Dobutamine does not influence inflammatory pathways during human endotoxemia.
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.


METHODS
Prospective, open-label study.


METHODS
Clinical research unit of a university hospital.


METHODS
Sixteen male healthy volunteers.


METHODS
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.


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.
Lemaire
Lucienne C
LC
Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
de Kruif
Martijn D
MD
Giebelen
Ida A
IA
Levi
Marcel
M
van der Poll
Tom
T
Heesen
Michael
M
D000328:Adult; D000704:Analysis of Variance; D001777:Blood Coagulation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D013566:Sympathomimetics / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D008070:Lipopolysaccharides; D013566:Sympathomimetics; D004280:Dobutamine