Terlipressin in Septic Shock: Effects on Microcirculation

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Vasopressin Receptor Agonists in Septic Shock: Effects on Microcirculation

Conditions
-----------------
Septic Shock, Sepsis

Intervention / Treatment
-----------------
* Drug: continuous infusion of terlipressin
* Drug: Arginine vasopressin
* Drug: terlipressin bolus administration


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: continuous terlipressin<br> | Drug: continuous infusion of terlipressin<br>* Intravenous continuous infusion of terlipressin 1 µg•kg-1•h-1 for 6 hrs<br>|
| Experimental: vasopressin<br> | Drug: Arginine vasopressin<br>* Intravenous continuous infusion of arginine vasopressin 0.04 UI•min-1 for 6 hrs<br>|
| Experimental: terlipressin bolus dose<br> | Drug: terlipressin bolus administration<br>* intravenous terlipressin bolus administration at the dose of 0.5 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI) |  | over a period of 6 hrs from the time of randomization | 
| Oxygen transport variables |  | over a period of 6 from the time of randomization | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vasopressin, terlipressin, sepsis, septic shock, norepinephrine