EVOLVING STRATEGIES IN THE TREATMENT OF SEPSIS AND SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS)

In recent years, much basic science research has investigated the pred isposing factors, initiation, propagation, and resolution of Cram-nega tive sepsis, endotoxaemic shock, and the newly defined entity of syste mic inflammatory response syndrome (SIRS). A major cause of morbidity and mortality in the post-surgical, neonatal, and geriatric hospital p opulation, sepsis has proven itself notoriously resistant to classical modes of therapy, including antibiotics, fluid/pressor and respirator y support. Recently, the widespread nosocomial isolation of new antibi otic-resistant strains of endotoxin-producing bacteria has further com plicated management. For these reasons, there is much interest in alte rnative treatment modalities which focus upon the endotoxin molecule i tself and the systemic inflammatory response it provokes via the cytok ine, complement, and coagulation cascades. In this review, recent expe rimental approaches to the therapy of sepsis and SIRS are discussed in light of each step in the complex inflammatory cascade and in compari son to traditional approaches to prevention and therapy of Gram-negati ve bacteraemia and septic shock.