Low levels of protein C are associated with poor outcome in severe sepsis

Study objective: To investigate whether protein C levels predict 30-day mor tality rate, shock status, duration of ICU stay, and ventilator dependence in patients with sepsis. Design: Retrospective analysis of a subset of a previously published, prosp ective, randomized, double-blind, placebo-controlled trial ("Effects of Ibu profen on the Physiology and Survival of Patients With Sepsis" [ISS]). Setting: A multicenter study performed in the United States and Canada (sev en sites). Patients: Seventy hospitalized patients with acute severe sepsis and failure in one or more organs at entry info the ISS trial. Measurements and Main Results: Blood samples were obtained from all patient s at baseline and at 20, 44, 72, and 120 h after the initiation of study dr ug (ibuprofen or placebo) infusion. Data obtained at these times included p latelet count, prothrombin time, and partial thromboplastin time. The resul ts described in this article are based on a subset of the total ISS populat ion for whom additional coagulation assays were performed on the blood samp les obtained at baseline and 44 h. These assays included protein C antigen, D-dieter, and fibrinogen levels. A total of 63 of the 70 patients (90%) st udied in this report had acquired protein C deficiency at entry to the ISS trial (baseline). The presence and severity of acquired protein C deficienc y were associated with poor clinical outcome, including lower survival rate , higher incidence of shock, and fewer ICU-free and ventilator-free days. Conclusions: Acquired protein C deficiency may be useful in predicting clin ical outcome in patients with sepsis. Clinical studies are warranted to det ermine whether the replacement of protein C in sepsis patients may improve outcome.