Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep

Collette Jonkam, Yong Zhu, Sam Jacob, Sebastian Rehberg, Edward Kraft, Atsumori Hamahata, Yoshimitsu Nakano, Lillian D. Traber, David Herndon, Daniel L. Traber, Hal K. Hawkins, Perenlei Enkhbaatar, Robert A. Cox

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objectives: Inhalation injury contributes to the morbidity and mortality of burn victims. In humans and in an ovine model of combined smoke inhalation and burn injury, bronchospasm and acute airway obstruction contribute to progressive pulmonary insufficiency. This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide, an M1 and M3 muscarinic receptor antagonist, will decrease the airway constrictive response and acute bronchial obstruction to improve pulmonary function compared to injured animals without treatment. Design: Randomized, prospective study involving 32 sheep. Setting: Large-animal intensive care research laboratory. Interventions: The study consisted of six groups: a sham group (n = 4, instrumented noninjured), a control group (n = 6, injured and not treated), and tiotropium bromide-treated groups, including both preinjury and postinjury nebulization protocols. Treatments for these groups included nebulization with 36 μg of tiotropium bromide 1 hr before injury (n = 6) and postinjury nebulization protocols of 18 μg (n = 6), 36 μg (n = 6), and 72 μg (n = 4) administered 1 hr after injury. All treated groups received an additional 14.4 μg every 4 hrs for the 24-hr study period. Main results: Pretreatment with tiotropium bromide significantly attenuated the increases in ventilatory pressures, pulmonary dysfunction, and upper airway obstruction that occur after combined smoke inhalation and burn injury. Postinjury treatments with tiotropium bromide were as effective as pretreatment in preventing pulmonary insufficiency, although a trend toward decreased obstruction was present only in all post-treatment conditions. There was no improvement noted in pulmonary function in animals that received a higher dose of tiotropium bromide. Conclusions: This study describes a contribution of acetylcholine to the airway constrictive and lumenal obstructive response after inhalation injury and identifies low-dose nebulization of tiotropium bromide as a potentially efficacious therapy for burn patients with severe inhalation injury.

Original languageEnglish (US)
Pages (from-to)2339-2344
Number of pages6
JournalCritical Care Medicine
Volume38
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Smoke Inhalation Injury
Muscarinic Antagonists
Muscarinic Receptors
Sheep
Lung
Inhalation Burns
Inhalation
Wounds and Injuries
Airway Obstruction
Therapeutics
Bronchial Spasm
Critical Care
Tiotropium Bromide
Acetylcholine
Prospective Studies
Morbidity
Pressure
Control Groups
Mortality

Keywords

  • acute lung injury
  • airway
  • alveolar injury
  • constriction
  • edema
  • sheep
  • smoke inhalation
  • tiotropium bromide

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep. / Jonkam, Collette; Zhu, Yong; Jacob, Sam; Rehberg, Sebastian; Kraft, Edward; Hamahata, Atsumori; Nakano, Yoshimitsu; Traber, Lillian D.; Herndon, David; Traber, Daniel L.; Hawkins, Hal K.; Enkhbaatar, Perenlei; Cox, Robert A.

In: Critical Care Medicine, Vol. 38, No. 12, 12.2010, p. 2339-2344.

Research output: Contribution to journalArticle

Jonkam, C, Zhu, Y, Jacob, S, Rehberg, S, Kraft, E, Hamahata, A, Nakano, Y, Traber, LD, Herndon, D, Traber, DL, Hawkins, HK, Enkhbaatar, P & Cox, RA 2010, 'Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep', Critical Care Medicine, vol. 38, no. 12, pp. 2339-2344. https://doi.org/10.1097/CCM.0b013e3181f8557b
Jonkam, Collette ; Zhu, Yong ; Jacob, Sam ; Rehberg, Sebastian ; Kraft, Edward ; Hamahata, Atsumori ; Nakano, Yoshimitsu ; Traber, Lillian D. ; Herndon, David ; Traber, Daniel L. ; Hawkins, Hal K. ; Enkhbaatar, Perenlei ; Cox, Robert A. / Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep. In: Critical Care Medicine. 2010 ; Vol. 38, No. 12. pp. 2339-2344.
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abstract = "Objectives: Inhalation injury contributes to the morbidity and mortality of burn victims. In humans and in an ovine model of combined smoke inhalation and burn injury, bronchospasm and acute airway obstruction contribute to progressive pulmonary insufficiency. This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide, an M1 and M3 muscarinic receptor antagonist, will decrease the airway constrictive response and acute bronchial obstruction to improve pulmonary function compared to injured animals without treatment. Design: Randomized, prospective study involving 32 sheep. Setting: Large-animal intensive care research laboratory. Interventions: The study consisted of six groups: a sham group (n = 4, instrumented noninjured), a control group (n = 6, injured and not treated), and tiotropium bromide-treated groups, including both preinjury and postinjury nebulization protocols. Treatments for these groups included nebulization with 36 μg of tiotropium bromide 1 hr before injury (n = 6) and postinjury nebulization protocols of 18 μg (n = 6), 36 μg (n = 6), and 72 μg (n = 4) administered 1 hr after injury. All treated groups received an additional 14.4 μg every 4 hrs for the 24-hr study period. Main results: Pretreatment with tiotropium bromide significantly attenuated the increases in ventilatory pressures, pulmonary dysfunction, and upper airway obstruction that occur after combined smoke inhalation and burn injury. Postinjury treatments with tiotropium bromide were as effective as pretreatment in preventing pulmonary insufficiency, although a trend toward decreased obstruction was present only in all post-treatment conditions. There was no improvement noted in pulmonary function in animals that received a higher dose of tiotropium bromide. Conclusions: This study describes a contribution of acetylcholine to the airway constrictive and lumenal obstructive response after inhalation injury and identifies low-dose nebulization of tiotropium bromide as a potentially efficacious therapy for burn patients with severe inhalation injury.",
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AB - Objectives: Inhalation injury contributes to the morbidity and mortality of burn victims. In humans and in an ovine model of combined smoke inhalation and burn injury, bronchospasm and acute airway obstruction contribute to progressive pulmonary insufficiency. This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide, an M1 and M3 muscarinic receptor antagonist, will decrease the airway constrictive response and acute bronchial obstruction to improve pulmonary function compared to injured animals without treatment. Design: Randomized, prospective study involving 32 sheep. Setting: Large-animal intensive care research laboratory. Interventions: The study consisted of six groups: a sham group (n = 4, instrumented noninjured), a control group (n = 6, injured and not treated), and tiotropium bromide-treated groups, including both preinjury and postinjury nebulization protocols. Treatments for these groups included nebulization with 36 μg of tiotropium bromide 1 hr before injury (n = 6) and postinjury nebulization protocols of 18 μg (n = 6), 36 μg (n = 6), and 72 μg (n = 4) administered 1 hr after injury. All treated groups received an additional 14.4 μg every 4 hrs for the 24-hr study period. Main results: Pretreatment with tiotropium bromide significantly attenuated the increases in ventilatory pressures, pulmonary dysfunction, and upper airway obstruction that occur after combined smoke inhalation and burn injury. Postinjury treatments with tiotropium bromide were as effective as pretreatment in preventing pulmonary insufficiency, although a trend toward decreased obstruction was present only in all post-treatment conditions. There was no improvement noted in pulmonary function in animals that received a higher dose of tiotropium bromide. Conclusions: This study describes a contribution of acetylcholine to the airway constrictive and lumenal obstructive response after inhalation injury and identifies low-dose nebulization of tiotropium bromide as a potentially efficacious therapy for burn patients with severe inhalation injury.

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KW - airway

KW - alveolar injury

KW - constriction

KW - edema

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KW - smoke inhalation

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