Volume 37, Issue 4 pp. 552-561
LIVER FAILURE, CIRRHOSIS AND ITS COMPLICATIONS

A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock

Ashok Choudhury

Ashok Choudhury

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Chandan K. Kedarisetty

Chandan K. Kedarisetty

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Chitranshu Vashishtha

Chitranshu Vashishtha

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Deepak Saini

Deepak Saini

Department of Critical care, Institute of Liver and Biliary Sciences, New Delhi, India

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Sachin Kumar

Sachin Kumar

Department of Pulmonology, Institute of Liver and Biliary Sciences, New Delhi, India

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Rakhi Maiwall

Rakhi Maiwall

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Manoj K. Sharma

Manoj K. Sharma

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Ajeet S. Bhadoria

Ajeet S. Bhadoria

Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India

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Guresh Kumar

Guresh Kumar

Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India

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Yogendra K. Joshi

Yogendra K. Joshi

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Shiv K. Sarin

Corresponding Author

Shiv K. Sarin

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

Correspondence

Dr. Shiv K. Sarin, MD, DM, Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), New Delhi 110 070, India.

Email: [email protected]

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First published: 16 September 2016
Citations: 70
Handling Editor: Stanislas Pol
Clinicaltrials.gov identifier: NCT01836224.

Abstract

Background & Aims

The choice of vasopressor for treating cirrhosis with septic shock is unclear. While noradrenaline in general is the preferred vasopressor, terlipressin improves microcirculation in addition to vasopressor action in non-cirrhotics. We compared the efficacy and safety of noradrenaline and terlipressin in cirrhotics with septic shock.

Patients and Methods

Cirrhotics with septic shock underwent open label randomization to receive either terlipressin (n=42) or noradrenaline (n=42) infusion at a titrated dose. The primary outcome was mean arterial pressure (MAP) >65 mm Hg at 48 h.

Results

Baseline characteristics were comparable between the terlipressin and noradrenaline groups.SBP and pneumonia were major sources of sepsis. A higher proportion of patients on terlipressin were able to achieve MAP >65 mm of Hg (92.9% vs 69.1% P=.005) at 48 h. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin (33.3% vs 11.9%, P<.05). Terlipressin compared to noradrenaline prevented variceal bleed (0% vs 9.5%, P=.01) and improved survival at 48 h (95.2% vs 71.4%, P=.003). Percentage lactate clearance (LC) is an independent predictor of survival [P=.0001, HR=3.9 (95% CI: 1.85-8.22)] after achieving the target MAP.Therapy related adverse effect were comparable in both the arms (40.5% vs 21.4%, P=.06), mostly minor (GradeII-88%) and reversible.

Conclusions

Terlipressin is as effective as noradrenaline as a vasopressor in cirrhotics with septic shock and can serve as a useful drug. Terlipressin additionally provides early survival benefit and reduces the risk of variceal bleed. Lactate clearance is a better predictor of outcome even after achieving target MAP, suggesting the role of microcirculation in septic shock.

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