Nafamostat Mesilate Attenuates Postreperfusion Syndrome during Liver Transplantation

Abstract

Postreperfusion syndrome (PRS), an acute decrease in blood pressure after reperfusion of the liver graft, occurs frequently during liver transplantation surgery. We supposed that the activation of the kallikrein-kinin system leading to extensive systemic vasodilatation was a possible cause. The effect of pretreatment with nafamostat mesilate (NM), a broad spectrum serine protease inhibitor, on the occurrence of PRS was evaluated. Sixty-two adult liver recipients were randomized to receive an intravenous bolus of either 0.02 mg/kg of NM (NM group, n = 31) or an equal volume of normal saline (control group, n = 31) just before reperfusion of the liver graft. Occurrence of PRS and intraoperative use of vasoactive drugs were compared between the two groups. Postoperative recovery was also compared. PRS was significantly less frequent (48% vs. 81%, p = 0.016) requiring less vasopressors in the NM group compared to the control group. The NM group also showed faster recovery of the mean arterial pressure. Perioperative laboratory values were similar between the two groups. Pretreatment with 0.02 mg/kg of NM immediately before reperfusion decreases the frequency of PRS and vasopressor requirements during the reperfusion period in liver transplantation.

Recent Advances on Plasmin Inhibitors for the Treatment of Fibrinolysis‐Related Disorders

“…Reports suggest that prophylactic intravenous nafamostat mesilate reduces the frequency of postendoscopic retrograde cholangiopancreatography pancreatitis . Nafamostat is also useful as an anticoagulant during continuous venous hemodialysis and it attenuates postreperfusion syndrome during liver transplantation . Likewise, gabexate appears to be pharmacologically useful in pancreatitis, liver transplantation, and hemodialysis anticoagulation .…”

“…Moreover, although not fully understood, TXA has been implicated in the treatment of melasma, prevention of UV-induced pigmentation, and the recovery of skin barrier. 270,271 Finally, nafamostat and gabexate have been found useful for complex pathologies such as DIC, 7,137,148 pancreatitis, [138][139][140][141][142][143][144] and liver diseases. 272…”

A comparison of intra‐operative blood loss and acid–base balance between vasopressor and inotrope strategy during living donor liver transplantation: a randomised, controlled study

“…In addition, we did not observe a difference in the incidence of post‐reperfusion syndrome, which might have been expected with a reduction in portal hypertension and splanchnic hyperaemia associated with a vasopressor strategy. Although factors causing hypotension after reperfusion of the liver graft are yet to be defined, the potent vasodilatory action of bradykinin, a product of the kallikrein–kinin system, is considered to be the most likely cause of post‐reperfusion syndrome [29].…”

Performance measurement of intraoperative systolic arterial pressure to predict in-hospital mortality in adult liver transplantation

“…However, acute changes caused by massive bleeding, volume resuscitation, and administration of potent vasopressors are often hidden in that interval. It has been pointed out that retrospective studies with low resolution data can distort the incidence of PRS, where patients frequently recover from severe hypotension within 5 minutes following appropriate treatment 17 . However, single hypotensive event with immediate recovery is less likely to be associated with adverse outcomes.…”