title: Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice.
abstract: BACKGROUND
  Norepinephrine administration is controversial during hemorrhagic shock resuscitation to stabilize mean arterial pressure (MAP) level because it could have deleterious effects on local circulations. The authors investigated the effect of norepinephrine on intestinal microcirculation during fluid resuscitation in uncontrolled hemorrhagic shock.
  
  
  METHODS
  Mice (n = 6 per group) submitted to an uncontrolled hemorrhagic shock by tail section were randomly assigned to a resuscitation with fluid but without norepinephrine to target a MAP level of 50 mmHg (FR50) or 60 mmHg (FR60) or a resuscitation with fluid and norepinephrine to target a MAP level of 50 mmHg (FRNE50) or 60 mmHg (FRNE60). Intestinal microcirculation was observed by intravital microscopy.
  
  
  RESULTS
  Fluid requirements were lower in groups resuscitated with fluid and norepinephrine than in groups resuscitated with fluid without norepinephrine (74.6 ± 45.1 in FR50 vs. 28.1 ± 10.0 µl/g in FRNE50; P = 0.004 and 161.9 ± 90.4 in FR60 vs. 44.5 ± 24.0 µl/g in FRNE60; P = 0.041). Blood loss was not statistically different between FR50 and FRNE50 (14.8 ± 8.3 vs. 8.5 ± 2.9 µl/g; P = 0.180) but was significantly lower in FRNE60 than in FR60 (10.1 ± 4.2 vs. 22.6 ± 9.6 µl/g; P = 0.015). This beneficial effect was associated with the restoration of intestinal microcirculation to the same extent in fluid resuscitated groups without norepinephrine (FR50 and FR60) and fluid resuscitated groups with norepinephrine (FRNE50 and FRNE60).
  
  
  CONCLUSIONS
  During MAP-directed resuscitation of uncontrolled hemorrhagic shock, the administration of norepinephrine decreased blood loss and fluid requirements while preserving intestinal villi microcirculation.
authors.affiliation: From the Laboratoire d'Etude de la Microcirculation, Université Paris VII Lariboisère St-Louis, UMR 942, Paris, France (A.H., N.B., H.K., L.D., E.V., J.D.); Service d'Anesthésie-Réanimation Chirurgicale, Hôpital de Bicêtre, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France (A.H., O.H., J.D.); Baker IDI Heart and Diabetes Institute, Monash University, Melbourne, Australia (O.H.); Service de Réanimation Pédiatrique, Hôpital Necker Enfants-Malades, Assistance Publique, Hôpitaux de Paris, Faculté de Médecine, Université Paris-Descartes, Paris, France (L.D.); Service d'Anatomie Pathologique, Groupe Hospitalier Paris-Seine-Saint Denis, Hopital Jean Verdier, AP-HP, Bondy, France (M.L., M.Z.); and Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, Bobigny, France (M.L., M.Z.).
authors.forename: Anatole
authors.initials: A
authors.lastname: Harrois
authors.forename: Nathalie
authors.initials: N
authors.lastname: Baudry
authors.forename: Olivier
authors.initials: O
authors.lastname: Huet
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kato
authors.forename: Laurent
authors.initials: L
authors.lastname: Dupic
authors.forename: Manuel
authors.initials: M
authors.lastname: Lohez
authors.forename: Marianne
authors.initials: M
authors.lastname: Ziol
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Jacques
authors.initials: J
authors.lastname: Duranteau
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001784:Blood Gas Analysis; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D005440:Fluid Therapy / Q000379:methods*; D007413:Intestinal Mucosa / Q000098:blood supply*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D009638:Norepinephrine