There has been growing optimism in the field of critical care medicine owing to our better understanding of the pathophysiology underlying severe sepsis. We now recognize that hemostatic abnormalities appear to be almost universal in patients with severe sepsis, with the coagulation and fibrinolytic systems being profoundly deregulated during sepsis. Drotrecogin alfa (activated) has clearly demonstrated outcome benefit in patients with severe sepsis, perhaps attributed to its multiple mechanisms of action, including modulation of the inflammatory responses, and displaying both antithrombotic and profibrinolytic properties.5
Threatening bleeds and intracranial hemorrhage appear to be uncommon in approximately 2,786 treated patients in controlled and open-label trials (0.4% and 0.5%, respectively). The reduction in mortality with this drug is far greater than the risk of a serious bleed, especially in the high-risk, severe septic population. Although some would have expected overwhelming adoption of this novel therapy in both academic and community hospital settings, it appears that clinicians have been slow to adopt this highly beneficial, although cost-effective therapy. This is surprising since the study results were very positive, particularly in high-risk patients, and presented widely in the medical domain. Interinstitutional and interregional practice variations in employing this therapy may likely have several causes, including local practice style or habit, inertia, and economic pressures from hospital administrators and pharmacists. Given the magnitude of the problem of severe sepsis, a rigorous evaluation should be undertaken to further understand the nonscientific circumstances that have potentially influenced the implementation of drotrecogin alfa (activated) therapy for severe sepsis in ICUs. For now, it should be our desire as physicians to embrace new life-saving technology.