The effects of magnesium pretreatment on reperfusion injury during living donor liver transplantation

Abstract

Background: Ischemia reperfusion (IR) injury is a complex phenomenon that leads to organ dysfunction and causes primary liver failure following liver transplantation. We investigated whether an intravenous administration of magnesium before reperfusion can prevent or reduce IR injury.

Methods: Fifty-nine living donor liver transplant recipients were randomly assigned to an MG group (n = 31) or an NS group (n = 28). Each group was also divided in two groups based on the preoperative magnesium levels (normal: ≥ 0.70 mmol/L, low: < 0.70 mmol/L). The MG groups received 25 mg/kg of MgSO(4) mixed in 100 ml normal saline intravenously before reperfusion and the NS groups received an equal volume of normal saline. The levels of lactate, pH, arterial oxygen tension, and base excess were measured to assess reperfusion injury at five specific times, which were 10 min after the beginning of anhepatic phase, and 10, 30, 60 and 120 min after reperfusion. To evaluate postoperative organ function, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and creatinine levels were measured at preoperative day 1, postoperative day 1 and 5.

Results: The blood lactate levels were significantly lower at 10, 30, 60 and 120 min after reperfusion in the MG groups compared to the NS groups. In addition, significantly higher blood lactate levels were observed in the NS group with preoperative hypomagnesemia than in MG groups.

Conclusions: Magnesium administration before reperfusion of liver transplantation significantly reduces blood lactate levels. These findings suggest that magnesium treatment may have protective effects on IR injury during living donor liver transplantation.

Keywords: Ischemia reperfusion injury; Lactate; Living donor liver transplantation; Magnesium.

Fig. 1

Changes in magnesium concentration during living donor liver transplantation. The magnesium concentrations significantly increased after magnesium administration in Normal-MG and Low-MG group. Preop: preoperative 1 day, Anhepatic + 10 min: 10 minute after the beginning of anhepatic phase, Reperfusion + 10 min: 10 minute after reperfusion, POD 1: postoperative 1 day. The normal range of serum magnesium concentration is 0.70 to 1.10 mmol/L. Normal-NS: NS group with preoperative magnesium levels ≥ 0.70 mmol/L, Normal-MG: magnesium-treated group with preoperative magnesium levels ≥ 0.70 mmol/L, Low-NS: NS group with preoperative magnesium levels < 0.70 mmol/L, Low-MG: magnesium-treated group with preoperative magnesium levels < 0.70 mmol/L. Data are the mean ± SD. ^*P < 0.05 compared with Normal-NS group, ^†P < 0.05 compared with Low-NS group. ^‡P < 0.05 compared with Preop by Bonferroni correction.

Fig. 2

Changes in blood lactate levels before and after reperfusion in living donor liver transplantation. Significantly higher blood lactate levels were observed in the Low-NS group compared to magnesium-treated groups after reperfusion. Normal-NS: NS group with preoperative magnesium levels ≥ 0.70 mmol/L, Normal-MG: magnesium-treated group with preoperative magnesium levels ≥ 0.70 mmol/L, Low-NS: NS group with preoperative magnesium levels < 0.70 mmol/L, Low-MG: magnesium-treated group with preoperative magnesium levels < 0.70 mmol/L. Data are the mean ± SD. ^*P < 0.05 compared with Normal-MG group, ^†P < 0.05 compared with Low-MG group.

Fig. 3

Changes of physiological parameters before and after reperfusion in living donor liver transplantation. (A) pH, (B) PaO₂, (C) MAP, (D) Base excess. After reperfusion, pH values were significantly decreased compared to anhepatic + 10 min. No significant difference was observed between the groups. Data are the mean ± SD. Anhepatic + 10 min: 10 min after the beginning of the anhepatic phase, Reperfusion + 10, 30, 60 and 120 min: 10, 30, 60 and 120 min after reperfusion, MAP: mean arterial pressure. Normal-NS: NS group with preoperative magnesium levels ≥ 0.70 mmol/L, Normal-MG: magnesium-treated group with preoperative magnesium levels ≥ 0.70 mmol/L, Low-NS: NS group with preoperative magnesium levels < 0.70 mmol/L, Low-MG: magnesium-treated group with preoperative magnesium levels < 0.70 mmol/L. ^*P < 0.05 compared with Anhepatic + 10 min by Bonferroni correction.

Fig. 4

Changes of serum AST, ALT, total bilirubin and creatinine levels before and after living donor liver transplantation. All parameters were observed to significantly increase at POD 1 and decrease at POD 5, but there was no difference between the groups. Normal-NS: NS group with preoperative magnesium levels ≥ 0.70 mmol/L, Normal-MG: magnesium-treated group with preoperative magnesium levels ≥ 0.70 mmol/L, Low-NS: NS group with preoperative magnesium levels < 0.70 mmol/L, Low-MG: magnesium-treated group with preoperative magnesium levels < 0.70 mmol/L. AST: aspartate aminotransferase, ALT: alanine aminotransferase. Preop: preoperative value (one day before surgery), POD 1: postoperative 1 day, POD 5: postoperative 5 day. ^*P < 0.05 when compared with Preop by Bonferroni correction.