Evaluating the use of Drotrecogin alfa (activated) in adult severe sepsis: a Canadian multicenter observational study

Abstract

Background: The purpose of this study was to characterize the usage patterns and clinical outcomes of DAA in Ontario and Quebec over a 1-year period.

Methods: All hospitals with DAA on formulary in Ontario and Quebec were invited to participate. Consecutive patients who received DAA from 1 March 2003 to 29 February 2004 were identified retrospectively. Demographic, treatment, and outcome variables were collected via chart review. Descriptive statistics on relevant variables were performed, along with logistic regression to determine relevant risk factors for survival and bleeding.

Results: Thirty-seven sites participated with a total of 261 courses of DAA administered. The overall mortality rate was 45%; age (> 65 years), multiple organ system failure (> 3), and nosocomial source of sepsis were predictors of mortality, whereas early DAA administration (< 12 h) was associated with lower mortality. Serious bleeding events occurred in 10% of the patients. Only 1 case (0.4%) of fatal intracranial bleed was observed. Multiple organ system failure (>/= 4)and relative contraindications to DAA were predictors of bleeding events.

Interpretation: Mortality and bleeding complications associated with the use of DAA were higher than that reported in randomized trials but similar to other usage database. This may be due to the higher severity of illness seen in this cohort of patients. Modifiable risks associated with mortality and bleeding, such as time to treatment, and knowledge of relative contraindications should be targets of further research and future educational efforts in order to optimize the risk-to-benefit ratio of DAA.