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Drotrecogin alfa (activated): diffusion from clinical trials to clinical practice

Published online by Cambridge University Press:  01 March 2008

S. Ridley ,
A. Lwin ,
D. Wyncoll ,
S. Lippett ,
D. Watson ,
K. Gunning  and
D. Higgins
S. Ridley*
Affiliation:
Glan Clwyd Hospital, Department of Anaesthesia and Intensive Care, Rhyl, Denbighshire, UK
A. Lwin
Affiliation:
Norfolk & Norwich University Hospital, Department of Acute and General Medicine, Norwich, UK
D. Wyncoll
Affiliation:
Guy’s & St Thomas’ NHS Foundation Trust, Department of Critical Care, London, UK
S. Lippett
Affiliation:
Guy’s & St Thomas’ NHS Foundation Trust, Department of Critical Care, London, UK
D. Watson
Affiliation:
University Hospitals Coventry and Warwickshire NHS Trust, Department of Anaesthesia and Intensive Care, London, UK
K. Gunning
Affiliation:
Addenbrookes Hospital, Department of Anaesthesia and Intensive Care, Cambridge, UK
D. Higgins
Affiliation:
Southend NHS Trust, Department of Anaesthesia and Intensive Care, London, UK
*
Correspondence to: Saxon Ridley, Department of Anaesthesia and Intensive Care, Glan Clwyd Hospital, Rhyl, Denbighshire LL18 5UJ, UK. E-mail: saxon@ridley.waitrose.com; Tel: +44 1745 583910; Fax: +44 1745 583143
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Summary

Backgound and objective

Although the PROWESS trial demonstrated a mortality benefit, subsequent studies in different patient populations have not reproduced the effect. As a result, concerns have been expressed about the clinical effectiveness of drotrecogin alfa (activated). Therefore the aim of this audit was to review the clinical impact of drotrecogin alfa (activated) when used outside clinical trials.

Methods

A retrospective review of ICU charts and medical records of patients who had received drotrecogin alfa (activated) in the five largest users of drotrecogin alfa (activated) in England. Patients characteristics details at ICU admission and vital status at hospital discharge were recorded. The severity of illness was assessed by the APACHE II score (using first 24 h admission data) and the number of organ dysfunctions. Adverse incidents were recorded and any sequence effect explored.

Results

In all, 351 patients received drotrecogin alfa (activated) between December 2002 and November 2005. Of those, 201 (57.2%) were male, and 177 (50.4%) were admitted after recent surgery. The patients’ average age was 61.8 yr. The mean admission APACHE II score was 23.3 and the average number of dysfunctional organs on admission was 3.3. The hospital mortality was 46.7% (164 deaths). The expected number of deaths calculated by using the APACHE II risk of death was 173 (49.3%) and by number of sepsis induced organ failures 210 (59.7%). Overall, there were 33 (9.4%) adverse incidents.

Conclusions

Expected mortality derived from both the APACHE II score and organ dysfunctions suggests that drotrecogin alfa (activated) does reduce mortality. Serious adverse incidents occurred in 5.1% patients; however, the direct contributing effect of drotrecogin alfa (activated) cannot be established from this type of audit.

Keywords

DROTRECOGIN ALPHAMULIPTLE ORGAN FAILURESEPSISCRITICAL CAREMORTALITY AND MORBIDITY
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 3 , March 2008 , pp. 211 - 216
Copyright
Copyright © European Society of Anaesthesiology 2008

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