Activated protein C is an endogenous modulator with antithrombotic, anti-inflammatory and profibrinolytic properties. Underexpression of activated protein C plays a role in the progression of sepsis. Drotrecogin (Xigris®) is recombinate

One Two Three Four Number of Dysfunctional Organs

Figure 7.1. Mortality is directly associated with the number organ failures.

activated protein C that reduces inflammation, coagulation and increased fibrinolysis. The PROWESS trial evaluated the use of drotrecogin alfa in severe sepsis and found an improved survival at 28 days. Mortality was 24.7% in drotrecogin alfa treatment groups versus 30.8% in control groups. Patients at the highest rick (APACHE > 25) had the greatest benefit with a 13% reduction in mortality. Those patients with APACHE < 20 had the lease benefit. Bleeding complications with the use of drotrecogin alfa are 17% versus 8% in placebo groups.

Current dosing for Xigris is 24 ^g/kg/hour over 4 days. In a recent symposium, patients with significant improvement the infusion was stopped early without any significant loss of benefit. This drug is expensive with a cost of infusion at $6600.00. The end result is 18 patients must be treated to save one life with Xigris.

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