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Drotrecogin Alfa (Activated) in Severe Sepsis: Long-Term Outcomes

　　Derek C. Angus, MB, ChB, MPH,[9] of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, discussed the long-term outcomes of severe sepsis patients treated with drotrecogin alfa (activated).
　　There are concerns that the 28-day cut off may be inadequate as an end point, especially for sepsis patients. Septic patients were shown to have an increased risk of death up to 5 years after the septic episode.[10] At least 90 days has been proposed as a primary end point for follow up of septic patients.[11] In the PROWESS trial, 40% of the patients at day 28 were still in the hospital. The extended follow up for the years 2001 to 2002 was presented. This was a separate study aiming also to subgroup analysis. From the 1690 patients originally enrolled in the study, 1127 survivors were followed up (93 were lost). There were no significant differences between the lost patients and those who were followed up. A 5.2% absolute decrease in hospital mortality was demonstrated. When follow up was extended for 90 days, there was still an overall difference in mortality favoring drotrecogin alfa (activated), but as the follow up extended more in time, the difference was less pronounced until it was lost (P = .048 for 90 days survival, P = .097 for 30 months survival), although there was a 32% increase in the median survival. In subgroup analysis, age was not a significant predictive factor for mortality, although there was a 94% increase in median survival time for the patients older than 60 years. Disease severity as measured by the APACHE II score had a significant effect. Those with an APACHE II score of less than 25 had manifested a constantly increasing (but not statistically significant) 30-month mortality when they had received drotrecogin alfa (activated). Cautious use of drotrecogin alfa (activated) should be practiced in these patients, and further studies are underway. On the other hand, patients with an APACHE II score higher than 25 had a significantly lower mortality during the whole spectrum of the 30 months follow up, with a P = .0009. For these patients, there was a 534% increase in median survival.
　　In conclusion, it appears that improved survival continues to persist throughout the 2.5 years follow up for septic patients treated with drotrecogin alfa (activated) and that there is also a remarkable increase in median survival. Effects are unclear for those patients with less severe sepsis. The maximum benefit is evident for the sicker patients, thus underlying the FDA label that approves drotrecogin alfa (activated) for "severe sepsis and especially for patients at high risk."