NDLI: Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort

Content Provider	Springer Nature : BioMed Central
Author	Hodder, Richard V Hall, Richard Russell, James A Fisher, Harold N Lee, Bobbie
Abstract	Introduction Early multimodal treatment of severe sepsis, including the use of drotrecogin alfa (activated) (DrotAA) when indicated, is considered essential for optimum outcome. However, predicting which infected patients will progress to severe sepsis and the need for aggressive intervention continues to be problematic. We therefore wished to explore whether there were any potential early markers that might predict improved survival in response to early use of DrotAA in patients with severe sepsis. In particular, in the dynamic setting of severe sepsis, we postulated that changes in markers reflecting evolving rather than baseline clinical status might guide therapy. Methods Data on a cohort of 305 Canadian patients from the open label ENHANCE trial of DrotAA in severe sepsis was retrospectively analyzed to search for potential clinical predictors of outcome in severe sepsis. Patients received a 96-hour infusion of DrotAA and were followed for 28 days. The association between time to treatment and mortality within subgroups defined by dynamic changes in various potential markers was explored. Results Mortality at 28 days was 22.6% and the variables of age, time to treatment, and early changes in serum creatinine and platelet count were identified by logistic regression as independent predictors of mortality. Across all age ranges, 28-day mortality was lower when DrotAA was administered within 24 hours of first sepsis-induced organ dysfunction compared to administration after 24 hours for both subgroups of patients defined by changes in platelet count and creatinine within the first day. Conclusions These findings suggest that when indicated, treatment with DrotAA should be initiated as soon as possible, regardless of age. Trial Registration Previous trial registration number: NCT00568893
Related Links	https://ccforum.biomedcentral.com/counter/pdf/10.1186/cc7893.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	13648535
DOI	10.1186/cc7893
Journal	Critical Care
Issue Number	3
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2009-05-20
Access Restriction	Open
Subject Keyword	Intensive Critical Care Medicine Emergency Medicine Severe Sepsis Organ Dysfunction Sequential Organ Failure Assessment Drotrecogin Alfa Canadian Cohort
Content Type	Text
Resource Type	Article
Subject	Critical Care and Intensive Care Medicine
Journal Impact Factor	8.8/2023
5-Year Journal Impact Factor	10.4/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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