Adrenergic modulation and heart failure during sepsis: place of beta-blockers

Abstract

Despite recent therapeutic progress, sepsis is still responsible for unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, may be an interesting new therapeutic target for septic shock. β-adrenergic regulation of the immune function in sepsis is complex and time-dependent. However, β2 activation as well as β1 blockade seem to downregulate the pro-inflammatory response by modulating the cytokine production profile. β1 blockade improves cardiovascular homeostasis in septic animals by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. β-blockers may also be of interest in the systemic catabolic response to sepsis, as they counteract epinephrine, which is known to promote hyperglycemia as well as lipid and protein catabolism. β1 blockade, and β2 activation improve sepsis-induced immune, cardiovascular, and coagulation dysfunctions. However, β2 blockade seems beneficial regarding metabolism. Enough evidence has been accumulated in the literature to propose β-adrenergic modulation, β1 blockade, and β2 activation in particular, as new promising therapeutic targets for septic dyshomeostasis, altering favourably immune, cardiovascular, metabolic, and coagulation systems.