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

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 (α1-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.

• Authors: Ernesto Lopez, Osamu Fujiwara, Francisco Lima-Lopez, Oscar E Suman, Ronald P Mlcak, Hal K Hawkins, Robert A Cox, David N Herndon, Donald S Prough, Perenlei Enkhbaatar
• Journal: Critical care medicine (Crit Care Med) Vol. 44 Issue 2 Pg. e89-96 (Feb 2016) ISSN: 1530-0293 [Electronic] United States
• PMID: 26465218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adrenergic Agonists
• Proteins
• Water
• Epinephrine

Topics

• Adrenergic Agonists (pharmacology)
• Animals
• Epinephrine (administration & dosage, pharmacology)
• Female
• Fluid Therapy (methods)
• Hematologic Tests
• Hemodynamics
• Humans
• Hyperemia (physiopathology)
• Nebulizers and Vaporizers
• Prospective Studies
• Proteins (metabolism)
• Pulmonary Gas Exchange (drug effects)
• Random Allocation
• Respiration, Artificial
• Respiratory Mechanics
• Sheep
• Smoke Inhalation Injury (drug therapy, physiopathology)
• Water (metabolism)