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Low-dose continuous terlipressin infusion is effective and safer than intravenous bolus injections in reducing portal pressure and control of acute variceal bleeding

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Abstract

Background and aims

Continuous infusion of terlipressin is better tolerated, and equally effective at lower doses than intravenous boluses in type 1 hepatorenal syndrome. This approach in cirrhosis patients with acute esophageal variceal bleed was investigated by comparing the efficacy and adverse events of continuous versus bolus administration of terlipressin.

Methods

One hundred ten consecutive cirrhosis patients with acute esophageal variceal bleed (AEVB) were randomized to receive either terlipressin as bolus (BOL, n = 55), 2 mg every 4 h, or, continuous infusion (CONI, n = 55), 4 mg/24 h for 5 days. Hepatic venous pressure gradient (HVPG) was measured at baseline, 12 and 24 h and response to terlipressin was defined as > 10% decline from baseline.

Results

Baseline demographics, model for end-stage liver disease (MELD) and HVPG were comparable between groups. The primary objective of HVPG response at 24 h was achieved in significantly more patients in CONI than BOL group {47/55(85.4%) vs. 32/55(58.2%), p = 0.002}. Early HVPG response at 12 h was also higher in CONI group (71.5 vs. 49.1%, p < 0.01). Median dose of terlipressin was significantly lower {4.25 ± 1.26 mg vs. 7.42 ± 1.42 mg/24 h, p < 0.001)} and adverse events were fewer {20/55(36.3%) vs. 31/55(56.4%), p = 0.03} in the CONI than BOL group. Significantly higher incidence of very early rebleed was noted in BOL group {8/55 (14.5%) vs. 1/55, (1.8%), p = 0.03}. Baseline HVPG (OR 1.90, 95% CI = 1.25–2.89, p = 0.002) and MELD (OR 1.18, 95% CI = 0.99–1.41, p = 0.05) were predictors of rebleed.

Conclusion

“HVPG-tailored” continuous terlipressin infusion is more effective than bolus administration in reducing HVPG at a lower dose with fewer adverse events in cirrhotic patients.

Clinical trial identifier

NCT02695862.

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Abbreviations

HVPG:

Hepatic venous pressure gradient

CTP:

Child–Turcotte–Pugh

MELD:

Model for end-stage liver disease

BOL:

Bolus

CONI:

Continuous infusion

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Author notes

  1. Vinod Arora and Shakti Prasad Choudhary are joint first authors.

Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, India

    Vinod Arora, Shakti Prasad Choudhary, Rakhi Maiwall, Rajan Vijayaraghavan, Ankur Jindal & Shiv Kumar Sarin

  2. Department of Clinical Research and Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India

    Guresh Kumar

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  1. Vinod Arora
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Contributions

Protocol: SPC, VA, SKS, RM, and AJ. Study design: SPC, VA, SKS, RM, and AJ. Patient recruitment: VA, SPC, and VR. Data acquisition: VA, SKC, and VR. Data analysis: GK. Manuscript drafting: VA, SPC, and SKS. Manuscript revision and approval: SKS, RM, VA, AJ, GK, and SPC.

Corresponding author

Correspondence to Shiv Kumar Sarin.

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Conflict of interest

Vinod Arora, Shakti Prasad Choudhary, Rakhi Maiwall, Rajan Vijayaraghavan, Ankur Jindal, Guresh Kumar and Shiv Kumar Sarin declare that they have no conflict of interest.

Ethical approval

The study protocol conformed to the Declaration of Helsinki and was approved by the Institutional Ethics Committee. The study followed the CONSORT guidelines and was registered at the ClinicalTrials.gov (identifier: NCT02695862).

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A written informed consent was taken at enrollment.

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Supplementary file1 KM curve showing 28 day survival (TIF 32 KB)

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Arora, V., Choudhary, S.P., Maiwall, R. et al. Low-dose continuous terlipressin infusion is effective and safer than intravenous bolus injections in reducing portal pressure and control of acute variceal bleeding. Hepatol Int 17, 131–138 (2023). https://doi.org/10.1007/s12072-022-10416-6

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  • DOI: https://doi.org/10.1007/s12072-022-10416-6

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