CURRENT PROSPECTS FOR THE TREATMENT OF CLINICAL SEPSIS

Objectives: To review the role of antimediator therapy in the inflammatory cascade associated with sepsis, and to review the status of animal and clinical studies being conducted on novel therapies for septic shock. Data Sources: Information presented at the 22nd Educational and Scientific Meeting of the Society of Critical Care Medicine on June 9-13, 1993 in New York City was reviewed, along with supportive documentation from the English language literature. Study Selection: Controlled animal studies that provide evidence for the effectiveness of antiendotoxin and anticytokine therapies. The preliminary results of selected clinical trials are also presented. Data Extraction: This review focuses on data describing the potential role of mediator antagonists in the treatment of septic shock. Data Synthesis: Information concerning the effectiveness and tolerability of these therapies has been integrated into a description of emerging therapies for septic shock. Conclusions: Clinical trials of antiendotoxin antibodies have not shown them to have therapeutic benefit. New agents that neutralize or antagonize the cellular effects of endotoxin may provide an alternative means to inhibit endotoxin effects during severe Gram-negative infections. Anti-interleukin-1 and antitumor necrosis factor-alpha therapies have demonstrated efficacy in animal models, but the results have been inconsistent in human trials. Preliminary results from clinical trials of cytokine antagonists suggest that these therapies may be effective in the most severely ill patients. Further clinical trials will be required to determine the therapeutic role of these agents in septic shock.