Adjunctive therapy of severe sepsis and septic shock in adults

Sepsis continues to be a major unresolved medical challenge of the present. Despite earlier diagnosis and treatment initiation, source control, improvements in the standard of care and attempts at standardization of treatment and resuscitation protocols intensive care unit mortality rates for severe sepsis is 32.2% and 54.1% for septic shock. Further reduction in mortality may be achievable through knowledge and use of the expanding field of adjunctive therapy: a supplement to optimal, supportive, intensive therapy and antibiotic treatment.

Numerous and unsuccessful trials targeted at inhibiting various essential inflammatory mediators and receptors involved in the sepsis syndrome have failed to show a reduction in mortality, raising the question whether mortality in sepsis actually derives from an uncontrolled pro-inflammatory response. Thus, more broad based attempts at modulating the inflammatory response to infection like corticosteroids and drotrecogin alfa (activated) are to date the only drugs to have demonstrated mortality benefits in large randomized controlled trials. Advances in understanding the pathophysiology of sepsis as a heterogeneous, dynamic syndrome caused by imbalances in the inflammatory network have provided newer hemofiltration techniques with a strong treatment rationale. Furthermore, endotoxin adsorption, if effective, has the potential to prevent further progression of the biological cascade of gram-negative sepsis.