#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Abstract

Abstract Background and Aims Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis. Method A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4. Results A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06). Conclusion There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.