title: Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model.
abstract: BACKGROUND
  Esmolol may efficiently reduce heart rate (HR) and decrease mortality during septic shock. An improvement of microcirculation dissociated from its macrocirculatory effect may a role. The present study investigated the effect of esmolol on gut and sublingual microcirculation in a resuscitated piglet model of septic shock.
  
  
  METHODS
  Fourteen piglets, anesthetized and mechanically ventilated, received a suspension of live Pseudomonas aeruginosa. They were randomly assigned to two groups: the esmolol (E) group received an infusion of esmolol, started at 7.5 μg⋅kg(-1)⋅min(-1), and progressively increased to achieve a HR below 90 beats⋅min(-1). The control (C) group received an infusion of Ringer's lactate solution. HR, mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), arterio-venous blood gas and lactate were recorded. Oxygen consumption (VO2), delivery (DO2) and peripheral extraction (O2ER) were computed. Following an ileostomy, a laser Doppler probe was applied on ileal mucosa to monitor gut microcirculatory laser Doppler flow (GMLDF). Videomicroscopy was also used on ileal mucosa and sublingual areas to evaluate mean flow index (MFI), heterogeneity, ratio of perfused villi and proportion of perfused vessels. Resuscitation maneuvers were performed following a defined algorithm.
  
  
  RESULTS
  Bacterial infusion induced a significant alteration of the gut microcirculation with an increase in HR. Esmolol produced a significant time/group effect with a decrease in HR (P <0.004) and an increase in SVR (P <0.004). Time/group effect was not significant for CI and MAP, but there was a clear trend toward a decrease in CI and MAP in the E group. Time/group effect was not significant for SI, O2ER, DO2, VO2, GMLDF and lactate. A significant time/group effect of ileal microcirculation was found with a lower ileal villi perfusion (P <0.025) in the C group, and a trend toward a better MFI in the E group. No difference between both groups was found regarding microcirculatory parameters in the sublingual area.
  
  
  CONCLUSIONS
  Esmolol provided a maintenance of microcirculation during sepsis despite its negative effects on macrocirculation. Some parameters even showed a trend toward an improvement of the microcirculation in the gut area in the esmolol group.
authors.affiliation: Service d'anesthésie-réanimation, Hospices Civils de Lyon, Hôpital Edouard-Herriot, 5 place d'Arsonval, 69437, Lyon, Cedex 03, France. matthias.jl@gmail.com.
authors.forename: Matthias
authors.initials: M
authors.lastname: Jacquet-Lagrèze
authors.affiliation: Service d'anesthésie-réanimation, Hospices Civils de Lyon, Hôpital Edouard-Herriot, 5 place d'Arsonval, 69437, Lyon, Cedex 03, France. bernard.allaouchiche@chu-lyon.fr.|Université Claude-Bernard, Lyon 1. Campus Lyon Santé Est, 8 avenue Rockefeller, 69008, Lyon, France. bernard.allaouchiche@chu-lyon.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
authors.affiliation: EA 4174 Sepsis Inflammation Hémostase, Université de Lyon, VetAgro Sup - Campus Vétérinaire de Lyon, 1 Avenue Bourgelat, 69280, Marcy-l'Étoile, France. damien.restagno@vetagro-sup.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Restagno
authors.affiliation: EA 4174 Sepsis Inflammation Hémostase, Université de Lyon, VetAgro Sup - Campus Vétérinaire de Lyon, 1 Avenue Bourgelat, 69280, Marcy-l'Étoile, France. christian.paquet@vetagro-sup.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Paquet
authors.affiliation: EA 4174 Sepsis Inflammation Hémostase, Université de Lyon, VetAgro Sup - Campus Vétérinaire de Lyon, 1 Avenue Bourgelat, 69280, Marcy-l'Étoile, France. jean-yves.ayoub@vetagro-sup.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Ayoub
authors.affiliation: Université Claude-Bernard, Lyon 1. Campus Lyon Santé Est, 8 avenue Rockefeller, 69008, Lyon, France. jerome.etienne@univ-lyon1.fr.|Laboratory of Microbiology, Groupement Hospitalier Est, 59 Boulevard Pinel, 69500, Bron, France. jerome.etienne@univ-lyon1.fr.
authors.forename: Jêrome
authors.initials: J
authors.lastname: Etienne
authors.affiliation: Université Claude-Bernard, Lyon 1. Campus Lyon Santé Est, 8 avenue Rockefeller, 69008, Lyon, France. francois.vandenesch@univ-lyon1.fr.|Laboratory of Microbiology, Groupement Hospitalier Est, 59 Boulevard Pinel, 69500, Bron, France. francois.vandenesch@univ-lyon1.fr.
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Laboratory of Microbiology, Groupement Hospitalier Est, 59 Boulevard Pinel, 69500, Bron, France. olivier.dauwalder@chu-lyon.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dauwalder
authors.affiliation: EA 4174 Sepsis Inflammation Hémostase, Université de Lyon, VetAgro Sup - Campus Vétérinaire de Lyon, 1 Avenue Bourgelat, 69280, Marcy-l'Étoile, France. jeanne-marie.bonnet@vetagro-sup.fr.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Bonnet
authors.affiliation: EA 4174 Sepsis Inflammation Hémostase, Université de Lyon, VetAgro Sup - Campus Vétérinaire de Lyon, 1 Avenue Bourgelat, 69280, Marcy-l'Étoile, France. stephane.junot@vetagro-sup.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Junot
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D065568:Oral Mucosal Absorption / Q000187:drug effects / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D013361:Sublingual Gland / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D013552:Swine
chemical_list: D011412:Propanolamines; C036604:esmolol