Beta-Adrenergic Blockade in Critical Illness

Abstract

Catecholamine upregulation is a core pathophysiological feature in critical illness. Sustained catecholamine β-adrenergic induction produces adverse effects relevant to critical illness management. β-blockers (βB) have proposed roles in various critically ill disease states, including sepsis, trauma, burns, and cardiac arrest. Mounting evidence suggests βB improve hemodynamic and metabolic parameters culminating in decreased burn healing time, reduced mortality in traumatic brain injury, and improved neurologic outcomes following cardiac arrest. In sepsis, βB appear hemodynamically benign after acute resuscitation and may augment cardiac function. The emergence of ultra-rapid βB provides new territory for βB, and early data suggest significant improvements in mitigating atrial fibrillation in persistently tachycardic septic patients. This review summarizes the evidence regarding the pharmacotherapeutic role of βB on relevant pathophysiology and clinical outcomes in various types of critical illness.

Keywords: beta-blockers; critical illness; esmolol; hemodynamics; sepsis; tachyarrhythmia.

FIGURE 1

Physiologic response to β-adrenergic receptor agonism and antagonism in critical illness. The catecholamine response characterized by epinephrine, norepinephrine, and dopamine release result in stimulation of β1 (majorly) and β2 (minorly). In contrast, β3 agonism blunts the catecholamine response. The physiologic response to β1, β2, and β3 agonism culminates in numerous negative effects within critical illness that can ultimately lead to negative clinical outcomes including increased mortality. This introduces the beneficial physiologic response of βB antagonism as a way to mediate the detrimental effects of the hyperadrenergic state prominent in various types of critical illness. Illustration created with BioRender.com.

FIGURE 2

Hemodynamic effects of sepsis and β-Blockade. In panel A, the stroke volume (SV) and cardiac output (CO), stroke volume (SV), and heart rate (HR) of a normal, healthy individual are presented. In panel B, due to the negative inotropy associated with βB, which causes reduced HR, the overall CO is reduced despite normal SV. In panel C, sepsis results in tachycardia, due to excessive sympathetic activation. This increase in HR does not allow for adequate ventricular filling causing a decrease in CO secondary to a decrease in SV. In panel D, given that venous return (i.e., preload) is adequate, then βB-induced HR reduction allows for more left ventricular filling time, subsequently decreasing afterload and increasing SV enough to overcome decreased HR and improved CO.