Abdominal Regional Perfusion in Donation After Cardiac Death for Multi-Organ Transplantation

Liver Transplantation and Limitations of DCD Transplantation:

Liver transplantation (LT) is the sole curative therapy for end stage liver disease and has emerged as the treatment of choice for hepatocellular carcinoma. Recent evidence has also demonstrated efficacy in a growing number of malignancies including intra/extra-hepatic cholangiocarcinoma, metastatic neuro-endocrine tumors, and colorectal liver metastases. Despite these advantages, LT is limited by the availability of suitable donor organs resulting in lengthened LT waitlist times. However, during this waiting period patients may deteriorate making them ineligible for LT. In the US, 16,000 patients are listed for LT, and approximately 2000 die annually while waiting for suitable organs. In 2017, over 500 Canadians were on a waiting list for LT and nearly 200 died or withdrew from the transplant list while waiting. Additionally, while LT secondary to hepatitis C is declining, nonalcoholic steatohepatitis, alcoholic liver disease and transplant oncology indications are growing, increasing the overall demand for liver transplant.

One strategy to expand the donor pool has been to optimize utilization of organs from donation after cardiac death (DCD). While outcomes of DCD kidney, pancreas and lung transplants show similar patient and graft survival to donation after brain death (DBD) transplants, DCD livers have worse patient and graft survival, higher complications, and costs, along with worse quality of life. DCD liver grafts have twice the rate of early complications including primary non-function (PNF) and early allograft dysfunction (EAD). EAD is a transient condition with the potential for graft function recovery whereas PNF is a more severe complication leading to graft failure requiring emergency re-transplantation. In the long term, the use of DCD liver allografts is associated with a 10 fold increase in biliary complications, typically resulting in graft loss or death. Moreover, there is a high cost associated with complications and readmissions following LT, which can be upwards of $50,000 per patient. Studies investigating factors contributing to these costs have revealed that DCD allografts had the greatest impact on transplant costs. Consequently, initial enthusiasm for the use of DCD livers for LT has waned such that utilization is restricted to only ideal DCD livers from younger donors with short warm and cold ischemia times. Developing methodologies to reduce the complications associated with DCD organs and improve overall outcomes would have an immense impact on the lives of transplant patients while concurrently reducing costs on the healthcare system.

Abdominal Regional Perfusion and Limitations of Normothermic Machine Perfusion:

Conventional DCD recovery utilizes a rapid recovery technique which flushes abdominal organs with cold preservation solution to slow cellular metabolism and evacuate blood/clots to preserve the integrity of the microvasculature. This is preceded by the agonal phase between withdrawal of life support and cessation of cardiac function. During this period, abdominal organs are subject to warm ischemia resulting in accumulation of toxic metabolites, depletion of intracellular energy and anti-oxidant stores, leading to exacerbation of ischemia reperfusion at the time of implantation.