Activated protein C for severe sepsis: what's the current status?

Activated protein C (Xigris) is given a soft recommendation for use in patients with severe sepsis at high risk of death in the latest version of the Surviving Sepsis guidelines.


In recent years it has fallen out of use due to various controversies, including allegations of undue Pharma influence, concern about bleeding risk and mixed evidence since the publication of PROWESS concerning optimal patient selection.


So what is its current status?


Two recent articles caught my attention, which I haven't blogged before. This large propensity matched retrospective cohort study showed a mortality benefit almost identical to that observed in PROWESS. This updated Cochrane review, on the other hand, found no evidence of benefit.


So for now the drug remains controversial. We'll have to wait for the results of Prowess-SHOCK, in which it is studied in the sickest of patients, to get better answers.


Meanwhile in a recent podcast at the EM Crit blog sepsis expert Emanuel Rivers, the originator of early goal directed therapy (EGDT) was asked about the controversy. He cited the increasing evidence that use of Xigris is time dependent, and blames some of the negative results on giving the drug inappropriately late, remarking that inappropriately late use in the course of sepsis has unfortunately “done this drug in.”