Donation After Cardiac Death Liver Transplantation After More Than 20 Minutes of Circulatory Arrest and Normothermic Regional Perfusion

Donation after cardiac death (DCD) has resurged over the last decade as an additional source to overcome the organ shortage. The main limitation to widespread application of DCD livers is the fact that these organs inevitably sustain warm ischemia damage during circulatory arrest. In Italy, an even greater concern exists about warm ischemia time (WIT), being death for cardiac arrest legally declared on the absence of electrocardiographic activity during a period of 20 minutes, which is much longer when compared with the worldwide practice of 5 minutes. Normothermic regional perfusion (NRP) has been proposed to improve the outcome of DCD transplantation, especially in case of extended WIT and currently plays an important role in DCD kidney transplantation.^1-5 Herein we report the first successful DCD liver transplantation in Italy.

The donor was a 52-year-old man who sustained stroke with consequent severe brain injury not fulfilling the brain death criteria and 2 cardiac arrests, each less than 10 minutes. Clinicians decided not to take further action in case of a new spontaneous circulatory arrest. Given the exceptional nature of the procedure, an ad hoc authorization was obtained from the Italian National Transplant Centre. Consent to donation was previously discussed with the donor's family and formally obtained during the no-touch period. Death was declared after 20 minutes of asystole. Two large-bore cannulae were then placed in the femoral vessels, and a Fogarty balloon catheter was inflated in the supraceliac aorta to isolate the abdominal circulation; this required an additional 15 minutes, making a total of 35 minutes from asystole to NRP. Graft function was monitored for 3 hours of NRP through sequential blood tests (Figure 1A). Liver retrieval followed the standard technique used for brain dead donors, except that cold preservation solution was flushed directly through the femoral cannula.

FIGURE 1: Graft function during NRP and postoperative course. A, Alanine aminotransferase trend during NRP. B, Progressive decline in recipient’s alanine aminotransferase and serum total bilirubin values during hospitalization. ALT, alanine aminotransferase; POD, postoperative day.

The recipient was a 40-year-old man with hepatitis B virus infection and hepatocellular carcinoma. The patient had been adequately informed about marginal organs and accepted this option at the inclusion in the waiting list. A specific informed consent to receive a DCD organ was obtained when the liver was proposed. Overall, cold ischemia time was less than 5 hours. The postoperative course was regular, and the recipient was discharged on postoperative day 17 (Figure 1B). Neither graft rejection nor other complications have been observed after 3 months of ambulatory follow-up. No biliary issues were found at the 3-month T-tube cholangiogram.

Kidneys from the same donor were successfully transplanted in 2 different recipients, within an already well-established local program of DCD kidney transplantation.

Normothermic regional perfusion provides a means of assessing organ viability before transplantation. Numerous evidences exist demonstrating that NRP enables also organ repair on a cellular level. Net and colleagues⁴ showed in a porcine model that NRP after 20 minutes of cardiac arrest converted circulatory arrest into a period of ischemic preconditioning, preparing the organ to cold ischemia. Moreover, NRP permits an unhurried donor operation, minimizing the risk of injury during the procurement.

The key difference between our report and other series is the longer WIT, which includes a no-touch period of 20 minutes before cannulation. This may arise concerns about organ quality. Mathur and colleagues⁶ identified WIT 35 minutes or longer as a risk factor for graft failure in DCD liver transplantation, but their series did not involve the systematic use of NRP. Although the follow-up was short, our recipient did not develop early ischemic cholangiopathy. This is consistent with the results of the Edinburgh group, which reported no ischemic-type biliary complications using NRP in 11 cases, but with a shorter WIT.⁷

In conclusion, DCD liver transplantation is feasible in Italy after a no-touch period of 20 minutes, in association with NRP. Our preliminary report suggests that NRP could help to push the limit of WIT much further without an increase in overall complications, although further research and data on long-term outcome are required.

ACKNOWLEDGMENTS

The authors thank Zanierato M (Anestesia e Rianimazione, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy) for the donor management.