Double-blind Randomized controlled trial of the peri-operative use of terlipressin in adult living donor liver transplantation.

Cirrhosis is associated with portal hypertension. Shift of blood to the splanchnic circulation with relative decrease of the systemic circulation volume is also well described. This manifests as increased bleeding secondary to portal hypertension during liver transplantation. Peri-operative renal dysfunction is also well described. Living donor liver transplantation involves transplanting a graft liver, which is half the normal liver size into the recipient. This exposes the graft to high portal blood flow termed ‘portal hyperperfusion’. While it resolves spontaneously in mild cases, it has the potential to cause prolonged graft dysfunction when the graft recipient weight ratio (GRWR) is less than 0.8. This is termed ‘small for size syndrome’.

Terlipressin is a vasopressin analogue, which causes splanchnic vasoconstriction leading to a shift of blood from portal to systemic circulation. It is routinely used in management of variceal bleeding and hepato-renal syndrome in cirrhotic patients. Terlipressin can potentially improve outcome in LDLT by decreasing intra-operative haemorrhage, improving renal function and decreasing portal hyperperfusion. It has been reported to improve outcomes in LDLT in a few recent studies. However this area needs further investigation.

The present study is planned as a double blind, randomised controlled trial comparing the use of terlipressin during the peri-transplant period with a placebo group. This study will enroll adults patients undergoing LDLT in our unit with GRWR lesser than 1.2. Subjects will be randomised to terlipressin group or placebo group. Terlipressin group will receive an initial bolus of terlipressin at start of transplant operation followed by continuous infusion for 72 hours post-operatively. Placebo group will receive saline infusion at the same rate loaded in similar looking syringes. The patient and the treating clinicians will be unaware of each patient’s allocation. The primary end-point is a drop in portal pressure after implantation. Secondary end-points of the trial include intra-operative haemo-dynamic parameters, intra-operative blood loss, transfusion requirements, post-operative liver function tests, renal function and morbidity. In addition, histological markers of tissue injury will be compared between the two groups. If significant improvement in post-transplant outcomes can be achieved by the use of peri-operative terlipressin, the latter can become the standard of care for all adult LDLT.