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Inhaled budesonide in experimental chlorine gas lung injury: influence of time interval between injury and treatment
Linköping University, Department of Biomedicine and Surgery, Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
Linköping University, Faculty of Health Sciences.
2002 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 28, no 3, 352-357 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To examine the time window between injury and treatment during which nebulized corticosteroid lessens lung injury induced by chlorine gas inhalation.

Design: An experimental laboratory study.

Setting: Academic research laboratory.

Subjects: Twenty-four juvenile female pigs.

Interventions: Twenty-four mechanically ventilated pigs were exposed to chlorine gas (400 PPM in air) for 20 min, then divided into four groups (six in each group). Nebulized budesonide (BUD) was given immediately (BUD 0 min), 30 min (BUD 30 min) or 60 min (BUD 60 min) after chlorine gas exposure. Six pigs receiving nebulized saline served as controls.

Measurements and main results: Hemodynamics, gas exchange and lung mechanics were evaluated for 5 h after chlorine gas exposure. All animals had an immediate increase in airway and pulmonary artery pressure and a sharp drop of arterial oxygenation. The mean arterial oxygen tension of BUD 0 min and BUD 30 min animals was significantly higher than in the control and the BUD 60 min groups (p<0.001). The recovery of lung compliance in the BUD 0 min and the BUD 30 min groups was significantly more rapid than in the control and the BUD 60 min groups (p<0.001). The pulmonary wet to dry weight ratio was greater in the control group than in the BUD-treated groups (p<0.05).

Conclusion: Treatment with inhaled budesonide immediately or 30 min after chlorine gas lung injury had similar positive effects on symptoms and signs of pulmonary injury, whereas treatment delayed for 60 min was less effective.

Place, publisher, year, edition, pages
2002. Vol. 28, no 3, 352-357 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25446DOI: 10.1007/s00134-001-1175-4Local ID: 9892OAI: oai:DiVA.org:liu-25446DiVA: diva2:245775
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Pathophysiology and treatment of chlorine gas-induced lung injury: an experimental study in pigs
Open this publication in new window or tab >>Pathophysiology and treatment of chlorine gas-induced lung injury: an experimental study in pigs
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One of the most threatening scenarios in disaster medicine is the accidental release of toxic gases with the exposure of many people. In this respect, chlorine gas remains a significant threat due to its abundant use and transport through densely populated areas in modem society. Access to a simple and effective method of treatment that could be started early would be of great value. The main purpose of this study was to test a series of hypotheses related to chlorine gas lung injury and its treatment.

Anesthetized and mechanically ventilated pigs were exposed to chlorine gas (400 parts per million in air) using a closed system with a ventilator connected to gas cylinders. Plasma endothelin-1 (ET -1) and pro inflammatory cytokines were evaluated for 5 hours after injury while hemodynamics, gas exchange and lung mechanics were followed for 23 hours. Histopathology and lung water balance were assessed at the end of the experiment.

Chlorine gas exposure induced a rise in circulating ET-1 and circulating cytokines (TNF-α, and IL-1ß, IL-6). Pretreatment or treatment with tezosentan, a potent dual endothelin receptor antagonist, reduced the deterioration of pulmonary function induced by chlorine gas inhalation. Immediate prone positioning after chlorine gas injury not only inhibited deterioration of gas exchange but was also associated with improved pulmonary function and oxygen transport. Nebulized budesonide given within 30 minutes after chlorine gas lung injury was effective in preventing further progression of lung dysfunction but the effect of treatment given beyond 60 minutes was less efficient. The positive effects on pulmonary function and lung water were similar whether corticosteroids were given by aerosol or intravenously. Combined treatment with nebulized terbutaline and budesonide was associated with better recovery of lung function than either drug alone.

In conclusion, these studies outline the early pathophysiology of chlorine gas injury. They show that the endothelin system mediates the early pulmonary hypertensive and also to some extent the brochoconstrictive responses to inhaled chlorine gas. The work supports early administration of corticosteroids and ß2-agonists for individuals that are exposure to chlorine gas. In addition, early prone positioning of patients with severe chlorine gas lung injury may be useful.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2004. 53 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 877
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24066 (URN)3625 (Local ID)91-7373-853-0 (ISBN)3625 (Archive number)3625 (OAI)
Public defence
2004-12-20, Aulan, Katastrofmedicinskt Centrum, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-26Bibliographically approved

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Wang, JianpuWalther, Sten

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