Avoiding initial hypothermia does not improve liver graft quality in a porcine donation after circulatory death (DCD) model of normothermic perfusion

Abstract

Background Normothermic machine perfusion (NMP) of liver grafts donated after circulatory death (DCD) has shown promise in large animal and clinical trials. Following procurement, initial flush with a cold preservation solution is the standard of care. There is concern that initial cooling followed by warming may exacerbate liver injury, and the optimal initial flush temperature has yet to be identified. We hypothesize that avoidance of the initial cold flush will yield better quality liver grafts. Methods Twenty-four anaesthetized pigs were withdrawn from mechanical ventilation and allowed to arrest. After 60-minutes of warm ischemia to simulate a DCD procurement, livers were flushed with histidine-tryptophan-ketoglutarate (HTK) at 4°C, 25°C or 35°C (n = 4 per group). For comparison, an adenosine-lidocaine crystalloid solution (AD), shown to have benefit at warm temperatures in heart perfusions, was also used (n = 4 per group). During 12-hours of NMP, adenosine triphosphate (ATP), lactate, transaminase levels, and histological injury were determined. Bile production and hemodynamics were monitored continuously. Results ATP levels recovered substantially following 1-hour of NMP reaching pre-ischemic levels by the end of NMP with no difference between groups. There was no difference in peak aspartate aminotransferase (AST) or in lactate dehydrogenase (LDH). Portal vein resistance was lowest in the 4°C group reaching significance after 2 hours (0.13 CI -0.01,0.277, p = 0.025). Lactate levels recovered promptly with no difference between groups. Comparison to AD groups showed no statistical difference in the abovementioned parameters. On electron microscopy the HTK4°C group had the least edema with mean cell thickness of 2.92μm (p = 0.41) while also having the least sinusoidal dilatation with a mean diameter of 5.36μm (p = 0.04). For AD, the 25°C group had the lowest mean cell thickness at 3.14μm (p = 0.09). Conclusions Avoidance of the initial cold flush failed to demonstrate added benefit over standard 4°C HTK in this DCD model of liver perfusion.

En bloc procurement of porcine abdominal multiple organ block for ex situ normothermic machine perfusion: a technique for avoiding initial cold preservation

“…In addition, if cold preservation is carried out, the AMOB will undergo a process of cooling and rewarming in a short time, and whether rapid cooling and rewarming affect the NMP results is another problem. However, one study demonstrated that avoiding cold preservation does not improve liver quality in a porcine DCD model of NMP (26). Actually, eliminating cold preservation also resulted in some slight negative effects; most visible was that the lactic acid level was slightly higher in the beginning.…”

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

“…When comparing NMP to SNMP and SCS, NMP was most efficient in terms of recovery of DCD livers (67). Avoiding initial hypothermia did not improve liver graft quality in a porcine DCD model of NMP (73). Recently, the first randomized controlled trial showed a 50% reduction in liver graft injury, despite a 50% decrease in the number of discarded organs and a 54% increased mean preservation time after a period of NMP compared to SCS (∼36% of grafts were DCD).…”

Long-term normothermic machine preservation of human livers: what is needed to succeed?

“…Markedly different doses are being used. Most often 500 mg methylprednisolone per perfusion per 24 h or 10 mg/L hydrocortisone are administered (11,14,15,65). However, whether this is effective has not yet been clarified, nor have the possible harmful consequences.…”

“…A decrease in perfusate glucose level appears to be a good sign of liver function, as hepatocytes take up glucose with subsequent conversion to glycogen (58). Some groups administer boluses or a continuous glucose infusion to keep the perfusate glucose level in a specific range (19,65,79). Others administer total parenteral nutrition meant for humans instead of glucose alone when the perfusate glucose drops below a particular value (8,12,88).…”

“…One group supplied glucagon when glucose dropped below a certain threshold (15). On the other hand, insulin is almost always supplied during perfusion even when the high perfusate glucose levels in the first hours of perfusion appear to be resistant to insulin (8,10,12,19,56,65,87).…”