Acute Respiratory Distress Syndrome Secondary to Inhalation of Chlorine Gas in Sheep

• Main Authors: Batchinsky, Andriy I, Martini, David K, Jordan, Bryan S, Dick, Edward J, Fudge, James, Baird, Candace A, Hardin, Denise E, Cancio, Leopoldo C
• Format: Report
• Language: English
• Subjects: ALVEOLI; Anatomy and Physiology; ANESTHESIA; ARDS(ACUTE RESPIRATORY DISTRESS SYNDROME); BLOOD CIRCULATION; CHLORINE; CI2(CHLORINE GAS); COMPUTERIZED TOMOGRAPHY; ETIOLOGY; EXPOSURE(PHYSIOLOGY); GASES; HISTOPATHOLOGY; INHALATION; LETHAL DOSAGE; LUNG; Medicine and Medical Research; MIGET(MULTIPLE INERT GAS ELIMINATION TECHNIQUE); PATHOPHYSIOLOGY; REGRESSION ANALYSIS; RESPIRATORY SYSTEM; RESPONSE(BIOLOGY); SHEEP; SIGNS AND SYMPTOMS; SMOKE; THERAPY; TICS(TOXIC INDUSTRIAL CHEMICALS); TOXICITY; Toxicology; TRAUMA; WOUNDS AND INJURIES

Toxic industrial chemicals (TICs) are potential terrorist weapons. Several TICs, such as chlorine, act primarily on the respiratory tract, but knowledge of the pathophysiology and treatment of these injuries is inadequate. This study aims to characterize the acute respiratory distress syndrome (ARDS) caused by chlorine gas (Cl2) inhalation in a large-animal model. Methods: Anesthetized female sheep were ventilated with 300 L of a Cl2 /air/ oxygen mixture for 30 minutes. In phase 1 (n 35), doses were 0 ppm (Group 1, n = 6); 120 ppm (Group 2, n = 6); 240 to 350 ppm (Group 3, n = 11); and 400 to 500 ppm (Group 4, n = 12). In phase 2 (n = 17), doses were 0 ppm (Group 5, n = 5); 60 ppm (Group 6, n = 5); and 90 ppm (Group 7, n = 7), and the multiple inert gas elimination technique (MIGET) was used to characterize the etiology of hypoxemia. Computed tomography (CT) scans were performed daily for all animals. Results: In Phase 1, lung function was well maintained in Group 1; Cl2 caused immediate and sustained acute lung injury (PaO2-to-FiO2 ratio, PFR less than 3.0) in Group 2 and ARDS (PFR less than 2.0) in Groups 3 and 4. All animals in Groups 1 and 2 survived 96 hours. Kaplan-Meier analysis showed dose- related differences in survival (log-rank test, p less than 0.0001). Logistic regression identified 280 ppm as the lethal dose 50%. CT and histopathology demonstrated lesions of both small airways and alveoli. In Phase 2, MIGET showed diversion of blood flow from normal to true-shunt lung compartments and, transiently, to poorly ventilated compartments. Conclusions: Cl 2 causes severe, dose-related lung injury, with features seen in both smoke inhalation and in ARDS secondary to systemic disease. This model will be used to test new therapeutic modalities. Published in the Journal of Trauma, Injury, Infection, and Critical Care, v60 p944-957, May 2006. Presented at the 64th Meeting of the American Association for the Surgery of Trauma, held in Atlanta, GA, 22-24 September 2005.