A large, single-centre UK registry of drotrecogin alfa-activated use

Introduction

As one of the few treatment interventions to demonstrate mortality efficacy at a randomized controlled trial level [1], the prescription of drotrecogin alfa-activated (DrotAA) (Xigris™), where appropriate, plays an important role in the management of severe sepsis. However, concerns regarding the potential for serious bleeding events have helped sustain a degree of scepticism regarding the use of DrotAA [2]. As early adopters of evidence-based medicine, Cardiff Critical Care Unit has prescribed DrotAA since late 2002 and has considerable experience with respect to its use. The aim of this study was to demonstrate the safety profile and efficacy of DrotAA treatment within a large, 29-bed university hospital critical care unit.

Methods

Demographic data were obtained from the unit's daily updated Riyadh ICU programme database and clinical data were collected from patients' medical notes and observation charts. All data were prospectively entered into our DrotAA registry, the results of which are shown below.

Results

Between October 2002 and November 2005, 133 patients with severe sepsis were treated with DrotAA. The mean age was 61 years (range: 20–87 years) and 54% were male. The mean admission APACHE II score was 22 (range: 11–48), and on day 1 of DrotAA infusion the median number of organs that failed was 2.0 (range: 0–4), 129/133 (97%) were mechanically ventilated and 131/133 (98.5%) were on vasopressors. The median time to start DrotAA after documented diagnosis of severe sepsis was 12.6 hours (range: 0–41 hours) and the median duration of DrotAA infusion was 89.5 hours (range: 10–105 hours). The incidence of serious (life-threatening) bleeding events was 2.3% (n = 3): gastrointestinal (n = 1), intraabdominal (n = 1) and intrathoracic (n = 1); all were nonfatal and there were no intracranial bleeds. The 28-day mortality was 31.6%, the ICU mortality was 33.1%, the hospital mortality was 36.8% and the 1-year mortality was 47%.

Conclusion

This is one of the largest UK registries of DrotAA usage published to date. Our results demonstrate a very low incidence of serious bleeding events associated with DrotAA treatment (2.3% vs 3.5% in PROWESS); it is interesting to note that all three adverse events occurred prior to 2004. This detail, combined with our low median time to start DrotAA infusion (which has steadily decreased over the past 4 years), would suggest the presence of a learning curve for DrotAA usage on ICUs. It is also encouraging to note that our overall hospital mortality was lower than the predicted APACHE II hospital mortality for these patients (36.8% vs 42.4%). Finally, this is one of the first UK studies to describe long-term mortality outcome in patients receiving DrotAA therapy. Further studies are required to more formally assess the impact of DrotAA treatment on long-term survival from severe sepsis.