Effects of Dobutamine on Microcirculation, Regional and Peripheral Perfusion in Septic Shock Patients

Study Overview
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Brief Summary
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The investigators hypothesize that dobutamine is able to revert negative redistribution of flow by inducing a selective vasodilatory effect on hypoperfused territories, particularly at the sublingual and gastric mucosa, and at the peripheral tissues. The investigators designed a randomized, cross-over, placebo-controlled study looking at the acute physiologic effects of 5 mcg/kg/min fixed-dose of dobutamine on cardiac function, microcirculation, gastric mucosal, hepatosplanchnic, and peripheral perfusion in septic shock patients.

Detailed Description
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The investigators hypothesize that dobutamine is able to revert negative redistribution of flow by inducing a selective vasodilatory effect on hypoperfused territories, particularly at the sublingual and gastric mucosa, and at the peripheral tissues. Therefore, dobutamine improves microcirculatory alterations and regional perfusion in septic shock, independent of its effects on cardiac output. The relevance of this concept is that it would support a more rational use of dobutamine in septic shock patients, not only as an inotrope to increase cardiac output, but more important, as a selective vasodilator aimed at restoring perfusion. Therefore, the investigators designed a randomized, cross-over, placebo-controlled study looking at the acute physiologic effects of 5 mcg/kg/min fixed-dose of dobutamine on cardiac function, microcirculation, gastric mucosal, hepatosplanchnic, and peripheral perfusion in septic shock patients.

Official Title
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Effects of Dobutamine on Microcirculation, Regional and Peripheral Perfusion in Septic Shock Patients.

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Dobutamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (>18 years) Septic shock for less than 24 hours Arterial lactate > 2.4 mmol/l Mechanical ventilation and pulmonary artery catheter in place Exclusion Criteria: Pregnancy Refractory hypotension Acute coronary syndrome within the last 3 months Previous use of dobutamine during the last 72 hours Cardiac index < 2.5 l/min/m2 Non-sinus rhythm Heart rate >140 BPM Anticipated surgery or dialytic procedure during the study period Child B or C liver cirrhosis Hemoglobin < 8 gr/dl Uncontrollable fever > 39ºC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dobutamine<br>Dobutamine at 5 mcg/kg/min will be administered for 2.5 hours | Drug: Dobutamine<br>* Dobutamine at 5 mcg/kg/min will be administered for 2.5 hours each. Measurements will be performed at baseline (within 30 minutes before starting the infusion) and repeated within the last 30 minutes of drug infusion.<br>* Other names: Dobutrex;|
| Placebo Comparator: Placebo<br>An equivalent infusion of placebo will be infused for 2.5 h | Drug: Placebo<br>* A 5% dextrose solution will be administered for 2.5 hours. Measurements will be performed at baseline (within 30 minutes before starting the infusion) and repeated within the last 30 minutes of drug infusion.<br>* Other names: Dextrose 5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the perfused vascular density | Perfused vessel density is a measure of sublingual microcirculation. It will be assessed with SDF videomicroscopy (Microscan ® for NTSC, Microvision Medical, Amsterdam, NL). (Crit Care 2007; 11:R101). | 2.5 h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macrohemodynamics | Macrohemodynamic values: mean arterial pressure, heart rate, and pulmonary artery catheter derived values (pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index) | 2.5 h | 
| Transthoracic echocardiography | Morphology and diameters of cardiac cavities Left ventricular systolic function Right ventricular systolic function left ventricular diastolic function | 2.5 h | 
| Gastric mucosal perfusion | Gastric mucosal perfusion: gastric air tonometry will be used to measure intraluminal pCO2 and calculate gastric - arterial pCO2 gradient (Tonocap, Datex) | 2.5 h | 
| Hepatosplanchnic blood flow | This will be assessed by the ICG-PDR method. Each patient will receive an ICG finger clip which will be connected to a liver function monitor (LiMon Pulsion Medical Systems, Germany). | 2.5 h | 
| Peripheral perfusion | Peripheral flow index (PFI), derived from the pulse oxymetry signal (MP20 IntelliVue monitor, Philips Medical systems, Amsterdam,NL) Temperatures at the blood (by PAC), and at different places in the skin. We will calculate central to toe gradient (Tc-toe), and forearm to fingertip skin temperature gradient (Tskin-diff) NIRS: Tissue oxygen saturation (StO2) will be measured by a tissue spectrometer (InSpectra Model 325, Hutchinson Technology, Hutchinson, Minn.) | 2.5 h | 
| Metabolic perfusion assessment | We will measure mixed venous O2 saturation and arterial lactate | 2.5 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock