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Open Access

Timing of drotrecogin alfa (activated) treatment in severe sepsis

  • Goda Choi1, 2Email author,
  • Anne-Cornélie JM de Pont1 and
  • Marcus J Schultz1
Critical Care200610:419

Published: 15 August 2006


Intensive Care UnitEarly TreatmentSevere SepsisOrgan DysfunctionHospital Mortality

The effect of the timing of drotrecogin alfa (activated) (DrotAA) treatment on the outcome of severe sepsis was recently evaluated, using the integrated clinical trial database INDEPTH. The evaluation demonstrated an association between earlier treatment (i.e. treatment within 24 hours of the appearance of first organ dysfunction) and lower patient mortality [1].

We assessed the timing of DrotAA treatment in our own (mixed) intensive care unit over a 3-year period. We selected all patients treated with commercial DrotAA since its availability in The Netherlands. Patients were treated with DrotAA according to the national guidelines [2].

As the results presented in Table 1 show, patients treated within 24 hours were younger and more often had pneumo-sepsis (45% versus 9%, P = 0.03), which was due to community-acquired pneumonia in 12 out of 14 cases (86%). Streptococcus pneumoniae was the most frequently involved pathogen in these pneumonia patients (seven of 12 cases, 58%). Notably, and in contrast to the analysis of the INDEPTH data, hospital mortality rates were comparable between early treatment and late treatment (38% versus 36%, P = 0.93).
Table 1

Baseline patient characteristics based on the time to treatment


0–24 hours (n = 29)

>24 hours (n = 11)

P value

Age (years)

51.5 ± 17.6

67.4 ± 9.9


Male sex

13 (45%)

3 (27%)


Acute Physiology and Chronic Health Evaluation II score

23.9 ± 5.5

26.9 ± 9.8


Time from first organ dysfunction to start of treatment (hours)

12.2 ± 6.8

45.7 ± 21.8


Number of organ dysfunctions

3.6 ± 1.2

3.3 ± 1.3


Mechanical ventilation

25 (86%)

11 (100%)



28 (97%)

10 (91%)


Recent surgery

8 (28%)

6 (55%)


Primary site of infection


   Respiratory system

13 (45%)

1 (9%)



8 (28%)

5 (45%)



2 (7%)

2 (18%)



6 (2%)

3 (27%)


Data presented as mean ± standard deviation or as n (%). aStudent's t test. bChi-square test.

In this small study evaluating DrotAA treatment practice in our intensive care unit, patients treated earlier were younger and more often had community-acquired pneumonia. Given that patients with community-acquired pneumonia seem to benefit most from DrotAA treatment [3], it would be interesting to identify differences in primary sites of infection between early treatment and late treatment within the INDEPTH data.

Authors' response

Jean-Louis Vincent, James O'Brien Jr, Arthur Wheeler, Xavier Wittebole, Rekha Garg, Benjamin L Trzaskoma and David P Sundin

We thank Dr Choi and colleagues for their interesting comments. We checked the database with Eli Lilly, and we found no differences in the sources of infection according to the timing of intervention.


DrotAA = : 

drotrecogin alfa (activated).


Authors’ Affiliations

Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands


  1. Vincent JL, O'Brien J Jr, Wheeler A, Wittebole X, Garg R, Trzaskoma BL, Sundin DP: Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatment in severe sepsis. Crit Care 2006, 10: R74. 10.1186/cc4909PubMed CentralView ArticlePubMedGoogle Scholar
  2. Girbes ARJ, Bakker J, van Deuren M, van Hout BA, van Leeuwen SJ, Levi M, Schultz MJ, van Zanten ARH: Toepassing drotrecogin alpha, geactiveerd proteine C (aPC) bij de behandeling van ernstige sepsis. Neth J Crit Care 2005, 9: 165-166.Google Scholar
  3. Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, Maki DG, Bates B, Yan SC, Dhainaut JF: Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study. Crit Care Med 2005, 33: 952-961. 10.1097/01.CCM.0000162381.24074.D7View ArticlePubMedGoogle Scholar


© BioMed Central Ltd 2006