Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Abstract

Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE-preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 ± 2 and 34 ± 6 mmol potassium and took up 25 ± 9 and 24 ± 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE-preserved livers took up a mean of 19 ± 3 mmol potassium, while controls released 8 ± 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE-preserved livers while levels increased after reperfusion of SCS-preserved liver, delta potassium levels were -0.77 ± 0.20 vs. +0.64 ± 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS-preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient.

Keywords: donors and donation; liver transplantation/hepatology; organ perfusion and preservation; translational research/science.

Figure 1

Mean potassium levels in perfusion fluid during DHOPE and NMP of preclinical livers. At baseline (time point zero), samples of the perfusion fluid were taken before the liver was connected to the perfusion device (Liver Assist). Potassium levels increased significantly during the first 30 minutes of DHOPE (*P = .03) and stabilized thereafter. During ex situ NMP of DHOPE‐preserved livers, potassium levels decreased significantly during the first 30 minutes (**P = .001) and stabilized thereafter. In contrast, during ex situ NMP of control livers, potassium levels increased significantly during the first 30 minutes (***P = .04) and stabilized thereafter. Note the different Y‐scales for DHOPE and NMP

Figure 2

Mean sodium levels in perfusion fluid during DHOPE and NMP of preclinical livers. At baseline (time point zero), samples of the perfusion fluid were taken before the liver was connected to the perfusion device (Liver Assist). Sodium levels remained stable during the first 30 minutes of DHOPE, but levels significantly decreased thereafter (*P = .06). During ex situ NMP of DHOPE‐preserved livers, no changes in sodium perfusate levels were observed in the first 30 minutes of NMP and levels remained to be stable thereafter. In contrast, during ex situ NMP of control livers, sodium levels significantly decreased during the first 30 minutes (**P = .02) and stabilized thereafter. Note the different Y‐scales for DHOPE and NMP

Figure 3

Mean potassium levels in perfusion fluid during DHOPE and in recipient blood samples during subsequent orthotopic liver transplantation (OLT). At baseline (time point zero), samples of the perfusion fluid were taken before the liver was connected to the perfusion device (Liver Assist). Potassium levels in the perfusion fluid increased significantly during the first 30 minutes of DHOPE (*P < .001), and stabilized thereafter. During OLT of DHOPE‐preserved livers, blood potassium levels decreased significantly after reperfusion (**P = .003). Moreover, at the time of graft reperfusion, blood potassium levels were significantly lower in DHOPE patients when compared to potassium levels at that time point in control patients (***P = .03). Note the different Y‐scales for DHOPE and NMP

Figure 4

Mean sodium levels in perfusion fluid during DHOPE and in recipient blood samples during subsequent orthotopic liver transplantation (OLT). At baseline (time point zero), samples of the perfusion fluid were taken before the liver was connected to the perfusion device (Liver Assist). Sodium levels in the perfusion fluid slightly decreased, during the first 30 minutes of DHOPE as well as during the remainder of DHOPE, yet not significantly. During OLT of DHOPE‐preserved livers, blood sodium levels increased significantly after reperfusion (*P = .04). During OLT of control livers, blood sodium levels slightly decreased after reperfusion, yet not significantly. Note the different Y‐scales for DHOPE and NMP

Figure 5

Changes in intraoperative hemodynamics upon reperfusion. No significant changes in mean arterial pressure (MAP) were noted after reperfusion of both DHOPE and control livers (A) while noradrenaline requirements increased in both groups (B). Increased noradrenaline dose upon reperfusion significantly correlated with increased potassium levels (C) and decreased sodium levels (D); P = .01 and P = 0.008, respectively

Figure 6

Overview of potassium and sodium shifts during organ preservation and subsequent warm reperfusion. This cartoon summarizes cation shifts during hypothermic machine perfusion in both preclinical and clinical livers, and during subsequent warm reperfusion in the preclinical study. During static cold storage (SCS), donor livers were preserved in a high potassium and low sodium preservation solution, containing 125 mmol/L potassium and 29 mmol/L sodium. During warm reperfusion of SCS‐preserved livers, a mean total hepatic potassium release of 8 mmol and a mean total hepatic sodium uptake of 23 mmol was observed. During hypothermic oxygenated machine perfusion, a mean total hepatic potassium release of 17 mmol in the preclinical and 34 mmol in the clinical study was noted. Simultaneously, a total hepatic sodium uptake of 25 mmol was noted during hypothermic machine perfusion in the preclinical study and of 24 mmol in the clinical study. Opposite cation shifts were observed during subsequent warm reperfusion of liver grafts. During reperfusion of DHOPE‐preserved livers, a total hepatic potassium uptake of 19 mmol and a total hepatic sodium release of 7 mmol was noted, whereas reperfusion of a SCS‐preserved livers was associated with a total hepatic release of 8 mmol potassium and a total hepatic uptake of 23 mmol of sodium. These differences in cation shifts explains the risk of a postreperfusion systemic hyperkalemia in recipients of a conventional SCS‐preserved liver and a decrease in blood potassium levels in recipients of a DHOPE‐preserved liver. UW, University of Wisconsin; SCS solution, static cold storage solution; MP solution, machine perfusion solution