title: Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock.
abstract: OBJECTIVE
  The aim of this experimental study is to investigate cardiovascular tolerance of blockade of beta-adrenergic receptors in an endotoxin model.
  
  
  METHODS
  Prospective, randomized, controlled study.
  
  
  METHODS
  Animal laboratory in a university medical center.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Réanimation, Hôpital Raymond Poincaré, AP-HP, Université de Versailles Saint Quentin, 104, bd. Raymond Poincaré, 92380 Garches, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Aboab
authors.forename: Veronique
authors.initials: V
authors.lastname: Sebille
authors.forename: Mercé
authors.initials: M
authors.lastname: Jourdain
authors.forename: Jacques
authors.initials: J
authors.lastname: Mangalaboyi
authors.forename: Miloud
authors.initials: M
authors.lastname: Gharbi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mansart
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008991:Monitoring, Physiologic; D011412:Propanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D011446:Prospective Studies; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D008070:Lipopolysaccharides; D011412:Propanolamines; C036604:esmolol