Double‐blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation

Abstract

Perioperative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intraoperative portal pressures and improve renal function. Its role and safety profile have never been evaluated in a double-blind randomized controlled trial (RCT). The aim was to evaluate the hemodynamic effects, clinical benefits, and safety of perioperative Tp infusion in adult LDLT. This was a single-center double-blind RCT. Consenting adults with chronic liver disease and low risk of posttransplant renal dysfunction undergoing their first LDLT were randomized. The study group (terlipressin group [TpG]) received an initial bolus of Tp during surgery followed by a Tp infusion for 72 hours in the postoperative period. The placebo group (PbG) received a saline infusion. The primary endpoint was portal pressure after arterial reperfusion. Multiple intraoperative and postoperative variables served as secondary endpoints. A total of 41 patients were enrolled in the trial (TpG, 21; PbG, 20). There were no significant differences in intraoperative portal pressures, blood loss, fluid requirement, vasopressor requirement, or urine output. Peak intraoperative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in postoperative liver function tests. Incidence of acute kidney injury as assessed by Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria was lower in the Tp group (27% versus 60%; P = 0.04). The TpG had less postoperative ascites, a lower need for percutaneous interventions, and a shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in the TpG. In conclusion, this study has not demonstrated a reduction in postreperfusion portal pressure with Tp. However, Tp infusion reduced postoperative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intraoperative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high-volume ascites, and it needs close monitoring during drug infusion. Liver Transplantation 23 1007-1014 2017 AASLD.

Effectiveness of terlipressin for prevention of complications after major liver resection – A randomized placebo-controlled trial

“…10 Recent clinical data and experiments in mice with non-cirrhotic livers have demonstrated a positive effect of terlipressin on portal hemodynamics and also on regeneration after living donor liver transplantation and extended liver resection. [11][12][13] Thereby we hypothesized that terlipressin could be used as an adjuvant treatment in liver surgery to reduce postoperative complications that were used as the primary end point.…”

Prevalence and short-term outcome of hepatorenal syndrome: A 9-year experience in a high-complexity hospital in Colombia

“…The prognosis with any drug therapy remains poor and liver transplant is the definitive treatment [22]. Some benefits are described in the use of terlipressin in pre-transplant and post-transplant period, decreasing morbidity and improving patient outcomes [23].…”

Perioperative use of terlipressin in adult liver transplant

“…Others have demonstrated a reduction in portal pressure in the perioperative period of liver transplant previously, although a recent meta-analysis did not demonstrate significant hemodynamic changes, which reflects the heterogeneity of studies conducted so far. (3,6,7) The only plausible explanation could be the small number of patients enrolled in the study by Reddy et al (5) and the difference in reduction of portal pressures not reaching statistical significance, though there was a trend toward greater reduction in the terlipressin group. Another explanation could be a spontaneous reduction of the portal blood flow due to good graft function.…”

“…(1) Terlipressin may have a role in reducing portal hypertension in liver transplantation (LT), although it is not yet licensed in the United States. Because terlipressin is a selectively V1 receptor agonist and causes splanchnic arteriolar vasoconstriction and a consequent shift of blood into the systemic circulation, it might aid in reducing venous congestion, reduction in blood loss, and maintaining arterial blood pressure perioperatively.(2) Terlipressin also augments renal perfusion by increasing both effective blood volume and mean arterial pressure and may help prevent renal dysfunction after LT. (3,4) In this issue of Liver Transplantation, the doubleblinded study by Reddy et al (5) demonstrates a beneficial perioperative role of terlipressin in LT patients. However, the intriguing finding of the study is no apparent reduction of portal pressure.…”

“…(2) Terlipressin also augments renal perfusion by increasing both effective blood volume and mean arterial pressure and may help prevent renal dysfunction after LT. (3,4) In this issue of Liver Transplantation, the doubleblinded study by Reddy et al (5) demonstrates a beneficial perioperative role of terlipressin in LT patients. However, the intriguing finding of the study is no apparent reduction of portal pressure.…”