Preclinical evaluation of epinephrine nebulization to reduce airway hyperemia and improve oxygenation after smoke inhalation injury.

Abstract

OBJECTIVE:

Acute lung injury secondary to smoke inhalation is a major source of morbidity and mortality in burn patients. We tested the hypothesis that nebulized epinephrine would ameliorate pulmonary dysfunction secondary to acute lung injury by reducing airway hyperemia and edema formation and mediating bronchodilatation in an established, large animal model of inhalation injury.

DESIGN:

Prospective, controlled, randomized trial.

SETTING:

University research laboratory.

SUBJECTS:

Twenty-four chronically instrumented, adult, female sheep.

INTERVENTIONS:

Following baseline measurements, the animals were allocated to a sham-injured group (n = 5), an injured and saline-treated group (n = 6), or an injured group treated with 4 mg of nebulized epinephrine every 4 hrs (n = 6). Inhalation injury was induced by 48 breaths of cotton smoke. The dose of epinephrine was derived from dose finding experiments (n = 7 sheep).

MEASUREMENTS AND MAIN RESULTS:

The injury induced significant increases in airway blood flows, bronchial wet/dry weight ratio, airway obstruction scores, ventilatory pressures, and lung malondialdehyde content, and contributed to severe pulmonary dysfunction as evidenced by a significant decline in Pao₂/Fio₂ ratio and increase in pulmonary shunt fraction. Nebulization of epinephrine significantly reduced tracheal and main bronchial blood flows, ventilatory pressures, and lung malondialdehyde content. The treatment was further associated with significant improvements of Pao₂/FIO₂ ratio and pulmonary shunting.

CONCLUSIONS:

Nebulization of epinephrine reduces airway blood flow and attenuates pulmonary dysfunction in sheep subjected to severe smoke inhalation injury. Future studies will have to improve the understanding of the underlying pathomechanisms and identify the optimal dosing for the treatment of patients with this injury.

• Authors: Matthias Lange, Atsumori Hamahata, Daniel L Traber, Robert A Cox, Gabriela A Kulp, Yoshimitsu Nakano, Lillian D Traber, David N Herndon, Perenlei Enkhbaatar
• Journal: Critical care medicine (Crit Care Med) Vol. 39 Issue 4 Pg. 718-24 (Apr 2011) ISSN: 1530-0293 [Electronic] United States
• PMID: 21263320 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epinephrine

Topics

• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epinephrine (administration & dosage, therapeutic use)
• Female
• Hemodynamics (drug effects)
• Hyperemia (drug therapy, etiology)
• Nebulizers and Vaporizers
• Pulmonary Circulation (drug effects)
• Pulmonary Edema (drug therapy, etiology)
• Pulmonary Gas Exchange (drug effects)
• Sheep
• Smoke Inhalation Injury (complications, drug therapy)