Effects of Dobutamine on Microcirculation, Regional and Peripheral Perfusion in Septic Shock Patients
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Septic Shock |
Drug: Dobutamine Drug: Placebo |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | Effects of Dobutamine on Microcirculation, Regional and Peripheral Perfusion in Septic Shock Patients. |
- Change in the perfused vascular density [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]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).
- Macrohemodynamics [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]Macrohemodynamic values: mean arterial pressure, heart rate, and pulmonary artery catheter derived values (pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index)
- Transthoracic echocardiography [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]
- Morphology and diameters of cardiac cavities
- Left ventricular systolic function
- Right ventricular systolic function
- left ventricular diastolic function
- Gastric mucosal perfusion [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]Gastric mucosal perfusion: gastric air tonometry will be used to measure intraluminal pCO2 and calculate gastric - arterial pCO2 gradient (Tonocap, Datex)
- Hepatosplanchnic blood flow [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]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).
- Peripheral perfusion [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]
- 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.)
- Metabolic perfusion assessment [ Time Frame: 2.5 h ] [ Designated as safety issue: No ]We will measure mixed venous O2 saturation and arterial lactate
| Estimated Enrollment: | 20 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | October 2012 |
| Estimated Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Dobutamine
Dobutamine at 5 mcg/kg/min will be administered for 2.5 hours
|
Drug: Dobutamine
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.
Other Name: Dobutrex
|
|
Placebo Comparator: Placebo
An equivalent infusion of placebo will be infused for 2.5 h
|
Drug: Placebo
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.
Other Name: Dextrose 5%
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations| Contact: Glenn Hernandez, MD | 562 3543972 | glenn@med.puc.cl |
| Contact: Tomas Regueira, MD, PhD | 562 3543265 | tregueira@gmail.com |
| Chile | |
| Hospital Clinico Universidad Catolica de Chile | Recruiting |
| Santiago, RM, Chile, 6510260 | |
| Sub-Investigator: Guillermo Bugedo, MD | |
| Sub-Investigator: Tomas Regueira, MD, PhD | |
| Principal Investigator: Glenn Hernandez, MD | |
| Principal Investigator: | Glenn Hernandez, MD | Pontificia Universidad Catolica de Chile |
More Information
No publications provided
| Responsible Party: | Glenn Hernandez, Pontificia Universidad Catolica de Chile |
| ClinicalTrials.gov Identifier: | NCT01271153 History of Changes |
| Other Study ID Numbers: | 1100610 |
| Study First Received: | January 5, 2011 |
| Last Updated: | January 5, 2011 |
| Health Authority: | Chile: Comisión Nacional de Investigación Científica y Tecnológica |
Keywords provided by Pontificia Universidad Catolica de Chile:
|
Septic shock |
Additional relevant MeSH terms:
|
Shock, Septic Shock Pathologic Processes Sepsis Infection Systemic Inflammatory Response Syndrome Inflammation Dobutamine Cardiotonic Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions |
Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Adrenergic beta-1 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Protective Agents |
ClinicalTrials.gov processed this record on May 19, 2013