Treatment of sepsis with activated protein C

Encouraging news for well selected patients

See also Education and debate p 923

When uncomplicated sepsis progresses to uncontrolled systemic inflammation with evidence of organ dysfunction and impaired tissue perfusion (severe sepsis) or hypotension unresponsive to expansion of the circulating volume (septic shock), mortality is high (20%-60%).1^–3

Until now attempts to improve outcome by manipulating the inflammatory response have proved disappointing and in some instances possibly harmful.4 Failure to improve outcome with anti-inflammatory strategies can be explained partly by the limitations of the trials used to assess new treatments. These include the heterogeneity of patients in multicentre studies, the wide range in the severity of their illness, co-morbidity, standardised use of concomitant therapy (especially antibiotics), the timing of treatment, the question of attributable mortality, and the choice of outcome measures. The development of successful strategies to modulate inflammation has also been hampered by our limited understanding of the complex mechanisms that regulate the inflammatory response, combined with a naïve assumption that mortality can be reduced by temporarily neutralising just one component of the pro-inflammatory system.

But at last it seems that an effective treatment for some patients with severe sepsis has been identified in a recent …