischemia time of 86 min. He required minimal vasoactive support, withdrawn 48 h after CT. The electrocardiogram showed diffuse negative T waves and prolonged QTc interval (Figure 1B), and peak level of high-sensitivity troponin T was 2115 ng/L. Six days after CT, LVEF normalized. The timeline of heart recovery is represented in Figure 1C. The coronary angiography ruled out donor CAD (Figure 1D). The patient was discharged 30 d after CT and is doing well 43 wk after. Serial echocardiograms reveal normal wall motion and function. DISCUSSION Although TTS and CT have been indirectly associated, few cases have been published on donor hearts with TTS, these with no compromised survival3; none in cDCD. Similar pathophysiological aspects, present in TTS and cDCD, could be responsible for the phenomenon that occurred during CT. In the cDCD, the heart experiences a warm ischemia period during the WLST, cardiac arrest, and CT. This implies ischemia–reperfusion injury: activation of inflammatory and coagulation cascades and release of catecholamines.4 The mechanisms behind TTS, clinical condition characterized by acute transient left ventricular dysfunction, remain unknown. The most widely accepted theory is catecholamine-induced cardiotoxicity, and growing evidence is arising for myocardial inflammation, endothelial and microcirculation dysfunction, and neurohormonal alterations.5 Because of donor’s age, low-risk profile of CAD, and echocardiographic abnormalities, TTS was suspected. The post-CT protocol–based coronary angiography ruled out obstructive CAD or atherosclerotic plaque rupture. There was a rapid normalization of LVEF, negative T waves in the electrocardiogram, and elevated cardiac enzymes. This fulfilled the most widely used TTS diagnostic criteria.5 A pre-CT coronary angiography in patients >40 y or at risk of CAD could avoid ruling out hearts with left ventricular dysfunction. CONCLUSION The pathophysiological knowledge of cDCD and TTS could increase CT rates. This first experience in cDCD should be cautiously interpreted and analyzed individually in future cases.

Six-month abdominal transplant recipient outcomes from donation after circulatory death heart donors: A retrospective analysis by procurement technique

Standard US practice for donation after circulatory death (DCD) abdominal organ procurement is superrapid recovery (SRR). A newer approach using thoracoabdominal normothermic regional perfusion (TA-NRP) shows promise for better recipient outcomes for all organs, but there are few reports of abdominal recipient outcomes from TA-NRP donors. We used the United Network for Organ Sharing data to identify all cardiac DCD donors from October 1, 2020, to May 20, 2022, and categorized them by recovery procedure (SRR vs TA-NRP). We then identified all liver, kidney, and pancreas recipients of these donors for whom 6-month outcome data were available and compared patient and graft survival, kidney delayed graft function (DGF), and biliary complications between TA-NRP DCD and SRR DCD organ recipients. Patient and graft survival did not differ significantly between groups for either kidney or liver recipients. Significantly fewer TA-NRP kidney recipients developed DGF (12.7% [15/118] vs 42.0% [84/200], P <.001), and TA-NRP and pumped kidneys had lower odds for DGF on multivariate analysis. No liver recipients in either group had biliary complications or were relisted for transplantation for ischemic cholangiopathy. Although long-term outcomes need to be investigated, our early results show similar outcomes for recipients of TA-NRP DCD abdominal organs versus recipients of SRR DCD abdominal organs. We believe that TA-NRP is an effective approach to expand the use of DCD organs.

(69) Thoracoabdominal Normothermic Regional Perfusion Does Not Adversely Impact Early Outcomes in Donation after Circulatory Death Lung Transplantation

(69) Thoracoabdominal Normothermic Regional Perfusion Does Not Adversely Impact Early Outcomes in Donation after Circulatory Death Lung Transplantation

(871) Cytokine Profiles During Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP) in a Porcine Model

(871) Cytokine Profiles During Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP) in a Porcine Model

(463) One-year Outcome in a Patient Who Underwent Three Organ Transplant Using Thoracoabdominal Normothermic Regional Perfusion (ta-nrp) for Al- Amyloidosis

(463) One-year Outcome in a Patient Who Underwent Three Organ Transplant Using Thoracoabdominal Normothermic Regional Perfusion (ta-nrp) for Al- Amyloidosis

(614) Protecting the Heart Prior to Onset of Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP)

(614) Protecting the Heart Prior to Onset of Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP)

Early United States experience with lung donation after circulatory death using thoracoabdominal normothermic regional perfusion

Thoracoabdominal normothermic regional perfusion (TA-NRP) has recently begun being utilized in the United States for recovery of cardiothoracic allografts from some donors after circulatory death (DCD), but data on lungs recovered in this method is limited to case reports. We conducted a national retrospective review of lung transplants from DCD donors recovered using TA-NRP. Of the 434 total DCD lung transplants performed between January 2020 and March 2022, 17 were recovered using TA-NRP. Compared to direct recovery DCD transplants, recipients of TA-NRP DCD transplants had lower likelihood of ventilation >48 hours (23.5% vs 51.3%, p=0.027) and similar likelihood of predischarge acute rejection, requirement for extracorporeal membrane oxygenation at 72 hours, hospital lengths of stay, and survival at 30, 60, and 90 days post-transplant. These early data suggest that DCD lung recovery using TA-NRP might be a safe way to further expand the donor pool and warrant further study.

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

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. 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. 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). 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. None of the authors have a financial relationship with a commercial entity that has an interest in the subject.

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs

The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p=0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p=0.24 and 0.79 respectively). Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.

Donation after circulatory death heart transplantation using normothermic regional perfusion:The NYU Protocol.

This study aimed to evaluate the impact of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion on the metabolic milieu of donation after cardiac death organ donors before transplantation. Local donation after cardiac death donor offers are assessed for suitability and willingness to participate. Withdrawal of life-sustaining therapy is performed in the operating room. After declaration of circulatory death and a 5-minute observation period, the cardiac team performs a median sternotomy, ligation of the aortic arch vessels, and initiation of thoraco-abdominal normothermic regional perfusion via central cardiopulmonary bypass at 37 °C. Three sodium chloride zero balance ultrafiltration bags containing 50 mEq sodium bicarbonate and 0.5g calcium carbonate are infused. Arterial blood gas measurements are obtained every 15 minutes after every zero balance ultrafiltration bag is infused, and blood is transfused as needed to maintain hemoglobin greater than 8 mg/dL. Cardiopulmonary bypass is weaned with concurrent hemodynamic and transesophageal echocardiogram evaluation of the donor heart. The remainder of the procurement, including the abdominal organs, proceeds in a similar controlled fashion as is performed for a standard donation after brain death donor. Between January 2020 and May 2022, 18 donation after cardiac death transplants using the thoraco-abdominal normothermic regional perfusion protocol were performed at our institution. The median donor age was 42.5 years (range, 20-51 years), and 88.9% (16/18) were male. The mean total donor cardiopulmonary bypass time was 88.8 ± 51.8 minutes. At the beginning of cardiopulmonary bypass, the average donor lactate was 9.4 ± 1.5 mmol/L compared with an average final lactate of 5.3 ± 2.7 mmol/L (P<.0001). The average beginning potassium was 6.5 ± 1.8 mmol/L compared with an average end potassium of 4.2 ± 0.4 mmol/L (P<.0001) . The average beginning hemoglobin was 6.8 ± 0.7 g/dL, and the average end hemoglobin was 8.2 ± 1.3 g/dL (P<.001) . On average, donation after cardiac death donors received transfusions of 2.3 ± 1.5 units of packed red blood cells. Of the 18 donors who underwent normothermic regional perfusion, all hearts were deemed suitable for recovery and successfully transplanted, a yield of 100%. Other organs successfully recovered and transplanted include kidneys (80.6% yield), livers (66.7% yield), and bilateral lungs (27.8% yield). The use of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion is a burgeoning option for improving the quality of organs from donation after cardiac death donors. Meticulous intraoperative management of donation after cardiac death donors with a specific focus on improving their metabolic milieu may lead to improved graft function in transplant recipients.

Heart-liver-kidney transplantation for AL amyloidosis using normothermic recovery and storage from a donor following circulatory death: Short-term outcome in a first-in-world experience

AL amyloidosis is a rare condition characterized by the overproduction of an unstable free light chain, protein misfolding and aggregation, and extracellular deposition that can progress to multiorgan involvement and failure. To our knowledge, this is the first worldwide report to describe triple organ transplantation for AL amyloidosis and triple organ transplantation using thoracoabdominal normothermic regional perfusion recovery with a donation from a circulatory death (DCD) donor. The recipient was a 40-year-old man with multiorgan AL amyloidosis with a terminal prognosis without multiorgan transplantation. An appropriate DCD donor was selected for sequential heart, liver, and kidney transplants via our center's thoracoabdominal normothermic regional perfusion pathway. The liver was additionally placed on an ex vivo normothermic machine perfusion, and the kidney was maintained on hypothermic machine perfusion while awaiting implantation. The heart transplant was completed first (cold ischemic time [CIT]: 131 minutes), followed by the liver transplant (CIT: 87 minutes, normothermic machine perfusion: 301 minutes). Kidney transplantation was performed the following day (CIT: 1833 minutes). He is 8 months posttransplant without evidence of heart, liver, or kidney graft dysfunction or rejection. This case highlights the feasibility of normothermic recovery and storage modalities for DCD donors, which can expand transplant opportunities for allografts previously not considered for multiorgan transplantations.

CDCDD-NRP is consistent with US legal standards for determining death

Donation after circulatory determination of death (DCDD) has increased organ donation rates in the US over the past decade within an established legal framework, which is consistent with and supports individual and family decisions regarding organ donation in the context of end-of-life care. A new application, controlled DCDD donation utilizing thoracoabdominal normothermic regional perfusion (NRP) protocols (cDCDD-NRP), provides the opportunity to maximize a donation decision by recovering additional organs for transplant, including the heart, and to limit the detrimental impact of warm ischemic time by perfusing organs in situ following the declaration of circulatory death. In this viewpoint, we narrate our rationale for why cDCDD-NRP is consistent within the existing legal framework for organ donation in the United States and recommend no changes to the Uniform Determination of Death Act.

Lung transplantation following donation after circulatory death

• Lung transplantation, a potentially life-saving therapy, remains significantly limited due to donor organ availability. • Donation after Circulatory Death (DCD) is a promising clinical endeavor that may increase the donor pool for viable organs with successful post-transplant outcomes. • The clinical setting and circumstances surrounding DCD are important in successful recovery. • Controlled DCD lung transplantation has success rates similar to lung transplantation following Donation after Brain Death (DBD). • The evolving application of extracorporeal circulation technology, both the ex vivo lung perfusion (EVLP) modality as well as the more recent thoracoabdominal normothermic regional perfusion (TA-NRP), could have a leading role in the optimization of DCD transplants soon.

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.

Normothermic Regional Perfusion is an Emerging Cost-Effective Alternative in Donation After Circulatory Death (DCD) in Heart Transplantation.

In donation after circulatory death (DCD) organ transplantation, normothermic regional perfusion (NRP) restores oxygenated blood flow following cardiac arrest and reverses warm ischemia. Recently, NRP has also been used to help recover DCD hearts in addition to the abdominal organs. While DCD donation has increased the number of abdominal organs and lungs pool, it has not been able to increase the number of heart transplants, despite the fact that it has the potential to increase the number of heart transplants by 15-30%. Thoracoabdominal normothermic regional perfusion makes heart transplantation feasible and permits assessing heart function before an organ procurement without affecting the preservation of abdominal organs. NRP can be used in two ways for DCD donor heart transplants: normothermic regional perfusion followed by machine perfusion (NRP-MP) and normothermic regional perfusion followed by static cold storage (NRP-SCS). Normothermic regional perfusion is an emerging technology, a cost-effective alternative in donation after circulatory death (DCD), and will increase the pool of donors in heart transplantation.

Regarding normothermic regional perfusion: Arguing by insistence is not a strong argument

Regarding normothermic regional perfusion: Arguing by insistence is not a strong argument

High Oxygenation During Normothermic Regional Perfusion After Circulatory Death Is Beneficial on Donor Cardiac Function in a Porcine Model.

Thoracoabdominal normothermic regional perfusion (NRP) is a new method for in situ reperfusion and reanimation of potential donor organs in donation after circulatory death by reperfusion of the thoracic and abdominal organs with oxygenated blood. We investigated effects of high oxygenation (HOX) versus low oxygenation (LOX) during NRP on donor heart function in a porcine model. Pigs (80 kg) underwent a 15-min anoxic cardiac arrest followed by cardiac reanimation on NRP using a heart-lung bypass machine with subsequent assessment 180 min post-NRP. The animals were randomized to HOX (FiO2 1.0) or LOX (FiO2 0.21 increased to 0.40 during NRP). Hemodynamic data were obtained by invasive blood pressure and biventricular pressure-volume measurements. Blood gases, biomarkers of inflammation, and oxidative stress were measured. Eight of 9 animals in the HOX group and 7 of 10 in the LOX group were successfully weaned from NRP. Right ventricular end-systole elastance was significantly improved in the HOX group compared with the LOX group, whereas left ventricular end-systole elastance was preserved at baseline levels. Post-NRP cardiac output, mean arterial, central venous, and pulmonary capillary wedge pressure were all comparable to baseline. Creatinine kinase-MB increased more in the LOX group than the HOX group, whereas proinflammatory cytokines increased more in the HOX group than the LOX group. No difference was found in oxidative stress between groups. All hearts weaned from NRP showed acceptable hemodynamic function for transplantation. Hearts exposed to LOX showed more myocardial damage and showed poorer contractile performance than hearts reperfused with high oxygen.