Comparative Study of Terlipressin and Noradrenaline as Vasopressors in Patients With Acute-on-chronic Liver Failure and Septic Shock: A Randomized Controlled Trial

Abstract

Background

Sepsis is the most common acute insult in patients with acute-on-chronic liver failure (ACLF), and circulatory failure portends a poor prognosis in them.

Aim

This study aimed to compare terlipressin and noradrenaline as first-line vasopressors in patients with ACLF and septic shock.

Methods

This prospective, open-label, randomized controlled study was conducted from January 2021 to June 2022 at a tertiary care center. All patients presenting with ACLF as per the chronic liver failure consortium acute on chronic liver failure in cirrhosis study and septic shock were screened. Shock was defined as a mean arterial pressure (MAP) <65 mmHg/systolic blood pressure <90 mmHg. Patients with septic shock nonresponsive to crystalloids/colloids were randomized to receive terlipressin (group I) at 2.6 μg/kg/min and noradrenaline (group II) at 0.1 μg/kg/min. The primary outcome was an MAP >65 mmHg at 6 h. The secondary outcomes were 3-, 7-, 14-, and 28-day mortality, duration of hospital stay, cumulative dose of drug, and new events such as upper gastrointestinal bleed, acute kidney injury, jaundice, and hepatic encephalopathy within 28 days.

Results

A total of 70 patients were randomized to group I (n = 35) and group II (n = 35). According to per-protocol analysis, a higher number of patients achieved an MAP > 65 mmHg at 6 h in group II (n = 23/31, 74%) than in group I (5/34, 14%) (P < 0.001). The 3-and 7-day mortality was significantly higher in group I than in group II, with no difference at 14 and 28 days. The 28-day mortality was highest in ACLF grade-3 in both group II (22/25, 88%) and group I (15/20, 75%).

Conclusion

Terlipressin did not prove to be noninferior to norepinephrine, and therefore, norepinephrine should be the first-line vasopressor in ACLF patients with septic shock. The mortality rate was highest in ACLF grade-3 patients in both the groups, irrespective of the initial response to vasopressors. This indicates that holistic management of these patients is most important.