Bilateral lower-extremity amputation wounds are associated with distinct local and systemic cytokine response

Background: Approximately 25% of U.S. military members sustaining extremity amputations in recent military conflicts have bilateral lower-extremity amputations (BLA). We investigated among combat-related extremity wounds whether BLA exhibit different bacterial burden, inflammatory response, and local complications. Methods: A total of 75 patients with combat-related extremity wounds (19 BLA) were evaluated for age, tobacco use, body mass index, Injury Severity Score, Acute Physiology and Chronic Health Evaluation II, and delayed primary closure time. Blood, wound exudates, and muscle biopsies were obtained and analyzed for cytokine and quantitative bacteriology, excluding patients using nonsteroidal anti-inflammatory medications and corticosteroids, due to potential effects on their inflammatory profile. Results: BLA was not associated with differences in age, tobacco use, body mass index, and delayed primary closure time, but these patients had increased Injury Severity Score, Acute Physiology and Chronic Health Evaluation II, and rates of critical colonization. Proinflammatory cytokines including tumor necrosis factor-α (exudate), interleukin (IL)-1 (exudate) and IL-6 (serum) were increased in BLA patients. They also had serum and exudate increased IL-8 and decreased IL-13 and granulocyte-macrophage colony-stimulating factor. Both wound dehiscence (WD) and heterotopic ossification (HO) were more common in BLA patients. Conclusion: BLA patients were more likely to exhibit critical bacterial colonization, a distinct inflammatory response, and develop WD and HO. Modulating this response represents an attractive target in an effort to prevent complications such as WD and HO.