Terlipressin in Septic Shock: Effects on Microcirculation

Overview

The present study was conducted as a prospective, randomized study to investigate the effects of vasopressin receptor agonists terlipressin and vasopressin on systemic hemodynamics and microcirculation in patients with catecholamine-dependent septic shock.

Full Title of Study: “Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: February 2010

Detailed Description

60 septic shock patients requiring norepinephrine to maintain mean arterial pressure between 65 and 75 mmHg despite adequate volume resuscitation will be enrolled in the study. After an initial hemodynamic resuscitation aimed at achieve a mean arterial pressure between 65 and 75 mmHg and normovolemia, patients will be randomly allocated to be treated with either a) intravenous administration of terlipressin 1 µg∙kg-1∙h-1 for 6 hrs, b) intravenous administration of arginine vasopressin 0.04 UI∙min-1 for 6 hrs, c) intravenous administration of terlipressin bolus dose of 0.5 mg (each n = 20). In all groups open label norepinephrine will be additionally administered to maintain a mean arterial pressure (MAP) between 65 and 75 mmHg, if necessary. Data from right heart catheterization and sublingual microvascular network will be obtained just before randomization (baseline) and then after 6 hours in the vasopressin, terlipressin infusion and terlipressin bolus groups. The sublingual microvascular network will be studied using the sidestream dark field (SDF)imaging. The device will be applied on the lateral side of the tongue, in an area approximately 2-4 cm from the tip of the tongue. Sequences of 10 secs from eight adjacent areas will be recorded on disk using a personal computer. These sequences will be later analyzed by an investigator blinded to the patient's diagnosis and therapy.

Interventions

  • Drug: continuous infusion of terlipressin
    • Intravenous continuous infusion of terlipressin 1 µg•kg-1•h-1 for 6 hrs
  • Drug: Arginine vasopressin
    • Intravenous continuous infusion of arginine vasopressin 0.04 UI•min-1 for 6 hrs
  • Drug: terlipressin bolus administration
    • intravenous terlipressin bolus administration at the dose of 0.5 mg

Arms, Groups and Cohorts

  • Experimental: continuous terlipressin
  • Experimental: vasopressin
  • Experimental: terlipressin bolus dose

Clinical Trial Outcome Measures

Primary Measures

  • Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)
    • Time Frame: over a period of 6 hrs from the time of randomization
  • Oxygen transport variables
    • Time Frame: over a period of 6 from the time of randomization

Secondary Measures

  • Acid-base homeostasis
    • Time Frame: over a period of 6 hrs from the time of randomization
  • Functional capillary density (mm/mm2) (FCD)
    • Time Frame: over a period of 6 hrs from the time of randomization
  • De Backer score
    • Time Frame: over a period of 6 hrs from the time of randomization
  • Perfused Vessel Density (PVD) (mm/mm2)
    • Time Frame: over a period of 6 hrs from the time of randomization
  • Proportion of Perfused vessels (%) (PPV)
    • Time Frame: over a period of 6 hrs from the time of randomization

Participating in This Clinical Trial

Inclusion Criteria

  • Clinical diagnosis of septic shock – Vasopressor support to maintain mean arterial pressure (MAP) between 65 and 75 mmHg despite adequate volume resuscitation (pulmonary artery occlusion pressure = 13-18 mmHg and central venous pressure = 8-12 mmHg) Exclusion Criteria:

  • Pregnancy – Age < 18 years – Present or suspected acute mesenteric ischemia – Vasospastic diathesis (e.g. Raynaud's syndrome or related diseases)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Roma La Sapienza
  • Provider of Information About this Clinical Study
    • Andrea Morelli, University of Rome “La Sapienza”
  • Overall Official(s)
    • Andrea Morelli, MD, Principal Investigator, University of Rome “La Sapienza”, Department of Anesthesiology and Intensive Care

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