Adverse events and clinical outcome associated with drotrecogin alfa-activated: A single-center experience of 498 patients over 8 years

TY - JOUR

T1 - Adverse events and clinical outcome associated with drotrecogin alfa-activated

T2 - A single-center experience of 498 patients over 8 years

AU - Boyle, Alison

AU - McKenzie, Catherine

AU - Yassin, Sarah

AU - McLuckie, Angela

AU - Wyncoll, Duncan

PY - 2012/6

Y1 - 2012/6

N2 - Purpose: Licensed in 2002 for severe sepsis, drotrecogin alfa-activated (DAA) remains a much debated therapy particularly with respect to outcomes and a potentially increased risk of serious bleeding events (SBEs). Recent publications have suggested a significantly increased incidence of SBEs and death in those with baseline bleeding risks (BBRs). Our center is one of the highest prescribers of DAA worldwide; we describe our experience of SBEs and other clinical outcomes.Methods: Prospectively collected data using a clinical guideline audit tool and database to track outcome and adverse events of DAA-treated severe sepsis patients were analyzed.Results: Four hundred ninety-eight patients received DAA over an 8-year period. Hospital, critical care, and 28-day mortalities were 46.2%, 39.6%, and 35.1%, respectively. Contraindications were identified for 40 (8.0%) patients, of whom 24 (4.8%) had BBRs. Hospital mortality was 47.5% (19/40) for patients with any contraindication and 45.8% (11/24) for those with a BBR. Seventy-six (15.3%) bleeding events were reported; 22 (4.4%) were considered serious. Hospital mortality was 60.5% for patients with any bleeding event and 77.3% for those with SBEs.Conclusions: This large single-center case series demonstrates that DAA has an incidence of SBEs similar to initial clinical trials. As expected, SBEs were associated with a poor outcome.

AB - Purpose: Licensed in 2002 for severe sepsis, drotrecogin alfa-activated (DAA) remains a much debated therapy particularly with respect to outcomes and a potentially increased risk of serious bleeding events (SBEs). Recent publications have suggested a significantly increased incidence of SBEs and death in those with baseline bleeding risks (BBRs). Our center is one of the highest prescribers of DAA worldwide; we describe our experience of SBEs and other clinical outcomes.Methods: Prospectively collected data using a clinical guideline audit tool and database to track outcome and adverse events of DAA-treated severe sepsis patients were analyzed.Results: Four hundred ninety-eight patients received DAA over an 8-year period. Hospital, critical care, and 28-day mortalities were 46.2%, 39.6%, and 35.1%, respectively. Contraindications were identified for 40 (8.0%) patients, of whom 24 (4.8%) had BBRs. Hospital mortality was 47.5% (19/40) for patients with any contraindication and 45.8% (11/24) for those with a BBR. Seventy-six (15.3%) bleeding events were reported; 22 (4.4%) were considered serious. Hospital mortality was 60.5% for patients with any bleeding event and 77.3% for those with SBEs.Conclusions: This large single-center case series demonstrates that DAA has an incidence of SBEs similar to initial clinical trials. As expected, SBEs were associated with a poor outcome.

KW - Drotrecogin alfa-activated

KW - Severe sepsis

KW - Bleeding

KW - SEVERE SEPSIS

KW - PROTEIN-C

KW - SAFETY

KW - HEMORRHAGE

U2 - 10.1016/j.jcrc.2011.07.004

DO - 10.1016/j.jcrc.2011.07.004

M3 - Article

SN - 0883-9441

VL - 27

SP - 320.e7-300.e12

JO - Journal of Critical Care

JF - Journal of Critical Care

IS - 3

ER -