Bench-to-bedside review: Beta-adrenergic modulation in sepsis

Crit Care. 2009;13(5):230. doi: 10.1186/cc8026. Epub 2009 Oct 23.

Abstract

Sepsis, despite recent therapeutic progress, still carries unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, could be an interesting new therapeutic target for septic shock. Beta-adrenergic regulation of the immune function in sepsis is complex and is time dependent. However, beta2 activation as well as beta1 blockade seems to downregulate proinflammatory response by modulating the cytokine production profile. beta1 blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. Beta-blockers could also be of interest in the systemic catabolic response to sepsis, as they oppose epinephrine which is known to promote hyperglycemia, lipid and protein catabolism. The role of beta-blockers in coagulation is less clear cut. They could have a favorable role in the septic pro-coagulant state, as beta1 blockade may reduce platelet aggregation and normalize the depressed fibrinolytic status induced by adrenergic stimulation. Therefore, beta1 blockade as well as beta2 activation improves sepsis-induced immune, cardiovascular and coagulation dysfunctions. Beta2 blocking, however, seems beneficial in the metabolic field. Enough evidence has been accumulated in the literature to propose beta-adrenergic modulation, beta1 blockade and beta2 activation in particular, as new promising therapeutic targets for septic dyshomeostasis, modulating favorably immune, cardiovascular, metabolic and coagulation systems.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / immunology
  • Adrenergic beta-Antagonists / metabolism
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Blood Coagulation Disorders / drug therapy
  • Blood Coagulation Disorders / etiology
  • Critical Illness
  • Glucose Metabolism Disorders / drug therapy
  • Glucose Metabolism Disorders / etiology
  • Glucose Metabolism Disorders / physiopathology
  • Humans
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Ventricular Dysfunction / drug therapy
  • Ventricular Dysfunction / etiology
  • Ventricular Dysfunction / physiopathology

Substances

  • Adrenergic beta-Antagonists