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

Matthias Lange, Atsumori Hamahata, Daniel L. Traber, Robert A. Cox, Gabriela A. Kulp, Yoshimitsu Nakano, Lillian D. Traber, David Herndon, Perenlei Enkhbaatar

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)718-724
Number of pages7
JournalCritical Care Medicine
Volume39
Issue number4
DOIs
StatePublished - Apr 2011

Fingerprint

Smoke Inhalation Injury
Hyperemia
Epinephrine
Lung
Inhalation
Sheep
Acute Lung Injury
Wounds and Injuries
Malondialdehyde
Smoke
Pressure
Airway Obstruction
Edema
Randomized Controlled Trials
Animal Models
Morbidity
Weights and Measures
Mortality

Keywords

  • acute lung injury
  • adrenaline
  • aerosolization
  • airway blood flow
  • bronchodilatation
  • sheep

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Preclinical evaluation of epinephrine nebulization to reduce airway hyperemia and improve oxygenation after smoke inhalation injury. / Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L.; Cox, Robert A.; Kulp, Gabriela A.; Nakano, Yoshimitsu; Traber, Lillian D.; Herndon, David; Enkhbaatar, Perenlei.

In: Critical Care Medicine, Vol. 39, No. 4, 04.2011, p. 718-724.

Research output: Contribution to journalArticle

Lange, Matthias ; Hamahata, Atsumori ; Traber, Daniel L. ; Cox, Robert A. ; Kulp, Gabriela A. ; Nakano, Yoshimitsu ; Traber, Lillian D. ; Herndon, David ; Enkhbaatar, Perenlei. / Preclinical evaluation of epinephrine nebulization to reduce airway hyperemia and improve oxygenation after smoke inhalation injury. In: Critical Care Medicine. 2011 ; Vol. 39, No. 4. pp. 718-724.
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AU - Cox, Robert A.

AU - Kulp, Gabriela A.

AU - Nakano, Yoshimitsu

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AB - 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.

KW - acute lung injury

KW - adrenaline

KW - aerosolization

KW - airway blood flow

KW - bronchodilatation

KW - sheep

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