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


CONCLUSIONS
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.
Kanji
Salmaan
S
Department of Pharmacy, The Ottawa Hospital, Ottawa Health Research Institute, 501 Smyth Road, Room 1818, H1H 8L6, Ottawa, ON, Canada. skanji@ottawahospital.on.ca
Perreault
Marc M
MM
Chant
Clarence
C
Williamson
David
D
Burry
Lisa
L
D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000075202:Contraindications; D004363:Drug Utilization; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009864:Ontario / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D011792:Quebec / Q000453:epidemiology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated