Terlipressin Administration in Patients Undergoing Major Liver Resection

Terlipressin Administration in Patients Undergoing Major Liver Resection: a Prospective Randomized Blinded Trial

Interim analysis revealed that no statistical difference will be identified after inclusion of the patient cohort as foreseen in the sample size calculation

This study investigates if the administration of terlipressin reduces complications after major liver surgery.

Background Surgery offers the only potential cure in many patients with primary or metastatic liver cancer. Extending the limits and improving safety of liver resection would allow more patients to benefit from surgery and to increase their survival. The prerequisite for successful and safe liver surgery is the optimal regeneration of the remaining hepatic tissue in order to fulfill the metabolic demands of the patient. Liver regeneration depends on a correct portal pressure and portal blood flow. In the preliminary results the investigators show an elevation of portal pressure post partial hepatectomy in mice. Pharmacologic reduction of such elevated portal pressure using terlipressin, a vasopressin agonist, was associated with improved liver regeneration. Objective Surgery offers the only potential cure in many patients with primary or metastatic liver cancer. Extending the limits and improving safety of liver resection would allow more patients to benefit from surgery and to increase their survival. Liver regeneration depends on a correct portal pressure and portal blood flow. Pharmacologic reduction of elevated portal pressure using terlipressin, a vasopressin agonist, is potentially associated with improved liver regeneration. Aim: To perform a prospective randomized trial comparing terlipressin versus placebo in patients undergoing major hepatic resection. Methods

Terlipressin given as intravenous injections of 1mg iv in 100ml of NaCl every 6 hours (total duration of drug administration 120 hours, cumulative dose is 20mg).

Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours).

Terlipressin given as intravenous injections of 1mg iv in 100ml of NaCl every 6 hours (total duration of drug administration 120 hours, cumulative dose is 20mg).

Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours).

Inclusion Criteria: Patients undergoing resection of 3 or more liver segments Minimum age of 18 Any gender Written informed consent Exclusion Criteria Preoperative renal failure (GFR < 50ml/min) Severe liver dysfunction (Child-Turcotte-Pugh grade C) Hyponatremia (<132mmol/l) Severe aortic regurgitation, severe mitral regurgitation, heart failure Symptomatic coronary heart disease Bradycardic arrhythmia (heart rate < 60/min) Peripheral artery occlusive disease (clinical stadium II-IV) Dilatative arteriopathy, history of subarachnoidal bleeding Decompensated arterial hypertension (Blood pressure >160/100mmHg despite intensive treatment) Present or suspected acute mesenteric ischemia Septic shock Pregnancy

Kohler A, Perrodin S, De Gottardi A, Candinas D, Beldi G. Effectiveness of terlipressin for prevention of complications after major liver resection - A randomized placebo-controlled trial. HPB (Oxford). 2020 Jun;22(6):884-891. doi: 10.1016/j.hpb.2019.10.011. Epub 2019 Oct 31.