PhD United States Army Institute of Surgical Research, Fort Sam Houston, Texas, USA, United States
Introduction/Rationale: Polytrauma is defined as two or more injuries that affect multiple organs systems. The systemic inflammatory responses after polytrauma, especially neutrophils mediated inflammation activation can lead to organ damage increasing morbidity and mortality. This study aimed to test whether the neutrophil elastase inhibitor sivelestat can reduce inflammation and improve outcomes in a rat polytrauma model.
Methods: Male Sprague Dawley rats anesthetized and given proper analgesics, were instrumented with catheters for blood pressure monitoring, hemorrhage, drug infusion, and sample collection. Rats were randomly assigned to either the injury control group (n = 9) or sivelestat (2 mg/kg, n = 10). All animals were subjected to a severe polytrauma consisting of soft tissue injury, fibula fracture, and pressure-controlled hemorrhage, followed by 30 minutes of blood resuscitation, and returned to cage and monitoring up to 72 hours or early death. The vital signs and blood samples were recorded and analyzed.
Results: Similar levels of blood loss were confirmed in both groups by hematocrits and hemoglobin. Sivelestat increased survival to 60% compared to the control of 33.3%. Treatment improved acute kidney injury parameters that include creatinine, Blood Urea Nitrogen and glomerular filtration rate. Also, sivelestat treatment corrected acidosis and increased blood pressure after injury.
Conclusion: The main findings indicate that sivelestat may decrease polytrauma induced organ failure in combat casualty care.
