Retrospective observational outcomes for drotrecogin alfa (activated)

Introduction

Grand River Hospital (GRH) is a 495-bed non-teaching, acute care referral center in Southwestern Ontario, supporting regional programs including dialysis, oncology, surgery and stroke thrombolysis. Since the introduction of drotrecogin alfa (activated) (DAA) in 2003, GRH has treated 58 patients with this agent for severe sepsis and septic shock. We sought to compare, where possible, GRH ICU/hospital outcomes and bleeding complications with those from published literature.

Methods

All charts for patients treated with DAA in our CAICU for severe sepsis and septic shock between February 2003 and June 2006 were reviewed retrospectively for infection source, ICU/hospital mortality, survival by age and incidence of hemorrhagic complications. Where possible, we compare our data with those from PROWESS, ENHANCE and a recent Ontario/Quebec-based multicenter usage evaluation. A two-organ system failure threshold for DAA consideration is used. Outcomes were categorized as ICU mortality and hospital mortality, as opposed to 28-day mortality used in PROWESS and ENHANCE.

Results

All 58 patients who received DAA at GRH were included in our analysis. The mean age of patients treated with DAA was 59.4 years. Primary sources of infection were: intra-abdominal 36.2%, respiratory 27.6%, genitourinary 8.6%, and 27.6% from other sources. GRH ICU mortality was 44.8% and hospital mortality was 51.7%. Analysis by age revealed overall survival rates of 78.6% for patients ≤50 years, 54.5% for 51–60 years, 52.9% for 61–70 years, 20% for 71–80 years, and 0% for patients >80 years of age. Hemorrhagic complication rates were higher than in published reports. Of 58 treatments, we recorded a total of nine hemorrhages (15.5%). The mortality rate in this cohort was 33.3%.

Conclusion

These data suggest that 'field performance' of DAA may not be replicating the favorable clinical endpoints as reported in PROWESS. The Ontario Ministry of Health should consider implementing a provincial registry system for patients with severe sepsis and septic shock, empowering ICUs to track relevant demographic, acuity, and outcome data with a view to optimizing DAA use through patient selection and risk stratification.