Beta-blockers in septic shock to optimize hemodynamics? Yes.

Abstract

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/dtmax 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 the heart rate—the major prerequisite for ejection fraction to remain stable leading to an increased stroke volume. Morelli and coworkers guaranteed high ventricular preload by keeping central venous pressure (CVP) ≥ 8 mmHg, and pulmonary arterial occlusion pressure (PAOP) ≥ 12 mmHg, following the current recommendations for the initial phase of fluid resuscitation in septic shock [3]. Using CVP and PAOP and in particular using those target values for guiding fluid therapy *Correspondence: dreuter@uke.de 1 Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center, Martinistr. 52, 20246 Hamburg, Germany Full author information is available at the end of the article