β1-Adrenergic Inhibition Improves Cardiac and Vascular Function in Experimental Septic Shock*

Kimmoun, Antoine; Louis, Huguette; Kattani, Narimane Al; Delemazure, Julie; Dessales, Nicolas; Wei, Chaojie; Marié, Pierre; Issa, Khodor; Lévy, Bruno

doi:10.1097/ccm.0000000000001078

Cited by 71 publications

(72 citation statements)

References 29 publications

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“…However, they failed to provide any supporting data, and one may argue that anti-inflammatory effects would unlikely have occurred this swiftly, i.e., after only four hours of treatment (12)(13)(14)(15).…”

Section: Study Design and Findingsmentioning

confidence: 99%

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Kimmoun¹,

Wei

Lévy³

et al. 2016

J. Thorac. Dis.

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Section: Study Design and Findingsmentioning

confidence: 99%

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Kimmoun¹,

Wei

Lévy³

et al. 2016

J. Thorac. Dis.

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“…Excessive adrenergic stimulation is harmful to the heart (3). In animal studies, esmolol, a selective beta-1-adrenergic blocker, improves cardiac contractility, stroke volume (SV) and vascular responsiveness to norepinephrine (4)(5)(6). In patients with septic shock who were initially stabilized, Morelli et al showed that esmolol infusion reduced heart rate, increased SV and reduced norepinephrine requirements (7).…”

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confidence: 99%

Beta-blockers in septic shock: a magnifying glass on the relation heart vessel

2016

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“…Analysis of a human database identified the upregulation of CAMP (p = 0.032) and TNFSF10 (p = 0.001) genes in septic patients compared with healthy controls [13]. In another animal model, esmolol decreased NFKB activation, increased Akt and endothelial nitric oxide synthase phosphorylation, while lowering inducible nitric oxide synthase expression in cardiac and vessel tissues [11]. Esmolol also improves LPS-induced ventricular dysfunction [14].…”

mentioning

confidence: 99%

“…A recent systematic review of beta-blockade in sepsis suggests some benefit, but there is still work to do because of the lack of large RCTs-most studies are small and uncontrolled case series/cohorts [7]. In addition to its beneficial effects on cardiac dynamics, beta-blockade may exert beneficial pleiotropic effects including blunting the inflammatory response, metabolic changes, and sepsis-associated coagulopathy [10][11][12][13][14]. Furthermore, beta-blockade may increase microcirculatory/small vessel blood flow in a small cohort (n = 25) of patients with sepsis [10].…”

mentioning

confidence: 99%

Beta-blockers in septic shock to optimize hemodynamics? Yes

2016

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Septic shock represents one of the maximum physical stresses to the organism. The physiological response to stress includes increased release of catecholamines, leading to a stimulation of cardiac β1-adrenergic receptors thereby increasing heart rate and ventricular contractility in order to increase global and microvascular blood flow and oxygen delivery to vital organs. Yet there are adverse effects of adrenergic stimulation including tachyarrhythmias, increased cardiac oxygen consumption with risk of cardiac ischemia, and immune dysregulation. So while it sounds at first contradictory to stabilize the cardiovascular function by giving β-blocking agents to "brake" the system, there could be benefits. However, is beta-blockade in these clinical circumstances really a brake?Dr. Morelli and coworkers present in a recent article in Intensive Care Medicine data on a cohort of 45 patients with the primary diagnosis of septic shock, in whom pulling this brake seems to improve cardiovascular function [1]. After initial hemodynamic stabilization over the first 24 h, patients who were tachycardic (heart rate more than 95 bpm) received a titrated esmolol infusion with the primary goal of reducing heart rate to 80-94 bpm within a time window of 4 h. Indeed, they achieved the intended reduction in heart rate, which could have primarily decreased cardiac output. However, the decreased heart rate was offset by increased ventricular filling time and volume, and decreased left ventricular afterload, ultimately resulting in increased stroke volume, obviously compensating for the decrease in heart rate. Interestingly, left ventricular ejection fraction remained unchanged. This, in combination with a decrease in arterial dP/dt max and a concomitant reduction in the need for norepinephrine, strongly points toward a more economical cardiac function under β-blockade. This mechanism is illustrated in Fig. 1.Similarly, β-blockade seemed paradoxical at first but was ultimately shown to be very effective in chronic heart failure [2]. To follow the automobile metaphor, β-blockade is more a shift to a higher gear, when revolutions per minute are becoming too high. This shift results in the same speed, but with greater fuel efficiency.So the physiological concept of improving cardiac efficiency seems to work as well in selected patients with septic shock. This is a very important message, since a physiological rationale is one indispensable prerequisite for any new treatment concept. With all enthusiasm, we have to keep in mind that this study performed in a selected group of patients without known cardiac comorbidities was not a randomized controlled trial (RCT), nor was any patient-centered clinical outcome assessed. Second, management of preload has an influence on that treatment concept: the automobile metaphor of changing gears works only with adequate engine cubic capacity. The parallel of engine cubic capacity in patients is cardiac preload that must be in the upper range-otherwise diastolic filling would not increase, when slowing ...

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β1-Adrenergic Inhibition Improves Cardiac and Vascular Function in Experimental Septic Shock*

Abstract: Adjunction of selective β1-blockade to standard septic shock management enhances intrinsic cardiac contractility and vascular responsiveness to catecholamines. These protective cardiovascular effects are likely predominantly attributed to the anti-inflammatory effect of esmolol.

Cited by 71 publications

References 29 publications

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Beta-blockers in septic shock: a magnifying glass on the relation heart vessel

Beta-blockers in septic shock to optimize hemodynamics? Yes

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