Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine with Burn and Smoke Inhalation Injury

Ernesto Lopez, Osamu Fujiwara, Francisco Lima-Lopez, Oscar Suman, Ronald P. Mlcak, Hal K. Hawkins, Robert A. Cox, David Herndon, Donald Prough, Perenlei Enkhbaatar

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Abstract

Objectives: To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (β2-adrenergic receptor agonism) and attenuation of airway hyperemia (1-adrenergic receptor agonism) with minimal systemic effects. Design: Randomized, controlled, prospective, and large animal translational studies. Setting: University large animal ICU. Subjects: Twelve chronically instrumented sheep. Interventions: 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. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)e89-e96
JournalCritical Care Medicine
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2016

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Keywords

  • Acute respiratory distress syndrome
  • Airway hyperemia
  • Burn and smoke inhalation
  • Epinephrine
  • Vascular permeability

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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