Dobutamine does not influence inflammatory pathways during human endotoxemia.

Abstract

OBJECTIVE:

Catecholamines have anti-inflammatory and anticoagulant properties. Dobutamine is a synthetic catecholamine frequently used in patients with septic myocardial dysfunction. The objective was to determine whether a continuous infusion of dobutamine exerts immunomodulatory effects in healthy volunteers challenged with endotoxin.

DESIGN:

Prospective, open-label study.

SETTING:

Clinical research unit of a university hospital.

PARTICIPANTS:

Sixteen male healthy volunteers.

INTERVENTIONS:

Volunteers received a constant infusion with dobutamine (10 microg.kg.min, n = 8) or physiologic saline (n = 8). All participants were challenged with a bolus injection of endotoxin prepared from Escherichia coli (4 ng/kg). Dobutamine infusion was commenced 1 hr before endotoxin challenge and was continued until 3 hrs thereafter.

MEASUREMENTS AND MAIN RESULTS:

Dobutamine infusion was associated with an increase in mean arterial blood pressure (peak 122 +/- 5 mm Hg) and heart rate (peak 84 +/- 4 beats/min, both p < .05 vs. saline). Endotoxin injection induced the systemic release of cytokines (tumor necrosis factor-alpha, interleukins-6, -8, and -10) and secretory phospholipase A2, endothelial cell activation (increase in the plasma levels of soluble E-selectin and von Willebrand factor), activation of coagulation (increased plasma levels of soluble tissue factor, F1 + 2 prothrombin fragment, and thrombin-antithrombin complexes), and activation with subsequent inhibition of fibrinolysis (increased plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin-alpha2-antiplasmin complexes). None of these responses were influenced by dobutamine.

CONCLUSIONS:

Dobutamine, infused in a clinically relevant dose, does not influence inflammatory and coagulant pathways during human endotoxemia.

• Authors: Lucienne C Lemaire, Martijn D de Kruif, Ida A Giebelen, Marcel Levi, Tom van der Poll, Michael Heesen
• Journal: Critical care medicine (Crit Care Med) Vol. 34 Issue 5 Pg. 1365-71 (May 2006) ISSN: 0090-3493 [Print] United States
• PMID: 16540959 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• Cytokines
• Lipopolysaccharides
• Sympathomimetics
• Dobutamine

Topics

• Adult
• Analysis of Variance
• Blood Coagulation (drug effects)
• Cytokines (blood, drug effects)
• Dobutamine (pharmacology, therapeutic use)
• Endothelium, Vascular (drug effects)
• Fibrinolysis (drug effects)
• Humans
• Immune System (drug effects)
• Lipopolysaccharides
• Male
• Prospective Studies
• Sepsis (drug therapy, immunology)
• Sympathomimetics (pharmacology, therapeutic use)