[Novel treatment for severe sepsis: recombinant human protein C (RHAPC)]

Abstract

Study design: Review of literature on novel therapy for severe sepsis within recombinant human protein C (rhAPC).

Data selection: MEDLINE and Polska Bibliografia Lekarska (2000-2003) were the main sources of the reviewed articles.

Data synthesis: Despite advances in critical care the rate of death from severe sepsis ranges from 30 to 50 percent (data related to patients with this complication treated in the intensive care units in the United States). In Poland about one third (27.3%) of all maternal deaths in 1991-2000 were from severe sepsis. Since the introduction of antibiotics, the first significant progress in effective therapy for severe sepsis was achieved due to the novel therapy within rhAPC. In 2001 Bernard et al. reported results of multi-center, placebo-controlled, randomized trial, in which the administration of rhAPC at 24 microgram/kg/h/96 hrs increased the survival in patients with severe sepsis by 6.1% (mortality rate was 24.7% for rhAPC group, while 30.8% for placebo group). There was an insignificant tendency for more bleeding in rhAPC patients (3.5% vs. 2.0% with placebo). In 2003 Dhainaut et al. described the pharmacological effects of rhAPC on severe sepsis. Fifteen biomarkers of inflammation or thrombosis/fibrinolysis were monitored. It was established that rhAPC decreases host response to infection resulting in lowering the levels of all inflammatory cytokines (TNFalfa, IL-1, IL-6 and IL-8), as well as lowering procoagulant markers, mainly D-dimers.

Conclusion: Sufficient data are available to approve rhAPC for treatment of patients with severe sepsis. Both anticoagulant and antiinflammatory properties of rhAPC, as well as profibrinolytic activity, are the rationale for the use of rhAPC.