Chapterr 8 Treatmentt with recombinant human activated proteinn C obviates additional anticoagulation duringg continuous venovenous hemofiltration in patientss with severe sepsis

t Background d Recombinantt human activated protein C (rhAPC) is the first drug for which a reduction of mortalityy in severe sepsis has been demonstrated. In expectance of registration, more informationn regarding efficacy and safety was gathered in the ENHANCE study. Several patientss participating in this study needed renal replacement therapy. Aim of this studyy was to evaluate whether continuous venovenous hemofiltration can be performed withoutt the addition of another anticoagulant in patients treated with rhAPC. Methodss and Results Threee severely septic patients with acute renal failure were treated with rhAPC and hemofiltration.. Within 48 h after the onset of organ failure, rhAPC was administered intravenouslyy at a constant rate of 24 ug/kg/h for a total of 96 h. Predilutional hemofiltrationn with a blood flow rate of 150 ml/min and an ultrafiltrate rate of 20000 ml/h was performed using a cellulose triacetate membrane. After termination of thee treatment with rhAPC, hemofiltration was performed using unfractionated heparin (UFH)) as an anticoagulant. The hemofiltration runs during rhAPC were compared with thosee during UFH, each patient being his own control. Mean filter survival time during rhAPCC was 55 13 h compared with 66 19 h for those during UFH (p=0.62). Filter survivall time in both groups was limited by filter pore obstruction. Conclusions s Inn these three severely septic patients treated with rhAPC and hemofiltration, circuit survivall times during rhAPC and UFH were similar. This preliminary finding suggests that whenn rhAPC is administered, no additional anticoagulant therapy may be needed to preventt thrombosis in the extracorporeal circuit.