DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ANTITHROMBIN-III CONCENTRATES IN SEPTIC SHOCK WITH DISSEMINATED INTRAVASCULAR COAGULATION

Background: Septic shock is frequently complicated by a syndrome of di sseminated intravascular coagulation (DIC). Numerous uncontrolled clin ical studies have reported that antithrombin III (ATIII) substitution might prevent DIC and death in septic shock. Methods: We conducted a r andomized double-blind placebo-controlled trial in patients with a doc umented septic shock and DIC. The patients received either a placebo o r ATIII (90 to 120 IU/kg in loading dose, then 90 to 120 IU/kg/d durin g 4 days). Administration of fresh frozen plasma, platelets, and fibri nogen concentrates was restricted to patients with hemorrhages and sev ere decreases in prothrombin time, platelet count, and fibrinogen leve ls. Results: Thirty-give patients entered the study (18 placebo, 17 AT III). Both groups were well balanced for all demographic, hemodynamic, and biologic data. Three patients were excluded before the treatment allocation code was broken. In the ATIII group, ATIII levels were rapi dly corrected and remained over normal levels until day 10, sequential protein C and protein S levels were not modified. The duration of DIC was significantly reduced; in the ATIII group, 64 percent of patients were cured of DIC at day 2, and 71 percent were cured at the end of t reatment vs in the placebo group, 11 percent (p<0.01) and 33 percent ( p<0.05), respectively. In the 32 included patients, the mortality in I CU was reduced by 44 percent in the ATIII group (p=0.22, NS). Care loa ds and transfusion requirements were not different. No side effect was observed. Conclusions: Mortality was reduced by 44 percent in this tr ial, but the difference did not reach the statistical significance. Ci rculating protein C and protein S levels were not modified by ATIII su pplementation. High doses of ATIII concentrates significantly improved sepsis-induced DIC during septic shock. The trend toward improved sur vival suggests further randomized studies.