Evolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS)

In recent years, much basic science research has investigated the predisposing factors, initiation, propagation, and resolution of Gram-negative sepsis, endotoxaemic shock, and the newly defined entity of systemic inflammatory response syndrome (SIRS). A major cause of morbidity and mortality in the post-surgical, neonatal, and geriatric hospital population, sepsis has proven itself notoriously resistant to classical modes of therapy, including antibiotics, fluid/pressor and respiratory support. Recently, the widespread nosocomial isolation of new antibiotic-resistant strains of endotoxin-producing bacteria has further complicated management. For these reasons, there is much interest in alternative treatment modalities which focus upon the endotoxin molecule itself and the systemic inflammatory response it provokes via the cytokine, complement, and coagulation cascades. In this review, recent experimental approaches to the therapy of sepsis and SIRS are discussed in light of each step in the complex inflammatory cascade and in comparison to traditional approaches to prevention and therapy of Gram-negative bacteraemia and septic shock.