title: Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine With Burn and Smoke Inhalation Injury.
abstract: OBJECTIVE
  To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (β2-adrenergic receptor agonism) and attenuation of airway hyperemia (α1-adrenergic receptor agonism) with minimal systemic effects.
  
  
  METHODS
  Randomized, controlled, prospective, and large animal translational studies.
  
  
  METHODS
  University large animal ICU.
  
  
  METHODS
  Twelve chronically instrumented sheep.
  
  
  METHODS
  The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6.
  
  
  RESULTS
  Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment.
  
  
  CONCLUSIONS
  Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.
authors.affiliation: 1Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX. 2Department of Surgery, University of Texas Medical Branch, and Shriners Hospital for Children, Galveston, TX. 3Department of Respiratory Care, University of Texas Medical Branch, and Shriners Hospital for Children, Galveston, TX. 4Department of Pathology, University of Texas Medical Branch, and Shriners Hospital for Children, Galveston, TX.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lopez
authors.forename: Osamu
authors.initials: O
authors.lastname: Fujiwara
authors.forename: Francisco
authors.initials: F
authors.lastname: Lima-Lopez
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Suman
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mlcak
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Donald S
authors.initials: DS
authors.lastname: Prough
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006403:Hematologic Tests; D006439:Hemodynamics; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D009330:Nebulizers and Vaporizers; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D012121:Respiration, Artificial; D015656:Respiratory Mechanics; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000503:physiopathology*; D014867:Water / Q000378:metabolism*
chemical_list: D000322:Adrenergic Agonists; D011506:Proteins; D014867:Water; D004837:Epinephrine