Direct Comparison of NRP With DHOPE and COR-NMP to Maximize the Use of ECD After DCD Donation in the Netherlands

The persistent discrepancy between the number of patients awaiting liver transplant and the availability of liver grafts. In the Netherlands, still, 1 in 5 either dies on the waiting list or is removed from the waiting list due to deterioration of the disease. To increase the supply of suitable liver grafts, extended-donor criteria allografts can be used. Extended criteria donors (ECD) include older donors, donors with fatty livers, donors with high transaminase levels and donor after circulatory death (DCD). However, because of an inevitable longer period of warm ischemia, DCD livers have increased risk of primary non function and biliary complications, resulting in either patient morbidity, re-transplantation or patient death. Due to uncertainty of the effect of the longer ischemia time on their quality, DCD grafts can be accepted with reluctance or even discarded.

The persistent organ shortage has forced transplant programs to explore options to expand the organ supply. Parallel to this, interest in use of extended criteria donors (ECD) livers drove an evolution in current technique to retrieve, preserve and improve livers before transplantation. Before the era of perfusion, the organs were retrieved by using standard rapid retrieval (SRR) and preserved by static cold storage (SCS). In 1930 researchers have explored machine perfusion as a technique to preserve organs, but nowadays this technique has many more potentials including testing and improving. Currently, there is a wide diversity in different perfusion techniques, varying from in vivo to ex vivo and hypothermic (8-12°C) to normothermic (35-37°C). The rationale behind perfusion is to restore the flow through the organs with a pump to provide oxygen and drugs.

In normothermic regional perfusion (NRP) the physiological abdominal circulation is simulated with in vivo, normothermic, oxygenated perfusion during the first two hours after circulatory death. NRP replaces SRR, because this techniques allows a surgeon to retrieve the organs in a longer timeframe during this perfusion. Also, NRP can reverse early ischemia, reduce ischemic type biliary lesions, prevent surgical damage due to a more relax operation and the potential to test organs. The possibility to test the organ during NRP enables a save environment to transplant livers from older DCD donors above 60 years old. , In many countries, NRP is obligatory in DCD donation, however this is not the current golden standard in the Netherlands. Only in the Dutch Western region the livers of donors after circulatory death (Maastricht type III and V) above 50 years old will undergo NRP.

Independently of age or region, all DCD livers in the Netherlands will undergo dual hypothermic oxygenated perfusion (DHOPE) in the receiving hospital. DHOPE is a dual (through both portal vein and hepatic artery) hypothermic, ex vivo, machine perfusion technique, which depends on the presence of sufficient oxidative mitochondrial metabolism.

subsequentially, oxygenated mitochondria metabolize due to ischemia accumulated succinate and recharge adenosine tri-phosphate, which leads to less reactive oxygen species, less danger signaling and to reduced overall downstream inflammation during later normothermic reperfusion at implantation. , In comparison with SCS, DHOPE has a significant reduction in postreperfusion syndrome, early allograft dysfunction, and non-anastomotic strictures after DCD. For this reason, this perfusion technique is incorporated in the Dutch national protocol for all DCD liver grafts and financed by personal health insurances. High risk donor livers or livers from donors above sixty years old in the Northeastern region will additionally undergo controlled oxygenated rewarming normothermic machine perfusion (COR-NMP) after DHOPE. Normothermic ex vivo machine perfusion has the opportunity to test ECD grafts before transplant. The controlled oxygenated rewarming prevents sudden temperature shifts and subsequentially reduces ischemia reperfusion injury.