Dopexamine and Norepinephrine Compared With Epinephrine Alone in Septic Shock

NCT ID: NCT00134212

Last Updated: 2006-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-03-31
• Study Completion Date: 2004-06-30

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.

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Interventions

Dopexamine and norepinephrine

Intervention Type: DRUG

Epinephrine

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Yannick Mallédant, MD

Role: STUDY_DIRECTOR

Rennes University Hospital

Eric Bellissant, MD, PhD

Role: STUDY_CHAIR

Rennes University Hospital

Philippe Seguin, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Rennes University Hospital

Rennes, , France

Countries

France

References

Schmidt W, Hacker A, Gebhard MM, Martin E, Schmidt H. Dopexamine attenuates endotoxin-induced microcirculatory changes in rat mesentery: role of beta2 adrenoceptors. Crit Care Med. 1998 Oct;26(10):1639-45. doi: 10.1097/00003246-199810000-00012.

Reference Type: BACKGROUND

PMID: 9781719 (View on PubMed)

Tighe D, Moss R, Heywood G, al-Saady N, Webb A, Bennett D. Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis. Crit Care Med. 1995 Dec;23(12):1997-2007. doi: 10.1097/00003246-199512000-00008.

Reference Type: BACKGROUND

PMID: 7497722 (View on PubMed)

Seguin P, Laviolle B, Guinet P, Morel I, Malledant Y, Bellissant E. Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]. Crit Care. 2006 Feb;10(1):R32. doi: 10.1186/cc4827.

Reference Type: DERIVED

PMID: 16507156 (View on PubMed)

Other Identifiers

LOC-H/01-08

Identifier Type: -

Identifier Source: secondary_id

CIC0203/008

Identifier Type: -

Identifier Source: secondary_id

AFSSAPS 020193

Identifier Type: -

Identifier Source: org_study_id