10 Feb 06
Recombinant activated protein C: Decisions for administration
By RP Dellinger
Critical Care Medicine 34(2): 530-531
“There are two tragedies in life. One is not to get your heart’s desire. The other is to get it.” – George Bernard Shaw
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So where do we stand? In my opinion we stand right where the FDA recommends, that is, administering rhAPC in situations of high risk of death, while considering counterbalancing effects of risk for life-threatening hemorrhage. When you have high risk of death from severe sepsis, then it is worth giving an expensive drug with a significant side effect profile, when that drug has satisfied the a priori end point for beneficial effect in a single large randomized placebo-controlled clinical trial. What is high risk of death? I believe that in general, high risk of death remains the four considerations as recommended by the Surviving Sepsis Campaign guidelines: acute respiratory distress syndrome, septic shock, multiple organ failure, and APACHE II ≥25. One caveat is that the ADDRESS trial results would suggest that an APACHE II ≥25 in and of itself may not represent high risk of death.