Beta-adrenoreceptor modulation of metabolic, endocrine and immunologic function during critical illness.
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-adrenoreceptor-mediated, 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.
Barnes
Simon James
SJ
Department of Medicine, Wolfson Institute for Biomedical Research, Wing 3.2, Cruciform Building, Gower Street, University College London, London WC1E 6BT, UK.
Ackland
Gareth Lewis
GL
D000818:Animals; D016638:Critical Illness; D004703:Endocrine System / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000276:immunology* / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta