Use of drotrecogin alpha in a surgical septic cohort of patients

Abstract number: P1452

Mas-Serrano P., Navarro-Martinez J., Aparicio Cueva M., Ordovas Baines J.P., Company Teuler R.

Objectives: Drotrecogin alpha is a drug used in high risk patients with severe sepsis and septic shock, defined by an Acute Physiology and Chronic Health Evaluation (APACHE II) score in the United States indication more than 25 and at least 2 acute organ dysfunctions in the European Union indication (SOFA). Drotrecogin alpha is considered to have a broad range of effects, not only on multiple stages of the coagulation cascade, but also as a fibrinolytic agent and as an anti-inflammatory agent. The main side effect is the risk of bleeding due to the inactivation of the V and VIII coagulation factors. In both clinical trials and "real practice" registries the proportion of surgical patients is always small. After surgery there is a 12 hour window for the initiation of the therapy with drotrecogin alpha, even though the risk of bleeding continues during all the treatment.

Methods: We analyzed retrospectively all the patients (78) admitted to the Surgical Critical Care Unit with surgery in the previous 30 days and that were treated with drotrecogin alpha between June 2003 and November 2008.

Results: We included 78 patients. The age was 62.41±16.9 (69.2% male). The severity score measured by the APACHE II was 20.2±5.0 and the SOFA was 3.3±1.0 (98.7% had 2 or more organ dysfunction). The delay from the diagnosis of the sepsis until the initiation of the therapy was 22.4±16.5 hours. The origin of the patient was in the 51.3% nosocomial, and the surgery was emergency in the 88.5% of the cases. The type of surgery was in the 74.4% abdominal, 5.1% cardiac, 6.4% vascular, 3.8% thoracic and 10.3% other. The infection site was in the 46.2 peritonitis, 29.5% pneumonia, 3.8%, mediastinitis and 20.8 other. During the sepsis episode other coadjutants used were: Insulin perfusion (60.3%), corticoids (38.5%) and prophylactic low weigh heparin (78.2%). The 88% of the patients didn't received renal replacement. The 28 day mortality was 42.3%. We found 4/78 serious bleeding complications (5%), two of them fatal.

Conclusion: We need specific trials in the subgroup of surgical patients, especially nosocomial ones, due to the high mortality. The use of different therapies to lower the mortality is e encouraged. In our cohort the survival rate of patients treated with drotrecogin alpha was 57.7% with a low incidence of bleeding if we apply the measures related to the selection of patients, control of abdominal drains and coagulation times.