Hemodynamic profile of terlipressin and octreotide in patients with cirrhosis and portal hypertension: a randomized, single-blind clinical trial

Abstract

Background & aims: Continuous infusion of terlipressin may result in a more sustained reduction in portal pressure with fewer adverse effects than administered as a bolus. This study aimed to compare the hepatic and cardiopulmonary hemodynamic effects and safety profiles of bolus vs. terlipressin continuous infusion.

Methods: This is a single-center, single-blinded, double-dummy, parallel-group, clinical trial in which 38 patients with cirrhosis and portal hypertension were randomized to receive the following: 1 mg bolus of terlipressin + continuous infusion of placebo (TERLBOL, n = 12), a bolus of placebo + continuous infusion of terlipressin (2 or 4 mg/day if <10% reduction in hepatic venous pressure gradient [HVPG] at 30 min of infusion) (TERLINF, n = 14), or a bolus of octreotide (50 μg) + continuous infusion of octreotide (50 μg/h) (OCTR, n = 12) as an additional control group. HVPG, cardiopulmonary pressures, and cardiac output were measured at baseline and after 30, 60, and 120 min.

Results: Sixty-eight percent of patients were male, with a median age of 59 years. There were no significant differences in baseline characteristics. In the TERLBOL group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.14). However, cardiopulmonary and mean arterial pressures significantly increased, whereas cardiac output and heart rate significantly decreased. In the TERLINF group, there were nonsignificant changes in cardiopulmonary hemodynamics or HVPG (NS) despite doubling the infusion dose after 30 min in 13/14 patients. In the OCTR group, there was a nonsignificant reduction in HVPG (at 120 min, -4.9%; p = 0.08), and pulmonary capillary pressure significantly decreased. All treatments were well tolerated, and no adverse events were observed.

Conclusions: There were nonsignificant reductions in HVPG with the three therapeutic strategies. Further investigations are warranted to determine the optimal dosing strategy for continuous infusion of terlipressin in patients with cirrhosis and portal hypertension.

Impact and implications: The results of our study do not show a significant reduction in portal pressure, at least in the first 2 h after the selected dose. Although the study was not performed in the setting of acute variceal bleeding and terlipressin was used as a standard therapy, these results do not support the treatment strategy of terlipressin infusion alone at the doses studied for the management of acute variceal bleeding, where a quick reduction in portal pressure is thought to play a major role controlling variceal bleeding. It is important to highlight that the continuously infused terlipressin regimen is better tolerated and appears to have a better cardiopulmonary safety profile. Other treatment strategies of continuous terlipressin infusion, such as initial bolus administration or higher infusion doses, should be evaluated to support its use in managing variceal bleeding.

Clinical trial identifier: EudraCT No. 2019-004328-39.

Keywords: Cirrhosis; Hepatic hemodynamics; Portal hypertension; terlipressin.

Graphical abstract

Fig. 1

CONSORT diagram of the total study cohort. HVPG, hepatic venous pressure gradient.

Fig. 2

HVPG changes during 2 h of treatment administration in the three groups. Treatment groups were analyzed in the longitudinal follow-up using generalized multilevel mixed effects models with an interaction p value of 0.85. HVPG, hepatic venous pressure gradient.