Septic shock: new pharmacotherapy options or better trial design?

Over the last two decades, many of the mechanisms underlying the pathophysiology of sepsis have been uncovered, but this has not led to the development of effective therapies for sepsis. Despite improvements in the general care of critically ill patients in recent years, mortality rates for patients with severe sepsis and septic shock remain high at 30 to 50% and there is an urgent need to develop new, effective therapeutic strategies.

Attempts to develop a therapy for sepsis have focused on modulating this immune response. Past and present clinical research in this field are reviewed and promising candidates and approaches for the future are discussed.

Many reasons have been put forward over the years to explain the many negative results from trials of immunomodulatory therapies. Future studies need to be designed to specifically target patients who can benefit from the intervention being studied rather than at the sepsis population in general. The timing of administration of potential therapies also needs to be taken more into consideration.