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

Liver Int. 2017 Apr;37(4):552-561. doi: 10.1111/liv.13252. Epub 2016 Oct 20.

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.

Trial registration: ClinicalTrials.gov NCT01836224.

Keywords: cirrhosis; septic shock; terlipressin; vasopressor.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Female
  • Hemodynamics
  • Humans
  • India
  • Kaplan-Meier Estimate
  • Lactic Acid / blood
  • Liver Cirrhosis / complications*
  • Logistic Models
  • Lypressin / administration & dosage
  • Lypressin / adverse effects
  • Lypressin / analogs & derivatives*
  • Male
  • Microcirculation
  • Middle Aged
  • Norepinephrine / administration & dosage*
  • Norepinephrine / adverse effects
  • Shock, Septic / drug therapy*
  • Terlipressin
  • Vasoconstrictor Agents / administration & dosage*

Substances

  • Vasoconstrictor Agents
  • Lactic Acid
  • Lypressin
  • Terlipressin
  • Norepinephrine

Associated data

  • ClinicalTrials.gov/NCT01836224