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

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.