title: Vasopressors and inotropes in the treatment of human septic shock: effect on innate immunity?
abstract: Catecholamines have been suggested to modulate innate immune responses in experimental settings. The significance hereof in the treatment of human septic shock is unknown. We therefore sought if and how vasopressor/inotropic doses relate to pro-inflammatory mediators during treatment of septic shock. We prospectively studied 20 consecutive septic shock patients. For 3 days after admission, hemodynamic variables, lactate and plasma levels of interleukins (IL)-6 and 8, tumor necrosis factor (TNF)-α, and elastase-α(1)-antitrypsin were measured six hourly. Doses of vasoactive drugs were recorded. Of the 20 patients, nine died in the intensive care unit. Dobutamine doses were positively associated and related to TNF-α plasma levels, independently of disease severity, hemodynamics, and outcome, in multivariable models. Dopamine doses were positively associated with IL-6, and norepinephrine was inversely associated with IL-8 and TNF-α levels. Our observations suggest that catecholamines used in the treatment of human septic shock differ in their potential modulation of the innate immune response to sepsis in vivo. Dobutamine treatment may contribute to circulating TNF-α and dopamine to IL-6, independently of activated neutrophils. Conversely, norepinephrine may lack pro-inflammatory actions.
authors.affiliation: Department of Intensive Care and Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. kjhartemink@hetnet.nl
authors.forename: Koen J
authors.initials: KJ
authors.lastname: Hartemink
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use; D004298:Dopamine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D009638:Norepinephrine / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D002316:Cardiotonic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D004280:Dobutamine; D019272:Leukocyte Elastase; D004298:Dopamine; D009638:Norepinephrine