Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00134212
Recruitment Status : Completed
First Posted : August 24, 2005
Last Update Posted : January 2, 2006
Information provided by:
Rennes University Hospital

Brief Summary:

In septic shock, when volume resuscitation fails to restore mean arterial pressure, catecholamines such as dopamine, dobutamine, epinephrine, or norepinephrine are used, either alone or in combination. Although they allow hemodynamic success to be obtained, they can leave some regional blood flows impaired, especially the hepatosplanchnic perfusion, which contributes to multiple organ failure.

Dopexamine is a structural and synthetic analog of dopamine that exerts systemic and gut vasodilation and stimulates cardiac contraction. In experimental models, dopexamine has been shown to exert anti-inflammatory properties and to protect the hepatic ultra structure. The combination of dopexamine and norepinephrine could therefore constitute an interesting alternative in treating septic shock patients. This study will test the efficacy (on gastric mucosal blood flow, hepatic damage and oxidative stress) and safety of the combination of dopexamine and norepinephrine (compared to those of epinephrine alone) in the treatment of patients with septic shock.

Condition or disease Intervention/treatment Phase
Septic Shock Drug: Dopexamine and norepinephrine Drug: Epinephrine Phase 2

Detailed Description:

Objective: To compare the combination of dopexamine and norepinephrine with epinephrine alone on gastric mucosal blood flow (GMBF), hepatic damage and oxidative stress in septic shock.

Setting: Surgical intensive care unit in a university hospital.

Design: Prospective, randomized, controlled study on 2 parallel groups.

Patients: Adults fulfilling usual criteria for septic shock.

Interventions: Systemic hemodynamics, GMBF (laser-Doppler), plasma α-glutathione S-transferase, aspartate aminotransferase, alanine aminotransferase and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70-80 mmHg (T1), and 2 (T2) and 6 (T3) hours after T1. Drugs were titrated from 0.2 µg/kg/min with 0.2 µg/kg/min increments every 3 min for epinephrine and norepinephrine, and from 0.5 µg/kg/min with 0.5 µg/kg/min increments every 3 min for dopexamine.

Study Type : Interventional  (Clinical Trial)
Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Primary Purpose: Treatment
Official Title: Prospective, Randomized Study on Two Parallel Groups Comparing Dopexamine and Norepinephrine in Combination to Epinephrine Alone on Systemic and Pulmonary Hemodynamics, Gastric Mucosal Perfusion, and Oxidative Stress in Septic Shock
Study Start Date : March 2002
Study Completion Date : June 2004

Primary Outcome Measures :
  1. Gastric mucosal blood flow assessed using a laser-Doppler flowmeter

Secondary Outcome Measures :
  1. Systemic and pulmonary hemodynamics: systolic, diastolic and mean arterial, right atrial, systolic, diastolic and mean pulmonary arterial, and pulmonary capillary wedge pressures
  2. heart rate, stroke volume, cardiac output
  3. systemic and pulmonary vascular resistances
  4. arterial and venous blood gases and arterial lactate
  5. alanine and aspartate amino transferases
  6. bilirubin
  7. α-glutathione S-transferase
  8. nitric oxide and reactive oxygen species productions

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adults over 18 years
  • Informed consent
  • Septic shock with:

    • evidence of infection;
    • at least 3 of the following criteria: temperature > 38°C or < 36.5°C; respiratory rate > 20 breaths per minute or PaCO2 < 32 mmHg or mechanical ventilation; heart rate > 90 beats/min; white blood cell count > 12,000/mm3 or < 4,000/mm3;
    • at least 2 of the following criteria: plasma lactate > 2 mmol/L or unexplained metabolic acidosis (pH < 7.3); hypoxemia defined by PaO2 < 70 mmHg at room air or a PaO2/FiO2 ratio < 280 mmHg (or < 200 mmHg if pneumonia was the source of sepsis) or need for mechanical ventilation; urine output < 30 mL/h for at least 2 hours despite a fluid challenge of at least 500mL; a platelet count < 100,000/mm3, a decrease of 50% from previous value, or unexplained coagulopathy (prothrombin time < 60% and elevated fibrin degradation products > 10 μg/mL);
    • systolic blood pressure < 90 mmHg despite an optimal volume loading defined by a pulmonary capillary wedge pressure > 12 mmHg.

Exclusion Criteria:

  • Pregnant women
  • Patients with a history of esophageal or gastric disease
  • Patients with a history of esophageal or gastric surgery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00134212

Rennes University Hospital
Rennes, France, 35033
Sponsors and Collaborators
Rennes University Hospital
Study Director: Yannick Mallédant, MD Rennes University Hospital
Study Chair: Eric Bellissant, MD, PhD Rennes University Hospital
Principal Investigator: Philippe Seguin, MD Rennes University Hospital

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00134212     History of Changes
Other Study ID Numbers: AFSSAPS 020193
First Posted: August 24, 2005    Key Record Dates
Last Update Posted: January 2, 2006
Last Verified: December 2005

Keywords provided by Rennes University Hospital:
Splanchnic perfusion, hepatic damage, oxidative stress.

Additional relevant MeSH terms:
Shock, Septic
Pathologic Processes
Systemic Inflammatory Response Syndrome
Epinephryl borate
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Vasoconstrictor Agents
Vasodilator Agents
Dopamine Agonists