Septic Shock
Conditions
Keywords
Septic shock
Brief summary
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
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.
Interventions
DRUGDobutamine
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.
DRUGPlacebo
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.
Sponsors
Pontificia Universidad Catolica de Chile
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the perfused vascular density | 2.5 h | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transthoracic echocardiography | 2.5 h | 1. Morphology and diameters of cardiac cavities 2. Left ventricular systolic function 3. Right ventricular systolic function 4. left ventricular diastolic function |
| Gastric mucosal perfusion | 2.5 h | Gastric mucosal perfusion: gastric air tonometry will be used to measure intraluminal pCO2 and calculate gastric - arterial pCO2 gradient (Tonocap, Datex) |
| Macrohemodynamics | 2.5 h | Macrohemodynamic values: mean arterial pressure, heart rate, and pulmonary artery catheter derived values (pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index) |
| Peripheral perfusion | 2.5 h | 1. Peripheral flow index (PFI), derived from the pulse oxymetry signal (MP20 IntelliVue monitor, Philips Medical systems, Amsterdam,NL) 2. 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) 3. NIRS: Tissue oxygen saturation (StO2) will be measured by a tissue spectrometer (InSpectra Model 325, Hutchinson Technology, Hutchinson, Minn.) |
| Metabolic perfusion assessment | 2.5 h | We will measure mixed venous O2 saturation and arterial lactate |
| Hepatosplanchnic blood flow | 2.5 h | 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). |
Countries
Chile
Outcome results
None listed