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

Ernesto Lopez, Osamu Fujiwara, Francisco Lima-Lopez, Oscar Suman, Ronald P. Mlcak, Hal K. Hawkins, Robert A. Cox, David Herndon, Donald Prough, Perenlei Enkhbaatar

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 (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.

Original languageEnglish (US)
Pages (from-to)e89-e96
JournalCritical Care Medicine
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Smoke Inhalation Injury
Epinephrine
Blood Vessels
Sheep
Lung
Water
Proteins
Adrenergic Receptors
Anesthesia and Analgesia
Therapeutics
Body Surface Area
Hyperemia
Wounds and Injuries
Body Fluids
Mechanical Ventilators
Burns
Smoke
Respiratory System
Inhalation
Compliance

Keywords

  • Acute respiratory distress syndrome
  • Airway hyperemia
  • Burn and smoke inhalation
  • Epinephrine
  • Vascular permeability

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine with Burn and Smoke Inhalation Injury. / Lopez, Ernesto; Fujiwara, Osamu; Lima-Lopez, Francisco; Suman, Oscar; Mlcak, Ronald P.; Hawkins, Hal K.; Cox, Robert A.; Herndon, David; Prough, Donald; Enkhbaatar, Perenlei.

In: Critical Care Medicine, Vol. 44, No. 2, 01.02.2016, p. e89-e96.

Research output: Contribution to journalArticle

Lopez, Ernesto ; Fujiwara, Osamu ; Lima-Lopez, Francisco ; Suman, Oscar ; Mlcak, Ronald P. ; Hawkins, Hal K. ; Cox, Robert A. ; Herndon, David ; Prough, Donald ; Enkhbaatar, Perenlei. / Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine with Burn and Smoke Inhalation Injury. In: Critical Care Medicine. 2016 ; Vol. 44, No. 2. pp. e89-e96.
@article{bf3a4b5dd43c44ca8724c003716b0b70,
title = "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 (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.",
keywords = "Acute respiratory distress syndrome, Airway hyperemia, Burn and smoke inhalation, Epinephrine, Vascular permeability",
author = "Ernesto Lopez and Osamu Fujiwara and Francisco Lima-Lopez and Oscar Suman and Mlcak, {Ronald P.} and Hawkins, {Hal K.} and Cox, {Robert A.} and David Herndon and Donald Prough and Perenlei Enkhbaatar",
year = "2016",
month = "2",
day = "1",
doi = "10.1097/CCM.0000000000001349",
language = "English (US)",
volume = "44",
pages = "e89--e96",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine with Burn and Smoke Inhalation Injury

AU - Lopez, Ernesto

AU - Fujiwara, Osamu

AU - Lima-Lopez, Francisco

AU - Suman, Oscar

AU - Mlcak, Ronald P.

AU - Hawkins, Hal K.

AU - Cox, Robert A.

AU - Herndon, David

AU - Prough, Donald

AU - Enkhbaatar, Perenlei

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - Acute respiratory distress syndrome

KW - Airway hyperemia

KW - Burn and smoke inhalation

KW - Epinephrine

KW - Vascular permeability

UR - http://www.scopus.com/inward/record.url?scp=84954392299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954392299&partnerID=8YFLogxK

U2 - 10.1097/CCM.0000000000001349

DO - 10.1097/CCM.0000000000001349

M3 - Article

C2 - 26465218

AN - SCOPUS:84954392299

VL - 44

SP - e89-e96

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 2

ER -