Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock

Abstract

The aim of this experimental study is to investigate cardiovascular tolerance of blockade of beta-adrenergic receptors in an endotoxin model. Prospective, randomized, controlled study. Animal laboratory in a university medical center. Ten anesthetized, mechanically ventilated pigs were challenged with intravenous lipopolysaccharide (LPS) to achieve a status of profound hypodynamic shock. Systemic and pulmonary hemodynamics and cardiac output were continuously monitored throughout the 5-h study period, and blood samples were taken at baseline (T - 30 min), 1 h from the beginning of LPS infusion (T + 60 min), and every 2 h (T + 180 min and T + 300 min). Animals were randomly assigned to continuous intravenous esmolol infusion titrated to decrease heart rate by 20% or isotonic saline. Esmolol decreased heart rate by 20%, while in the saline group, heart rate increased by 7% and 22% at T + 180 min and T + 300 min, respectively (p < 0.001). In esmolol-treated animals, cardiac index decreased by 9% at T + 180 min and by 2% at T + 300 min, and in controls by 14% at T + 180 min and by 27% at T + 300 min (p = 0.870). In esmolol-treated animals, median (interquartile range, IQR) stroke index was 31 (6) and 47 (11) ml/min/m(2) at T + 180 min and T + 300 min, respectively, and decreased steadily from 45 (20) to 18 (13) ml/min/m(2) in controls (p = 0.030). There were no significant differences between groups for any other hemodynamics variables, except for systemic vascular resistance (SVR) (p = 0.017). In large animals with endotoxemic shock, continuous infusion of esmolol, a selective beta-1 adrenergic blocker, titrated to decrease heart rate by 20%, was well tolerated and may offset LPS-induced cardiac dysfunction by a preload positive effect.