Beta-blocker use in severe sepsis and septic shock: a systematic review

Sanfilippo, Filippo; Santonocito, Cristina; Morelli, Andrea; Foëx, P.

doi:10.1185/03007995.2015.1062357

Cited by 78 publications

(60 citation statements)

References 65 publications

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“…While it is theoretically plausible, experimental and clinical studies yielded conflicting results (5)(6)(7)48,49). Observational studies showed that esmolol, the most commonly used beta-blocker in septic shock, was associated with economization of cardiac work and oxygen consumption.…”

Section: Beta-blockersmentioning

confidence: 99%

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Vasoactive agents for the treatment of sepsis

Zhang

Chen

2016

Ann. Transl. Med.

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The article describes some commonly used vasoactive agents in patients with septic shock. Depending on their distinct pharmacological properties, their effects on vascular bed and cardiac function are different. For example, dopamine has equivalent effect on heart and vasculature, which can result in increases in cardiac output, mean arterial pressure and heart rate. Dobutamine is considered as inodilator because it has potent effect on cardiac systole and vasculature. Patients with sepsis and septic shock sometimes have coexisting cardiac dysfunction that justifies the use of dobutamine. Levosimendan is a relatively new agent exerting its inodilator effect by increasing sensitivity of myocardium to calcium. Some preliminary studies showed a promising result of levosimendan on reducing mortality.

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Section: Beta-blockersmentioning

confidence: 99%

“…Since it remains largely unknown whether such response is an adaptation to noxious stimulus or a maladaption to it, a variety of drugs have been used for the management of cardiovascular presentations of sepsis, severe sepsis or septic shock (5)(6)(7). In this review, we aimed to discuss vasoactive agents that can be used to treat sepsis.…”

Section: Introductionmentioning

confidence: 99%

Vasoactive agents for the treatment of sepsis

Zhang

Chen

2016

Ann. Transl. Med.

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“…Beta-blockade has been associated with reduced mortality during septic shock in experimental studies and in two preliminary human RCTs [6][7][8]. A recent small pilot RCT (n = 90) in China suggested benefit of the combination of esmolol and milrinone in sepsis for control of heart rate and possibly survival (but the absolute risk reduction was an unlikely 30 %) [6].…”

mentioning

confidence: 99%

“…Retrospective cohort studies suggest that chronic use of beta-blockers prior to ICU admission improves short-term survival [9]. 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].…”

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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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“…In the present issue of CMRO, Sanfilippo et al 1 discuss the results of a systematic review on the use of beta blockade in patients with severe sepsis or septic shock. The authors found only two randomized controlled trials (RCTs) including a total of 195 patients, a few small prospective and retrospective studies and several experimental studies.…”

mentioning

confidence: 99%