The use of drotrecogin alfa (activated) in solid organ transplant patients: a case series.
BACKGROUND
Drotrecogin alfa (activated) (DAA), a recombinant human activated protein C, is indicated for the reduction of mortality in patients with severe sepsis who have a high risk of death. In the initial trial, DAA demonstrated a significant reduction in mortality at 28 days for patients treated with DAA in comparison with standard supportive treatment (placebo). However, solid organ transplant recipients were excluded from the study. Transplant recipients are at an increased risk for sepsis and there is minimal literature describing the safety and efficacy of DAA in the transplant population.


METHODS
Thirteen solid organ transplant recipients who received DAA between November 2001 and January 2004 were included in this case series. Patients were prospectively identified and data collection occurred concurrently and by retrospective chart review. All patients met the DAA use criteria based on the institutional standard protocol.


RESULTS
We report the outcomes of the 13 adult transplant patients who received a total of 14 courses of DAA for severe sepsis. At the time of DAA initiation, all patients required mechanical ventilation, 86% necessitated vasopressor support, and had a median of 3 dysfunctional organs. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score at initiation was 30. Overall, hemodynamic stability and APACHE II score improved at the end of DAA infusion. Causes of early discontinuation were bleeding (57%), scheduled procedure (14%), increased international normalized ratio (14%), and death (14%). In-hospital, 28-day, and 1-year mortality was 69%, 62%, and 83%, respectively.


CONCLUSIONS
DAA appears to be safe with appropriate monitoring. However, transplant recipients had a higher incidence of bleeding events leading to early discontinuation of DAA. Efficacy is difficult to assess without an appropriate control group for comparison.
Berkman
S
S
Department of Pharmacy Services, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Weimert
N A
NA
Taber
D J
DJ
Baillie
G M
GM
Lin
A
A
Baliga
P
P
Chavin
K D
KD
D018806:APACHE; D000328:Adult; D000368:Aged; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated