Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock
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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/m2 at T + 180 min and T + 300 min, respectively, and decreased steadily from 45 (20) to 18 (13) ml/min/m2 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.
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- Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock
Intensive Care Medicine
Volume 37, Issue 8 , pp 1344-1351
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- Septic shock
- Beta blockade
- Animal model
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- Author Affiliations
- 1. Service de Réanimation, Hôpital Raymond Poincaré, AP-HP, Université de Versailles Saint Quentin, 104, bd. Raymond Poincaré, 92380, Garches, France
- 4. Laboratoire d’étude de la réponse neuroendocrine au sepsis- EA 4342, Université de Versailles Saint Quentin, Garches, France
- 2. Laboratoire de Biomathématiques-Biostatistique, EA 4275, Faculté de Pharmacie, Université de Nantes, 1, rue Gaston Veil, 44035, Nantes Cedex 1, France
- 3. Service de Réanimation, Hôpital Roger Salengro, CHRU, 59037, Lille, France