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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Pontificia Universidad Catolica de Chile.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier:
NCT01271153
First received: January 5, 2011
Last updated: NA
Last verified: September 2010
History: No changes posted
  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.

Resource links provided by NLM:


Further study details as provided by Pontificia Universidad Catolica de Chile:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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 ]
    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 [ 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 ]
    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 [ 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271153

Contacts
Contact: Glenn Hernandez, MD 562 3543972 glenn@med.puc.cl
Contact: Tomas Regueira, MD, PhD 562 3543265 tregueira@gmail.com

Locations
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         
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
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
Shock, Septic
Infection
Inflammation
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Dobutamine
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014