• Gordon R Bernard.
• Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
• Crit. Care Med. 2003 Jan 1;31(1 Suppl):S85-93.

ObjectiveTo review the data supporting drotrecogin alfa (activated) for severe sepsis treatment.Data SourcesPublished research and data from the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.Data Extraction And SynthesisThe coagulation cascade and intense inflammation play a central role in the development of organ failure due to severe sepsis. Drotrecogin alfa (activated) has anti-inflammatory, antithrombotic, profibrinolytic, and other properties that may explain the beneficial results seen in both animal models and humans with severe sepsis. Drotrecogin alfa (activated) produces a robust reduction in the mortality rate of patients with severe sepsis that is evident across nearly every subgroup examined in the phase III clinical trial and has an acceptable safety profile with bleeding during infusion as the only significant risk associated with therapy. The relative risk reductions for mortality seen in Gram-negative, Gram-positive, pneumonia, abdominal sources, shock, and nonshock are similar to the intent-to-treat population, 19.4%. Treatment also increases days alive and free from mechanical ventilation and shock.ConclusionsCoagulopathy and systemic inflammation are almost universal in patients with severe sepsis. Treatment of this disorder with drotrecogin alfa (activated) directly addresses these derangements and substantially reduces morbidity and mortality rates with potential for bleeding during infusion as the only known risk.

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