Background: Over the past 30 years, efforts have been made to identify therapeutic targets in the host response to infection.
Methods: A review of the randomized controlled clinical sepsis trials and meta-analyses of glucocorticoids, mediator-specific anti-inflammatory agents, and anticoagulant agents was performed.
Results: The effects of glucocorticoids in sepsis appear to be dose-dependent, with high doses decreasing survival and low doses improving survival. As a class, the mediator-specific anti-inflammatory agents have a small beneficial effect on survival; however, no single agent has demonstrated significant benefit. The treatment effects of these agents appear to be related to the patient’s risk of death. As a class, the anticoagulant agents do not improve survival; however, the efficacy of these agents may have been confounded by concurrent heparin therapy. Activated protein C demonstrated a beneficial effect on survival that was dependent on severity of illness.
Conclusion: Trials of agents directed at altering the host’s response during sepsis have had variable results, and it appears that several different factors may alter the efficacy of these agents.
From the Critical Care Medicine Department, Clinical Center, National Institutes of Health (K.J.D., M.H., C.N., P.Q.E., P.C.M.), Bethesda, Maryland, and Department of Surgery, Massachusetts General Hospital (K.J.D., P.C.M.), Boston, Massachusetts.
Submitted for publication May 13, 2004.
Accepted for publication January 13, 2005.
Address for reprints: Peter C. Minneci, MD, Critical Care Medicine Department, National Institutes of Health, Building 10, Room 7D43, 10 Center Drive, MSC 1662, Bethesda, MD 20892; email: email@example.com.