Clinical trial NCT00800306: Effects of Levosimendan on Microcirculation in Septic Shock
Official title: Levosimendan and Inhaled Nitric Oxide for Resuscitating the Microcirculation in Septic Shock. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Septic Shock
Keywords: sepsis
septic shock
microcirculation
levosimendan
dobutamine
inotropes
inhaled nitric oxide
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2008-12-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present study was conducted as a prospective, randomized, controlled study to:

* investigate the effects of a combination of levosimendan and inhaled nitric oxide on systemic hemodynamics and microcirculation in patients with catecholamine-dependent septic shock;
* test the hypothesis that levosimendan plus inhaled nitric oxide may be effective in restoring microvascular function in septic shock.

Detailed description: 40 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 a mixed venous oxygen saturation (SvO2) ≥ 65%, patients will be randomly allocated to be treated with either a) intravenous administration of levosimendan 0.2 µg∙kg-1∙min-1 for 24 hrs, b)intravenous administration of dobutamine 5 µg∙kg-1∙min-1 for 36 hrs(control; each n = 20). At the end of the first 24 hrs of the study period, both groups will receive inhaled nitric oxide at the concentration of 35 ppm for further 12 hrs. In all patients norepinephrine was titrated to maintain mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization and sublingual microvascular network will be obtained just before randomization (baseline) and then after 24 and 36 hours.

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.

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
* Ventricular outflow tract obstruction
* Mitral valve systolic anterior motion

Primary outcomes:
measure: Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)
timeFrame: over a period of 36 hrs from the time of randomization
Secondary outcomes:
measure: Acid-base homeostasis
timeFrame: over a period of 36 hrs from the time of randomization
measure: Oxygen transport variables
timeFrame: over a period of 36 hrs from the time of randomization
measure: Functional capillary density (mm/mm2) (FCD)
timeFrame: over a period of 36 hrs from the time of randomization
measure: De Backer score
timeFrame: over a period of 36 hrs from the time of randomization
measure: Perfused Vessel Density (PVD) (mm/mm2)
timeFrame: over a period of 36 hrs from the time of randomization
measure: Proportion of Perfused vessels (%) (PPV)
timeFrame: over a period of 36 hrs from the time of randomization
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Departement of Anesthesiology and Intensive Care of the University of Rome "La Sapienza" Viale del Policlinico 155
Study officials:
affiliation: University of Rome "La Sapienza", Department of Anesthesiology and Intensive Care
name: Andrea Morelli, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morelli A, Donati A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Landoni G, Pelaia P, Pietropaoli P, Van Aken H, Teboul JL, Ince C, Westphal M. Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care. 2010;14(6):R232. doi: 10.1186/cc9387. Epub 2010 Dec 23.