Abdominal Normothermic Regional Perfusion Research Articles

US Liver Transplant Outcomes After Normothermic Regional Perfusion vs Standard Super Rapid Recovery

Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. cDCD livers were recovered by either NRP or SRR. The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

(915) - UK Experience of Direct Procurement of Lungs with Ongoing Abdominal Normothermic Regional Perfusion from Controlled DCD Donors

(915) - UK Experience of Direct Procurement of Lungs with Ongoing Abdominal Normothermic Regional Perfusion from Controlled DCD Donors

Stepwise development and expansion of an abdominal normothermic regional perfusion program for donation after circulatory determination of death organ procurement.

Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US. We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras. In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization. The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.

Abdominal normothermic regional perfusion in the United States: current state and future directions.

Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. Liver and kidney transplantation from thoracoabdominal NRP (TA-NRP) donors in the United States was found to have lower rates of delayed kidney graft function and similar graft and patient survival versus recipients of cardiac super rapid recovery (SRR) DCD donors. The excellent outcomes with NRP have prompted the expansion of NRP technology to abdominal transplant programs. Excellent early outcomes with liver and kidney transplantation have prompted the growth of NC-NRP procurement for abdominal-only DCD donors across the US, and now requires standardization of technical and nontechnical aspects of this procedure.

Technique of blood conservation in direct perfusion and procurement of lungs in combination with abdominal normothermic regional perfusion

Utilization of abdominal normothermic regional perfusion (A-NRP) for organ procurement in donation after circulatory death (DCD) is becoming a commonplace. Simultaneous procurement of the donor lungs is technically challenging due to blood loss in the chest leading to inadequate circulatory support to the abdominal organs. We describe a priority-based stepwise approach to minimise blood loss in the chest and conserve blood that can be utilized for the A-NRP.

Procurement of heart and heart-lungs block with simultaneous abdominal normothermic regional perfusion

Procurement of heart and heart-lungs block with simultaneous abdominal normothermic regional perfusion

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.

Outcomes of liver transplantation with thoracoabdominal normothermic regional perfusion: a matched-controlled initial experience in Spain

Thoracoabdominal (TA) normothermic regional perfusion (NRP) should allow the safe recovery of heart and liver grafts simultaneously in the context of controlled donation after circulatory death (cDCD). We present the initial results of cDCD liver transplantation with simultaneous liver and heart procurement in Spain until October 2021. Outcomes were compared with a matched cohort of cDCD with abdominal NRP (A-NRP) from participating institutions. Primary endpoints comprised early allograft dysfunction (EAD) or primary non-function (PNF), and the development of ischemic-type biliary lesions (ITBL). Six transplants were performed using cDCD with TA-NRP during the study period. Donors were significantly younger in the TA-NRP group than in the A-NRP group (median 45.6 years and 62.9 years respectively, p = 0.011), with a median functional warm ischemia time of 12.5 min in the study group and 13 min in the control group. Patient characteristics, procurement times, and surgical baseline characteristics did not differ significantly between groups. No patient in the study group developed EAD or PNF, and over a median follow-up of 9.8 months, none developed ITBL or graft loss. Extending A-NRP to TA-NRP for cardiac procurement may be technically challenging, but it is both feasible and safe, showing comparable postoperative outcomes to A-NRP.

310.1: Improved pancreatic islet isolation yield after abdominal normothermic regional perfusion of controlled donation after circulatory death donors

310.1: Improved pancreatic islet isolation yield after abdominal normothermic regional perfusion of controlled donation after circulatory death donors

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.

Viability assessment of livers donated after circulatory determination of death during normothermic regional perfusion.

Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP. To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2  = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2 ) and VO2 . Lactate clearance was correlated to transaminase levels and DO2 -normalized lactate clearance was the parameter best discriminating between study groups. DO2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP.

Extended criteria liver donation after circulatory death with prolonged warm ischemia: a pilot experience of normothermic regional perfusion and no subsequent ex-situ machine perfusion

BackgroundLivers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. MethodsProspectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. ResultsThe median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. ConclusionsThis pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.

Complex use of perfusion techniques in kidney transplantation from a donor with out-of-hospital cardiac arrest (clinical case)

Objective: to present the successful experience with a donor with out-of-hospital cardiac arrest (OHCA) in whom a set of modern perfusion techniques was used to obtain kidneys suitable for transplantation.Materials and methods. Automatic chest compression was resumed in an OHCA donor (after biological death has been confirmed in the hospital) to maintain minimal perfusion under mechanical ventilation with 100% FiO2. With femoral vein cannulation, an extracorporeal circuit with a centrifuge pump and oxygenator was connected and abdominal normothermic regional perfusion was initiated. After 215 minutes, kidney was explanted under normothermic machine perfusion. Next, the left kidney was placed in the LifePort Kidney Transporter for hypothermic machine perfusion of donor kidneys. Perfusion time was 285 minutes. The right kidney was transplanted without additional ex-vivo perfusion.Results. Due to the complex use of perfusion techniques both in the donor body and ex-vivo, donor kidneys, after OHCA, with a total warm ischemia time of 110 minutes, were transplanted to recipients with good results. In the postoperative period, there was delayed function of the left and right renal grafts. The patients were discharged in a satisfactory condition under outpatient follow-up.Conclusion. The possibility and efficiency of organ donation after OHCA, facilitated by modern perfusion techniques and devices, open up a new perspective in addressing the organ shortage crisis.

Bronchial Stenosis After Lung Transplantation From cDCD Donors Using Simultaneous Abdominal Normothermic Regional Perfusion: A Single-center Experience.

Controlled donation after circulatory death (cDCD) has increased the number of lung donors significantly. The use of abdominal normothermic regional perfusion (A-NRP) during organ procurement is a common practice in some centers due to its benefits on abdominal grafts. This study aimed to assess whether the use of A-NRP in cDCD increases the frequency of bronchial stenosis in lung transplant (LT) recipients. A single-center, retrospective study including all LTs was performed between January 1, 2015, and August 30, 2022. Airway stenosis was defined as a stricture that leads to clinical/functional worsening requiring the use of invasive monitoring and therapeutic procedures. A total of 308 LT recipients were included in the study. Seventy-six LT recipients (24.7%) received lungs from cDCD donors using A-NRP during organ procurement. Forty-seven LT recipients (15.3%) developed airway stenosis, with no differences between lung recipients with grafts from cDCD (17.2%) and donation after brain death donors (13.3%; P  = 0.278). A total of 48.9% of recipients showed signs of acute airway ischemia on control bronchoscopy at 2 to 3 wk posttransplant. Acute ischemia was an independent risk factor for airway stenosis development (odds ratio = 2.523 [1.311-4.855], P  = 0.006). The median number of bronchoscopies per patient was 5 (2-9), and 25% of patients needed >8 dilatations. Twenty-three patients underwent endobronchial stenting (50.0%) and each patient needed a median of 1 (1-2) stent. Incidence of airway stenosis is not increased in LT recipients with grafts obtained from cDCD donors using A-NRP.

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant: What is the evidence?

The widespread uptake of different machine perfusion (MP) strategies for liver transplant has been driven by an effort to minimize graft injury. Damage to the cholangiocytes during the liver donation, preservation, or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage. This problem continues to trouble clinicians, and may have catastrophic consequences for the graft and patient. Ischemic injury, as a result of compromised hepatic artery flow, is a well-known cause of biliary strictures, sepsis, and graft failure. However, very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions (ITBL) that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise. Both the warm and cold ischemic period duration appear to influence the onset of ITBL. All of the commonly used MP techniques deliver oxygen to the graft cells, and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL. As clinical experience and published evidence grows for these modalities, the impact they have on ITBL rates is important to consider. In this review, the evidence for the three commonly used MP strategies (abdominal normothermic regional perfusion [A-NRP], hypothermic oxygenated perfusion [HOPE], and normothermic machine perfusion [NMP] for ITBL prevention has been critically reviewed. Inconsistencies with ITBL definitions used in trials, coupled with variations in techniques of MP, make interpretation challenging. Overall, the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage. The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

N-acetylcysteine and Reduction of Ischemia-reperfusion Injury in Liver Transplantation.

In the current issue of Transplantation, Jia et al perform a systemic review and meta-analysis looking at the utilization of N-acetylcysteine (NAC) in the donor and recipient in liver transplantation.1,2 It has been suggested that NAC may have a role in mitigating ischemia-reperfusion injury that occurs during the various stages of organ donation. The pathophysiology of ischemia-reperfusion injury is mainly due to the oxidative stress and cytotoxicity arising from the imbalance between oxidants and antioxidants. NAC is a rich source of sulfhydryl groups, which are important for replenishing glutathione (GSH) stores. GSH acts as a free radical scavenger to decrease damage caused by the toxic free radicals. GSH is the main endogenous antioxidant, and the liver is the main organ producing GSH under normal conditions.2 The present meta-analysis demonstrates a lower incidence of primary nonfunction, a reduction in posttransplant peak aspartate transaminase and alanine transaminase, and reduced postoperative complications in the NAC treatment groups compared with the control groups. As a long-time proponent of the use of NAC in the transplant setting, the overall results of this meta-analysis are encouraging. At Mayo Clinic Florida, we routinely use a NAC infusion for donation after circulatory death (DCD) liver transplant recipients. Our protocol involves a bolus of 150 mg/kg given over 1 h before reperfusion followed by an infusion of 150 mg/kg given for 72 h. Our current rate of ischemic cholangiopathy is <4%; however, whether NAC provides any direct benefit in the reduction of ischemic cholangiopathy remains unproven.3 More recently, we have also started using NAC in the perfusate when performing abdominal normothermic regional perfusion in DCD donors ([6 g/30 mL] × 3 vials). Negative effects of NAC administration are minimal. Although the meta-analysis demonstrated a slightly increased need for packed red blood cells and cryoprecipitate in NAC treatment groups, the magnitude of difference was <1 unit. This may imply that although a statistically significant difference was seen, such a small difference may not be clinically significant. There are some limitations to the present study that should be mentioned. One of the challenges with combining the data from the different studies in the present analysis is that some of the studies gave NAC to the donors at the time of donor procurement, some gave NAC to the recipients at the time of transplant, and others gave NAC to both the donor and recipient. Dosing and timing of dosing was also very heterogeneous between the different studies. Given this heterogeneity, developing a comprehensive protocol utilizing NAC is problematic. In the subanalysis, the authors did suggest that NAC administration to the recipient appeared to produce better clinical effects than administration to the donor. Another unanswered question based on the present analysis is how the benefits of NAC may vary by donor type? Some of the studies looked at living donors while others looked at donation after brain death donors and others looked at DCD donors. Could there be a more significant effect in marginal liver grafts with a suspected higher degree of ischemia-reperfusion injury or should NAC be utilized in all cases? Finally postoperative complications were treated as a binary variable (yes/no) for the analysis. Given the vastly different implications of complications based on their severity, using a classification system such as Clavien-Dindo would be more meaningful when comparing study groups. Despite the limitations of the present meta-analysis, the results are encouraging and suggest that NAC does have some potentially beneficial effects in reducing ischemia-reperfusion injury when used in the setting of liver transplantation. The adequate safety of NAC, in addition to its low costs, makes it an appealing intervention. Further studies are needed before evidence is strong enough to recommend a specific protocol describing both optimal timing and dosage for administration. Moreover, the donor type that may achieve the greatest benefit remains unknown.

Development of a portable abdominal normothermic regional perfusion (A-NRP) program in the United States.

In situ abdominal normothermic regional perfusion (A-NRP) has been used for liver transplantation (LT) with donation after circulatory death (DCD) liver grafts in Europe with excellent results; however, adoption of A-NRP in the United States has been lacking. The current report describes the implementation and results of a portable, self-reliant A-NRP program in the United States. Isolated abdominal in situ perfusion with an extracorporeal circuit was achieved through cannulation in the abdomen or femoral vessels and inflation of a supraceliac aortic balloon and cross-clamp. The Quantum Transport System by Spectrum was used. The decision to use livers for LT was made through an assessment of perfusate lactate (q15min). From May to November 2022, 14 A-NRP donation after circulatory death procurements were performed by our abdominal transplant team (N = 11 LT, N = 20 kidney transplants, and 1 kidney-pancreas transplant). The median A-NRP run time was 68 minutes. None of the LT recipients had post-reperfusion syndrome, nor were there any cases of primary nonfunction. All livers were functioning well at the time of maximal follow-up with zero cases of ischemic cholangiopathy. The current report describes the feasibility of a portable A-NRP program that can be used in the United States. Excellent short-term post-transplant results were achieved with both livers and kidneys procured from A-NRP.

(922) Impact of Simultaneous Abdominal Normothermic Regional Perfusion in Lung Transplantation from Controlled Donation after Circulatory Death

(922) Impact of Simultaneous Abdominal Normothermic Regional Perfusion in Lung Transplantation from Controlled Donation after Circulatory Death

Controlled donation after circulatory death lung transplantation: Results of the French protocol including in situ abdominal normothermic regional perfusion and ex vivo lung perfusion

The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT). We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021. One hundred grafts from 14 donor hospitals were accepted by 6 LT centers. The median duration of the agonal phase was 20 minutes [2-166]. The median duration from circulatory arrest to pulmonary flush was 62 minutes [20-90]. Ten lung grafts were not retrieved due to prolonged agonal phases (n=3), failure of NRP insertion (n=5), or poor in situ evaluation (n=2). The remaining 90 lung grafts were all evaluated on EVLP, with a conversion rate of 84% and a cDCD transplantation rate of 76%. The median total preservation time was 707 minutes [543-1038]. Seventy-one bilateral LTs and 5 single LTs were performed for chronic obstructive pulmonary disease (n=29), pulmonary fibrosis (n=21), cystic fibrosis (n=15), pulmonary hypertension (n=8), graft-versus-host disease (n=2), and adenosquamous carcinoma (n=1). The rate of PGD3 was 9% (n=5). The 1-year survival rate was 93.4%. After initial acceptance, cDCD lung grafts led to LT in 76% of cases, with outcomes similar to those already reported in the literature. The relative impacts of NRP and EVLP on the outcome following cDCD LT should be assessed prospectively in the context of comparative studies.