Association of procurement technique with organ yield and cost following donation after circulatory death.

Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Cost effectiveness of commercial portable ex vivo lung perfusion at a low-volume US lung transplant center.

BACKGROUND: Portable ex vivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of ex vivo lung perfusion at a low-volume lung transplant center in the USA. METHODS: Patients listed for lung transplantation (2015-2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. RESULTS: Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky-adjusted life year gained by ex vivo lung perfusion was 1.00-1.72 times more expensive. CONCLUSIONS: Portable ex vivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.

Social, economic, and policy implications of organ preservation advances.

PURPOSE OF REVIEW: Despite over 60 years of progress in the field of since the first organ transplant, insufficient organ preservation capabilities still place profound constraints on transplantation. These constraints play multiple and compounding roles in the predominant limitations of the field: the severe shortages of transplant organs, short-term and long-term posttransplant outcomes and complications, the unmet global need for development of transplant infrastructures, and economic burdens that limit patient access to transplantation and contribute to increasing global healthcare costs. This review surveys ways that advancing preservation technologies can play a role in each of these areas, ultimately benefiting thousands if not millions of patients worldwide. RECENT FINDINGS: Preservation advances can create a wide range of benefits across many facets of organ transplantation, as well as related areas of transplant research. As these technologies mature, so will the policies around their use to maximize the benefits offered by organ preservation. SUMMARY: Organ preservation advances stand to increase local and global access to transplantation, improve transplant outcomes, and accelerate progress in related areas such as immune tolerance induction and xenotransplantation. This area holds the potential to save the healthcare system many billions of dollars and reduce costs across many aspects of transplantation. Novel preservation technologies, along with other technologies facilitated by preservation advances, could potentially save millions of lives in the coming years.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.

Combination of Euro-Collins and University of Wisconsin Solution: An Effective and Economic Substitute for Organ Procurement.

PURPOSE: Many types of preservation fluid were used in liver procurement. Undoubtedly, the gold standard is the University of Wisconsin (UW) solution. But the solution is expensive. The aim of this study was to evaluate the results of combined acetated Ringer solution, Euro-Collins solution, and UW solution. MATERIALS AND METHODS: All patients undergoing adult liver transplantation from cadaveric donor during January 2013 to December 2017 in King Chulalongkorn Memorial Hospital were included in this study. Donor and recipient characteristics, preservation fluid, operative data, and postoperative outcomes were recorded. RESULTS: A total of 102 patients receiving liver transplants were enrolled into the study. The mean age of donors was 34.2 years. The mean total ischemic time was 420.93 minutes. In recipients, posttransplantation complications were the following: (1) primary nonfunction in 1 patient (0.98%); (2) early allograft dysfunction in 23 patients (22.5%); (3) hepatic artery thrombosis in 3 patients (2.7%); (4) hepatic venous outflow obstruction in 2 patients (1.96%); (5) biliary leakage in 1 patient (0.98%); (6) biliary anastomosis stenosis in 4 patients (3.92%); and (7) biliary nonanastomosis stenosis in 1 patient (0.98%). No inhospital mortality was occurred. Overall mortality rate is 7.8% (8/102). One-, 3-, and 5-year survival were 95.9%, 91.5%, and 88.4%, respectively. CONCLUSIONS: The combination of acetated Ringer solution, Euro-Collins solution, and UW solution is effective and economic for liver preservation. Further study should be conducted.

Long term medical and economical benefit of machine perfusion (MP) kidney storage in comparison to cold storage (CS).

BACKGROUND: Despite documented positive effect of MachinePerfusion (MP) on long-term kidneys-graft function its wide use is restricted due to higher costs. The aim of this study was to analyze the difference in costs of kidney transplantation in patients who received organ stored in ColdStorage (CS) vs those who received kidneys stored with MP.
MATERIAL/METHODS: Analysis was done on kidney transplantations performed between 1994-1999 in 415 patients.. Kidneys were not randomized to MP or to CS: 188 kidneys were stored in CS, 227-in MP. Recipients didn't differ in regard to the age, sex, PRA, HLA mismatch, and immunosupression.The costs of organ procurement,transportation,surgical and anesthetic procedures, episodes of acute rejection were similar for both group of patients and were not included into the analysis. Costs of first month post-transplantation included: the cost of MP, post-transplantation hemodialysis, costs of hospitalization.Analysis of costs difference in between two groups of patients during follow-up included the costs of immunosupression and the monthly cost of dialysis. Statistical analysis was done using linear regression model.
RESULTS: Long graft survival was 68,2% in MP group vs.54,2% in CS group (p=0.02) Return to dialysis treatment was 20% in MP group vs.36% in CS group (p=0.01).Since 2 month post-transplant, mean cost of treatment for one patient was higher of 59,7 USD in CS group vs. MP group (p<0.001)in each month. Costs of investments on MP were equalized in 16 month post-transplantation.
CONCLUSIONS: Despite higher costs of MP use in the first month post transplantation, it is money-saving method of kidneys preservation and its cost of use, are equalized after 16 months post transplantation.

A modified CZ-1 preserving solution for organ transplantation: comparative study with UW preserving solution.

BACKGROUND: The University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution. METHODS: A series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied. RESULTS: There was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22 - 31 hours were transplanted successfully and the mean renal function recovery time was (3.83 +/- 1.68) days. CONCLUSIONS: CZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.

A Cost-Effectiveness Analysis of Organ Preservation Methods for Deceased Donor Kidneys at High Risk for Delayed Graft Function in Brazil.

The clinical benefit of machine perfusion (MP) was recently assessed in a 1-year Brazilian multicenter prospective randomized trial, that showed that the use of MP was associated with a reduced incidence of delayed graft function (DGF) compared to static cold storage (SCS) in kidney transplant recipients (45% vs 61%). The objective of the present analysis is to consider the cost-effectiveness of MP relative to SCS based on clinical data from this Brazilian cohort. A decision tree model was constructed to simulate a population of 1000 kidney transplant recipients based on data derived from this Brazilian multicenter clinical trial. The model accounts for different health state utilities to estimate the cost-effectiveness of deceased donor kidney transplantation in Brazil comparing 2 kidney preservation methods: MP and SCS. The model accounts for 3 possible graft outcomes at 1 year post-transplantation: success (an immediate functioning kidney), failure (primary nonfunction requiring a return to dialysis), or DGF 1 year post-transplant. MP provided 612 total quality-adjusted life years (QALYs) (0.61 QALYs per patient) as compared to SCS (553 total QALYs, 0.55 QALYs per patient). MP was cost effective relative to SCS (US$22,117/QALY, R$70,606/QALY). The use of MP also resulted in more functioning grafts than SCS (821 vs 787), leading to a cost per functioning graft of US$38,033 (R$121,417). In conclusion, this analysis indicates that, despite the initial added cost associated with MP, the use of MP results in more functioning grafts (821 vs 787) and higher patient quality of life relative to SCS in Brazil.

Survival extrapolation using the poly-Weibull model.

Recent studies of (cost-) effectiveness in cardiothoracic transplantation have required estimation of mean survival over the lifetime of the recipients. In order to calculate mean survival, the complete survivor curve is required but is often not fully observed, so that survival extrapolation is necessary. After transplantation, the hazard function is bathtub-shaped, reflecting latent competing risks which operate additively in overlapping time periods. The poly-Weibull distribution is a flexible parametric model that may be used to extrapolate survival and has a natural competing risks interpretation. In addition, treatment effects and subgroups can be modelled separately for each component of risk. We describe the model and develop inference procedures using freely available software. The methods are applied to two problems from cardiothoracic transplantation.

Pancreas preservation with University of Wisconsin and Celsior solutions: a single-center, prospective, randomized pilot study.

BACKGROUND: Celsior is an extracellular-type, low-viscosity, preservation solution already used for heart, lung, liver, and kidney transplantation. We report the results of a single-center, prospective, randomized pilot study specifically designed to compare the safety profile of Celsior solution with University of Wisconsin (UW) solution in clinical pancreas transplantation. METHODS: A total of 105 consecutive procurements were randomized to graft preservation with UW (n=53) solution or Celsior (n=52) solution. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Five grafts were discarded and 100 grafts (50 UW vs. 50 Celsior) were transplanted. Mean cold and warm ischemia times were 11.0 +/- 2.1 hr and 37.2 +/- 6.0 min for UW compared with 10.8 +/- 1.8 hr and 38.1 +/- 5.9 min for Celsior (P =not significant). Delayed endocrine pancreas function was recorded in one graft preserved with UW solution. Eleven recipients (UW 12% vs. Celsior 10%, P =not significant) required a relaparotomy. The mean serum levels of glucose, amylase, and lipase remained comparable between the study arms at equivalent intervals after transplantation. One recipient died with functioning grafts in each study arm; two further grafts were lost to arterial thrombosis (Celsior) and chronic rejection (UW), respectively. Actuarial 1-year patient and graft survival rates overlapped in the two study arms (98% and 96%, respectively). CONCLUSIONS: Within the range of cold ischemia time reported in this study, UW and Celsior solutions have similar safety profiles for pancreas preservation.

The cost-effectiveness of preservation with UW and EC solution for use in cadaveric kidney transplantation in the case of single kidney donors.

University of Wisconsin (UW) solution is now commonly used as a single-flush solution during multiorgan procurement for effective preservation of all intraabdominal organs including the kidney. Many kidneys from single kidney donors are still preserved in Eurocollins solution and the question is whether preservation in UW solution is more cost-effective. A European randomized multicenter trial was organized by the Department of Surgery of Leiden University in close cooperation with Eurotransplant to study the efficacy of UW solution as compared with EC solution. On the basis of this trial we found that at three months after transplant 92.4% of the patients in the UW group had a functioning graft in comparison with 88.4% in the EC group (similar figures after one year were 88.2% and 82.5%, P approximately 0.04), while health care expenditure during these first three months was on average US$ 700 lower for the UW group than for the EC group, taking into account the price difference in the preservation fluids. The long-term benefits of using UW solution as compared with EC solution were conservatively estimated at US$ 7000 per patient reflecting the additional expenses for dialysis in the EC group. We concluded that the extra costs of using UW solution instead of EC solution (US$ 230 per kidney) can be easily earned back within three months and that the long-term savings of such a strategy are considerable. Moreover, the health status of patients in the UW group is expected to be better on the average than in the EC group. Simply reacting to the price tag of the UW solution may be penny-wise but pound-foolish.

A rapid, simple, and cost-effective method for screening liver preservation solutions in the rat.

BACKGROUND: Rat liver transplantation models or isolated liver perfusion models are currently used for assessing efficacy of liver preservation methods. We tested the hypothesis that hepatocellular enzymes released into the washout solution after preservation may predict hepatic function during reperfusion and could thus be alternatively used for evaluating efficiency of liver preservation solutions. Furthermore, we applied this approach for assessing the role of Kupffer cells (KC) in preservation-induced liver damage. METHODS: After preservation in University of Wisconsin (UW) or Euro-Collins (EC) solution, rat livers were washed with Ringer-lactate solution. Correlations between enzymes released into the washout solution and hepatocyte functional parameters determined during reperfusion on using a blood-free perfusion model were investigated. RESULTS: In UW-preserved livers, acid phosphatase (ACP) activity correlated negatively with bile flow (R = -0.904), taurocholate intrinsic clearance (R = -0.841), and bromosulfophthalein excretion (R = -0.831). Both alanine transaminase and aspartate transaminase activities correlated with the functional parameters investigated. In EC-stored livers, correlation was also found between ACP activity and bile flow (R = -0.666). Livers stored in UW solution exhibited approximately 3 times lower washout activities of enzymes studied than livers stored in EC solution. Mitochondria isolated from UW-stored livers exhibited significantly better function than those isolated from EC-stored livers. Blockade of KC did not influence enzyme release into the washout solution. CONCLUSIONS: Determination of ACP, alanine transaminase, and aspartate transaminase activities in the washout solution can be used as a rapid, simple, and cost-effective way for screening liver preservation solutions. The results also suggest that KC were not involved in preservation-induced liver damage.

Donor blood perfusion improves myocardial recovery after heart transplantation.

BACKGROUND: Improved methods of donor heart preservation may allow for prolonged storage and permit remote procurement. Previous attempts to use oxygenated perfusion circuits during storage have not gained widespread acceptance because they were either too impractical or complicated to use for remote harvest. We hypothesized that collection and perfusion of donor blood during prolonged storage may improve myocardial recovery. Our aim was to devise a safe, simple, cost-effective system that could be used in any hospital setting. METHODS: Yorkshire pigs (40 to 50 kg) were used to perform 16 orthotopic heart transplantations with either continuous perfusion with donor blood (BL, n = 8) or standard hypothermic storage (CON, n = 8). After administration of heparin, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2688 +/- 166 ml) was harvested in the BL group. After filtration for particulate matter, blood perfusion was initiated via a standard intravenous transfusion apparatus at room temperature (20 degrees C) and a pressure of 60 mm Hg and maintained during storage. Arterial and coronary sinus blood samples were obtained to examine myocardial oxygen extraction, lactate release, and acid production. A Millar micromanometer was used to measure left ventricular developed pressures at an end-diastolic pressure of 2 and 10 mm Hg both before and after transplantation. RESULTS: All pigs (eight of eight) in the BL group were successfully weaned off bypass compared to three of eight in the CON group (p < 0.01). Developed pressures (at left ventricular end-diastolic pressure = 10 mm Hg) was improved in the BL group (mean +/- SD: baseline: BL: 90 +/- 16 mm Hg vs CON: 83 +/- 12 mm Hg, p = NS; posttransplantation: BL: 66 +/- 8 mm Hg vs CON: 35 +/- 29 mm Hg, p < 0.05). Similarly, maximum dP/dt was higher in the BL group. Lactate release was higher at cross-clamp removal in the BL group (2.4 +/- 0.3 mmol/L vs 0.7 +/- 0.2 mmol/L, p < 0.01). There were no differences in oxygen extraction or acid production during reperfusion. CONCLUSIONS: Perfusion of donor blood improved the ability to wean off bypass after 4 hours of storage. Blood perfusion permitted persistent myocardial metabolism during the ischemic period, which led to improved functional recovery. Harvesting donor blood for subsequent perfusion during prolonged storage may improve the results of orthotopic heart transplantation and allow for more distant procurement of donor organs.

Organ preservation.

Our clinical transplantation results have been very satisfying, with about 90% graft survival after 1 year. Currently, preservation of the liver, pancreas, and kidney, although not ideal, appears to meet all our clinical needs. Improvements in heart and lung preservation are needed and will result in increasing the number of cadaveric organs available for patients with end-stage intrathoracic organ diseases. In the future, machine perfusion may become the standard method for organ preservation for most organs because of the excellent preservation results and long-term preservation achieved.

[Costs of preserved corneal transplants]. / Kosten gelagerter Hornhauttransplantate.

BACKGROUND: Organ culture medium and Optisol are the most commonly used corneal storage mediums. This study compares the costs for these two methods. METHODS: In the calculation of costs we did not just take the direct costs into account, but also tried to determine the fixed costs per transplanted cornea with corresponding assumptions. RESULTS: Proceeding on the assumption that 50 stored corneas were transplanted per year, an amount of 11,660 ATS (1,666 DM, 857 ECU) for each organ cultured and 11,986 ATS (1,712 DM, 881 ECU) for each graft preserved in Optisol was calculated. Raising the number of transplanted corneas to 400 per year, each tissue stored in organ culture medium costs 2,811 ATS (402 DM, 207 ECU) and those preserved in Optisol 3234 ATS (462 DM, 238 ECU). CONCLUSION: Since organ culture storage gives us a reduction in costs of more than 15% compared to storing in Optisol, when preserving 400 transplantable grafts, from the business economics aspect, this storage method should be preferred.

[Umbilical cord blood as a biological spare part. Experiences from a pilot project] at the Fredericia hospital]. / Navlesnorsblod som biologisk reservedel. Erfaringer med et pilotprojekt ved Fredericia Sygehus.

The haematopoietic stem cells remaining in the placenta after the umbilical cord has been cut can substitute for bone marrow in transplantations. It is argued that these cells should be retrieved and kept frozen as the child's personal biological spare part. A pilot, population-based collection of cord blood was carried out in a small provincial in Denmark. It was found that the pregnant women supported the concept (89%), that the midwives and technicians could carry out sampling and freezing after a short instruction period, and that the cost of sampling and storing for 75 years approx. DKK 12,000 per child. The project group is now seeking partners for further development of the concept.