A novel animal model of sepsis after acute lung injury in sheep

Objective: Patients with acute lung injury after smoke inhalation often develop pneumonia subsequently complicated by sepsis. This often is a fatal complication. The aim of this study was' to develop a standardized and reproducible model of hyperdynamic sepsis after smoke inhalation in sheep. Design: Prospective, experimental study in sheep. Settings: Experimental laboratory in a university hospital. Subjects: Twenty-one female Merino ewes. Intervention: Animals were anesthetized and surgically pre.. pared for this chronic study. After a week of recovery, baseline data were collected. After tracheostomy was performed, sheep were connected to a volume-controlled ventilator. Acute lung injury was produced by insufflating the lungs with 48 breaths of cotton smoke. During halothane anesthesia, live Pseudomonas aeruginosa bacteria suspended in a 30-mL. saline solution con.. taining 2-5 x 10(11) colony-forming units were instilled through El bronchoscope into the right lower and middle lung lobes (10 mL. each) and left lower lung lobe (10 mL; n = 10). Eleven sheep were given smoke but not bacteria. After injury and the bacterial challenge, the animals were ventilated mechanically with 100% oxygen. The animals were monitored for 48 hrs. A aeruginosa was detected in blood cultures after 14-48 hrs. Measurements and Main Results: The sheep developed a hyperkinetic cardiovascular response concomitant with a decrease in Pa0(2) similar to severe sepsis in human patients who meet the criteria, for acute respiratory distress syndrome (Pa0(2)/FI0(2) <200). These changes were more severe than in animals exposed to smoke inhalation alone. Mean arterial pressures at 48 hrs in the smoke-alone and the smoke + sepsis group were 85.5 +/- 5.2 and 68.1 +/- 7.6 mm Hg, respectively (mean +/- SE, P <.05). Conclusion: This animal model closely resembles hyperdynamic sepsis in humans and may be of great value for studies of sepsis with smoke inhalation.