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Outcome of patients receiving two or more infusions of activated protein C: a single-centre experience


Patients frequently develop a second discrete episode of sepsis during an ICU stay such as ventilation-acquired pneumonia (VAP), or patients may have a second ICU admission unrelated to their initial presentation. In the PROWESS [1] study, drotrecogin alfa (DAA) could not be given twice to the same patient; yet this may be a potentially life-saving intervention when a second episode of severe sepsis occurs.


We conducted a retrospective study of patients who received more than one infusion of DAA in our combined adult surgical and medical ICU. The attending ICU physician determined who received a second course of DAA.


During the 6-year study period (November 2002 to October 2008) 354 patients were treated with DAA, seven patients were identified who received DAA twice and one patient received three infusions. Five patients treated with two infusions survived to be discharged home. Four patients were admitted to the ICU on two separate occasions, for these patients one infusion of DAA was given on each admission, three survived, and the median interval between admissions was 17 months (range 7 to 23). Four patients received a second infusion of DAA on the same ICU admission, the median interval between the first and second infusion was 3.5 days (range 3 to 12), and two survived. The median age was 67 years (range 41 to 77) with a median of four organ failures per patient (range 2 to 5). Those patients who received DAA twice on the same admission developed VAP or a line-related infection. Patients admitted for a second time had a different discrete episode of septic shock unrelated to their first admission. There was one major bleeding episode requiring cessation of DAA and a blood transfusion. This patient was found to have a duodenal ulcer. Six infusions of DAA were not completed, three patients died whilst receiving their second infusion, three courses were terminated due to rapid improvement in the patient's condition. No patient experienced significant bleeding during their second infusion.


This is the first case series to report the outcome of patients who have received multiple courses of DAA. The incidence of repeat episodes of sepsis during a single admission or the precise rate of recurrent sepsis during ICU admissions is not easily identified in the current literature. Our findings are limited by the heterogeneous nature of the patient group and the lack of strict criteria defining who received a second course of DAA. A second course of DAA treatment may be justified on a case-by-case basis.


  1. 1.

    Bernard GR, et al.: N Engl J Med. 2001, 344: 699-670. 10.1056/NEJM200103083441001

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Correspondence to A Retter.

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Retter, A., Lippett, S., Beale, R. et al. Outcome of patients receiving two or more infusions of activated protein C: a single-centre experience. Crit Care 14, P406 (2010).

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  • Severe Sepsis
  • Duodenal Ulcer
  • Median Interval
  • Bleeding Episode
  • Repeat Episode