Objective: Treatment with recombinant human activated protein C (APC) decreases mortality in patients with severe sepsis, mainly by faster resolving cardiorespiratory failure. Whether the concomitant presence of sepsis-induced acute kidney injury (AKI) could alter this beneficial effect, remains speculative. We investigated whether APC influenced outcome and evolution of sepsis-induced cardiorespiratory failure complicated by AKI.
Design: Open-label, randomized, controlled study.
Setting: 24-bed medical-surgical intensive care unit.
Patients: Patients with bilateral pneumonia-induced septic shock were enrolled and divided in two groups according to the presence (group A) or absence (group B) of AKI. Only patients with AKI, classified as “failure” according to the RIFLE criteria were included.
Interventions: All patients were adequately fluid-resuscitated, mechanically ventilated, and received norepinephrine treatment. APC was given as a continuous infusion of 24 µg/kg/h for 4 days. Continuous venovenous hemofiltration at a rate of 35 ml/kg/h was started upfront in all patients of group A.
Measurements and results: 32 patients were available for analysis (group A; n=17 and group B; n=15). Oxygenation, vasopressor requirement, and renal outcome were evaluated daily during APC infusion. Catecholamine need could be lowered significantly in both groups but the decrease was more rapid and pronounced in group A. Oxygenation improved markedly in both groups. ICU mortality remained high and comparable between groups. All patients who remained oligo-anuric during APC treatment died.
Conclusions: We confirmed the previously reported beneficial effects of APC on respiratory and cardiovascular dysfunction in septic shock. ICU mortality was high but unaffected by concomitant AKI. Persistent oligo-anuria during APC infusion was associated with a poor prognosis.