Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation

OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized, controlled, experimental animal study. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40°C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. CONCLUSIONS: The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.