Pathophysiology and treatment of chlorine gas-induced lung injury: an experimental study in pigs
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
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.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 877
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-24066Local ID: 3625ISBN: 91-7373-853-0OAI: oai:DiVA.org:liu-24066DiVA: diva2:244382
2004-12-20, Aulan, Katastrofmedicinskt Centrum, Hälsouniversitetet, Linköping, 13:00 (Swedish)
Knudsen, Kai, Docent
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