Β-Blockers IN SEPSIS

Abstract

Sepsis remains the leading cause for noncardiac intensive care unit deaths in the United States. Despite recent advances in the treatment of this devastating condition, mortality and morbidity remain unacceptably high. Sepsis is characterized by a multitude of pathophysiological changes that include inflammation, metabolic derangements, hemodynamic alterations, and multiorgan dysfunction. Unfortunately, several studies of treatment modalities aimed at correcting one or more of the underlying derangements have led to disappointing results. New treatment modalities are needed. beta-Receptor blockers have long been used for a variety of conditions such as coronary artery disease, congestive heart failure, and arterial hypertension. Recent data suggest that beta-blocker effects on metabolism, glucose homeostasis, cytokine expression, and myocardial function may be beneficial in the setting of sepsis. Although treating a potentially hypotensive condition with a drug with antihypertensive properties may initially seem counterintuitive, the metabolic and immunomodulatory properties of beta-blockers may be of benefit. It is the purpose of this review to discuss the effects of beta-blockers on the following: (1) metabolism, (2) glucose regulation, (3) the inflammatory response, (4) cardiac function, and (5) mortality in sepsis.

Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis

“…One of the major limitations of non-specific beta-blockade is a potential effect on local and systemic perfusion and in the clinical setting ICU physicians are constantly monitoring hemodynamics and adjusting treatment accordingly [13]. For this reason, this study was carried out with continuous cardiac monitoring.…”

“…These discrepancies in TNF-α expression are most likely due to the location and timing of cytokine measurement or the type of beta-receptor blocked. Sepsis has been described as displaying a variety of responses within the body compartments [29] and different microenvironments of the body are likely to see a relative increase or decrease in inflammatory cytokines due to sepsis [13]. Further, significant temporal changes in cytokine expression were observed in a rat CLP model of sepsis and timing of cytokine sampling must be considered [27].…”

“…Much of the recent experimental data on beta-blockers in sepsis have focused on the myocardial and whole body metabolic effects of propranolol in sepsis and injury [13]. Given the conflicting data on the effects of beta blockade during sepsis on metabolism, survival, cardiac performance and immune regulation, further studies, particularly studies examining other organs such as the lung, are needed.…”

Fundamental role of Warburg effect in various pathophysiological processes

“…Alpha 2 blocker Yohimbine (103) and beta blocker Esmolol (104) has been 509 used to treat cardiac dysfunction in sepsis animal models (11). Alpha 1 blocker Prazosin, beta 510 blocker Propranolol, MAPK inhibitor were used in reducing NO production by blocking the iNOS 511 in cardiomyocytes which was induced by norepinephrine with cytokine has been shown already 512 (40).…”

“…Many had already pointed out catecholamine 183 treatment carries risk in treating shock (30,34). In fact adrenergic blockers are already used long 184 time back in shock states in animals and in patients (10,11,30,35,36).We will see more about this 185 aspect in vascular dysfunction section. 186…”