Superior Effects of Nebulized Epinephrine to Nebulized Albuterol and Phenylephrine in Burn and Smoke Inhalation-Induced Acute Lung Injury

Satoshi Fukuda, Ernesto Lopez, Koji Ihara, Yosuke Niimi, Clark R Andersen, Sam Jacob, Robert A Cox, Jose D Rojas, Donald S Prough, Perenlei Enkhbaatar
Shock 2020 June 23
The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. The present study compared the effects of epinephrine, phenylephrine, and albuterol on a model of BSI-ALI. We tested the hypothesis that both α1- and β2-agonist effects are required for ameliorating more efficiently the BSI-ALI. Forty percent of total body surface area, 3-degree cutaneous burn, and 48-breaths of cotton smoke inhalation were induced to 46 female Merino sheep. Post-injury, sheep were mechanically ventilated and cardiopulmonary hemodynamics were monitored for 48-hours. Sheep were allocated into groups: 1) control, n = 17; 2) epinephrine, n = 11; 3) phenylephrine, n = 6; and 4) albuterol, n = 12. The drug nebulization began 1-hour post-injury and was repeated every 4 hours thereafter. In the results, epinephrine group significantly improved oxygenation compared to other groups, and significantly reduced pulmonary vascular permeability index, lung wet-to-dry weight ratio, and lung tissue growth factor-β1 level compared to albuterol and control groups. Epinephrine and phenylephrine groups significantly reduced trachea wet-to-dry weight ratio and lung vascular endothelial growth factor-A level compared to control group. Histopathologically, epinephrine group significantly reduced lung severity scores and preserved vascular endothelial-cadherin level in pulmonary arteries. In conclusion, the results of our studies suggest that nebulized epinephrine more effectively ameliorated the severity of BSI-ALI than albuterol or phenylephrine, possibly by its combined α1- and β2-agonist properties.

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