Sympathetic Overstimulation During Critical Illness: Adverse Effects of Adrenergic Stress

Abstract

The term ''adrenergic'' originates from ''adrenaline'' and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ''fight-flight response'' is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.

Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

“…The plasma concentration of these methylarginines in renal transplant patients correlates inversely with the renal expression of alanine-glyoxylate aminotransferase 2 (26). ADMA is substantially raised in hyperthyroidism (27) and critical illness (28), that is, two conditions characterized by high sympathetic activity (29,30) and enhanced protein degradation (31,32), suggesting that reduced sympathetic activity after renal denervation may attenuate the release of these compounds from methylated proteins. Whether the sympathetic system regulates methylarginines by interfering with the synthesis or the degradation of these compounds remains to be investigated in future studies.…”

Beta Blockade Protection of Bone Marrow Following Trauma: The Role of G-CSF

“…This erythropoietic dysfunction can last for the duration of the patient's hospital stay regardless of the number of blood transfusions (8). Similarly, the adrenergic response to severe injury results in an elevation of catecholamine levels two to ten times normal (9)(10)(11). The cause of this persistent anemia is multifactorial but has been shown to be associated with a norepinephrine-induced prolonged suppression of BM erythroid cell growth (12).…”

Vasopressor hormones in shock—noradrenaline, vasopressin or angiotensin II: which one will make the race?

“…Their therapeutic safety margin is small (2). Dose dependently, adverse cardiac events occur in up to 50% of critically ill patients exposed to catecholamine therapy and are associated with an increase in both morbidity and mortality (3).…”