title: Prehospital resuscitation with phenylephrine in uncontrolled hemorrhagic shock and brain injury.
abstract: BACKGROUND
  Hypotension doubles the adverse outcome of severe brain injury (BI). This finding is thought to be due to secondary ischemia caused by cerebral hypoperfusion. Aggressive prehospital fluid resuscitation in BI is advocated to maintain mean arterial pressure (MAP). Increasing MAP by prehospital fluid resuscitation before control of hemorrhage is thought to increase blood loss and reduce survival. We hypothesized that vasoconstrictor treatment of uncontrolled hemorrhage would increase MAP, reduce hemorrhage volume, and decrease the extent of BI compared with delayed fluid resuscitation (DR) or resuscitation with Ringer's lactate (RL).
  
  
  METHODS
  Swine were randomly assigned to a control group or an experimental group: splenic laceration (uncontrolled hemorrhage) and cryogenic BI. The experimental group received one of three prehospital resuscitation regimens: DR, RL, or phenylephrine (Phen) to maintain baseline MAP. Variables were measured at baseline and at 20, 50, and 120 minutes during the simulated "prehospital and early hospital" phases and at 2 and 8 hours after surgical control of the uncontrolled hemorrhage. After killing, biopsies of the brain, liver, kidney, and gut were evaluated for histologic evidence of ischemia and compared between groups.
  
  
  RESULTS
  Hemorrhage volume was similar in the experimental groups. Mortality was lowest in the Phen group (11%) compared with DR (40%) and RL (33%) groups. Phen increased MAP and cerebral perfusion pressure. RL infusion increased cerebral blood flow and resulted in less secondary injury than either Phen or DR.
  
  
  CONCLUSIONS
  Phen improves MAP and systemic and cerebral perfusion pressure in the prehospital phase but does not reduce secondary neuronal ischemia. RL restores cerebral blood flow earlier and is associated with less secondary ischemia than either Phen or DR in this model. These data suggest that prehospital infusion of RL in patients with BI and shock is warranted and decreases secondary ischemia.
authors.affiliation: University of Vermont, Burlington 05401, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Alspaugh
authors.forename: K
authors.initials: K
authors.lastname: Sartorelli
authors.forename: S R
authors.initials: SR
authors.lastname: Shackford
authors.forename: E J
authors.initials: EJ
authors.lastname: Okum
authors.forename: S
authors.initials: S
authors.lastname: Buckingham
authors.forename: T
authors.initials: T
authors.lastname: Osler
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001706:Biopsy; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004632:Emergency Medical Services / Q000379:methods*; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D013552:Swine; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000316:Adrenergic alpha-Agonists; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D014662:Vasoconstrictor Agents; D010656:Phenylephrine