Perioperative use of terlipressin in adult liver transplant

Alterations in the splanchnic circulation with a hyperdynamic circulation in patients are characteristic of cirrhosis. 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. Terlipressin also augments renal perfusion by increasing both effective blood volume and mean arterial pressure and may help prevent renal dysfunction after LT. 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. 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. The only plausible explanation could be the small number of patients enrolled in the study by Reddy et al. 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. We know that high portal flow impairs liver regeneration as seen in small-for-size syndrome, and thus adversely affects the postoperative recovery and reduction of portal flows by various methods whether medical or surgical helps in improvement of graft function. This study reiterates that terlipressin improves renal function. Because renal dysfunction can be due to multiple insults, including blood loss, prolonged surgery, renal ischemia, sepsis, and calcineurin inhibitors, use of terlipressin should be judicious and individualized. Improved renal perfusion and associated diuresis could also help in the control of ascites and drain output resulting in early mobilization and shorter hospital stay. The finding of higher blood lactate in the terlipressin group suggests that tissue hypoperfusion may result if restrictive fluid resuscitation is followed during the perioperative period. However, early good graft function and postoperative resuscitation may quickly reverse these changes as seen in this study. In this study, terlipressin was used for a short duration, suggesting that prolonged and overzealous use of terlipressin may be harmful. Because hepatic artery thrombosis is always a concern in patients with high and slow correction of lactate, this adverse effect of terlipressin should be borne in mind. The adverse effects of terlipressin have been demonstrated in the nontransplant setting; however, in most of these patients terlipressin is used for a prolonged duration depending on the indication. The significant cardiac adverse effect profile of terlipressin demonstrated in this study has not been highlighted in the previous studies. Hence intensive monitoring should be done in patients who are treated with terlipressin. The other adverse effects of terlipressin including diarrhea, abdominal cramping, hyponatremia, and digital gangrene are more commonly associated with high and bolus doses and prolonged usage of terlipressin and were not seen in this study. The use of terlipressin as a continuous infusion rather than bolus doses is another way of reducing the adverse effects as seen in this study and also in the nontransplant setting. This study suggests that routine use of terlipressin even if available is not recommended in the transplant Abbreviations: LT, liver transplantation.