Development and Evaluation of New Products for the Far-Forward Care of Combat Casualties With Acute Lung Injury
Abstract
To characterize the acute respiratory distress syndrome (ARDS) caused by chlorine gas (Cl2). Toxic industrial chemicals (TICs) have recently been identified as potential terrorist weapons. Several TICs act primarily on the respiratory tract, but more work is needed to define the pathophysiology and treatment of these injuries. Anesthetized female sheep (n=35, 42.4kg +/- 5.4 SD) were ventilated with 300 L of a Cl2/air/oxygen mixture over 30 min. Doses were: 0 ppm (Control, Group 1); 120 ppm (Low Dose, Group 2); 240-350 ppm (Medium, Group 3); and 400-500 ppm (High, Group 4). After injury they were maintained for 96 h in an animal ICU. Gentle mechanical ventilation (peak airway pressure < 40 cmH2O) was required to limit barotrauma. Cardiopulmonary data were collected every 6 h, and CT scans daily. The multiple inert gas elimination technique (MIGET) was used to characterize the etiology of hypoxemia. Lung function was well maintained in Group 1; Cl2 caused immediate and sustained acute lung injury (PaO2-to-FiO2 ratio, PFR<300) in Group 2, and ARDS (PFR<200) in Groups 3-4 (ANOVA p<.0001 between/within groups). Cl2 also rapidly caused hypotension and decreased cardiac output, lasting 48 h in survivors. All animals in Groups 1-2 survived 96 h. Kaplan-Meier analysis showed dose-related differences in survival (Log Rank test, p<.OO0l). Logistic regression identified 280 ppm as the lethal dose 50%. CT and histopathology demonstrated lesions of both small airways and alveoli. MIGET showed diversion of blood flow from normal to true-shunt lung segments. Cl2 causes severe, dose-related lung injury, with features seen in both smoke inhalation (small airway lesions) and ARDS secondary to systemic disease (alveolar-endothelial lesions). This model will be used to test the Intravenous Membrane Oxygenator being developed by ALung Technologies, Inc. in collaboration with the University of Pittsburgh.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA443894
Entities
People
- Leopoldo C. Cancio