Beta-Adrenoreceptor Modulation of Metabolic, Endocrine and Immunologic Function During Critical Illness

Simon      James Barnes; Gareth      Lewis Ackland

Abstract

Acute critical illness is characterized by a hypermetabolic and catabolic response where profound endocrine, metabolic and immunologic changes are initiated and sustained through the activation, in part, of beta-adrenergic receptors. The modulation of beta-adrenergic receptor mediated endocrine, immunological and metabolic control may be beneficial in sepsis through a number of mechanisms. However, the complex interaction between beta-adrenoreceptormediated, apparently disparate systems may confer both positive and negative clinical outcomes. Chronic cardiac failure and sepsis/critical illness share several similar endocrine, immunologic and metabolic pathological features. Beneficial beta-adrenergic modulation of various pathophysiological changes has been demonstrated in both experimental and clinical heart failure. Investigations in critical illness rarely take into account the role of beta-adrenoreceptor stimulation in patients with such co-morbidities, who are among the most vulnerable to sepsis. Despite similar phenotypes and possibly common mechanisms, few clinical studies have explored whether beta-adrenoreceptor modulation may confer outcome benefit during critical illness. Recent experimental and observational clinical data illustrate that carefully monitored, patient/subject-specific beta-adrenoreceptor modulation may provide a useful intervention to ameliorate the detrimental effects of hyperacute and/or prolonged beta-adrenergic receptor stimulation. Most notably, human studies demonstrate that (non-specific) beta-adrenoreceptor blockade does not increase inflammation, sepsis, or infectious episodes. Furthermore, hemodynamically tailored beta-1 adrenoreceptor antagonism improves outcome in experimental sepsis through novel cardiac and non-cardiac mechanisms. Understanding the dynamic complexity of beta-adrenergic physiology during critical illness offers further insights into the mechanisms underlying maladaptive metabolic and immunologic changes and potentially novel therapeutic interventions.

Keywords: beta-adrenoreceptor, catecholamine, critical illness, endocrine, immune, metabolism, sepsis

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