Terlipressin in Septic Shock: Effects on Microcirculation

University of Roma La Sapienza

Status and phase: Completed; Phase 3; Phase 2

Conditions: Septic Shock; Sepsis

Treatments: Drug: Arginine vasopressin; Drug: terlipressin bolus administration; Drug: continuous infusion of terlipressin

Study type: Interventional

Funder types: Other

Identifiers

NCT00995839

1065

Details and patient eligibility

About

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 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 3 patient groups

continuous terlipressin

Experimental group

Treatment:

Drug: continuous infusion of terlipressin

vasopressin

Experimental group

Treatment:

Drug: Arginine vasopressin

terlipressin bolus dose

Experimental group

Treatment:

Drug: terlipressin bolus administration