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Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients.
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PMID:  23294562     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT: Analyzing medical records of 979 patients with severe sepsis or septic shock provided some evidence that the use of low-dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) was associated with decreased hospital mortality. However, the benefit was abolished when aspirin and NSAIDs were given together.
Authors:
Maik Sossdorf; Gordon P Otto; Janina Boettel; Johannes Winning; Wolfgang Lösche
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Critical care (London, England)     Volume:  17     ISSN:  1466-609X     ISO Abbreviation:  Crit Care     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
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Nlm Unique ID:  9801902     Medline TA:  Crit Care     Country:  -    
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Languages:  ENG     Pagination:  402     Citation Subset:  -    
Affiliation:
Clinic for Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany. wolfgang.loesche@med.uni-jena.de.
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Journal ID (nlm-ta): Crit Care
Journal ID (iso-abbrev): Crit Care
ISSN: 1364-8535
ISSN: 1466-609X
Publisher: BioMed Central
Article Information
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Copyright © 2013 BioMed Central Ltd
Print publication date: Year: 2012
Electronic publication date: Day: 8 Month: 1 Year: 2013
pmc-release publication date: Day: 8 Month: 1 Year: 2014
Volume: 17 Issue: 1
First Page: 402 Last Page: 402
PubMed Id: 23294562
ID: 4056751
Publisher Id: cc11886
DOI: 10.1186/cc11886

Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients
Maik Sossdorf12 Email: maik.sossdorf@med.uni-jena.de
Gordon P Otto13 Email: gordon.otto@med.uni-jena.de
Janina Boettel2 Email: janina.boettel@med.uni-jena.de
Johannes Winning1 Email: johannes.winning@med.uni-jena.de
Wolfgang Lösche12 Email: wolfgang.loesche@med.uni-jena.de
1Clinic for Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany
2Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany
3Department of Internal Medicine, Division of Nephrology, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany

Various retrospective clinical studies have shown that pre- and in-hospital use of low-dose aspirin was associated with a reduced mortality [1-4], but there is no evidence that NSAIDs may have a similar benefit [1,5]. We studied the medical records of 979 patients with severe sepsis or septic shock who were admitted to a university hospital surgical intensive care unit (ICU). Exclusion criteria were ICU stay of less than 48 hours, age of more than 18 years, and pregnancy. The study was approved by the local ethics committee. Investigators were not required to ask patients for informed consent.


Findings

Ninety-three patients had received NSAIDs (that is, ibuprofen, diclofenac, or indomethacin) during their ICU stay. There was no difference in APACHE (Acute Physiology and Chronic Health Evaluation) II score at ICU admission, but there were significant differences in age, gender, and length of ICU stay. In-hospital mortality was about 10% lower in NSAID users in comparison with non-users (Table 1). Medication during ICU stay with low-dose aspirin, clopidogrel, or statins, all three of which are believed to have a benefit on the outcome in sepsis, is also indicated in Table 1. A model of stepwise logistic regression with in-hospital mortality as a dependent variable and age, gender, APACHE II score, and the administration of NSAIDs, aspirin, clopidogrel, and statins as independent variables indicated that administration of aspirin during ICU stay was associated with a decreased mortality indicated by an odds ratio (OR) of 0.57 (95% confidence interval 0.39 to 0.83) but that NSAIDs, clopidogrel, statins, and gender were without significant effects. However, when patients on aspirin were excluded from the analysis, NSAIDs were also associated with a reduction of the in-hospital mortality (OR = 0.50, 0.26 to 0.94). On the other hand, the benefit of aspirin (acetylsalicylic acid) was completely abolished in those patients who also received NSAIDs (OR = 1.12, 0.55 to 2.25).

The data of the present study indicate that, given separately, both aspirin and NSAIDs may reduce mortality in patients with sepsis. The interaction between aspirin and NSAIDs needs to be considered in forthcoming trials looking for benefits of either compound in patients with sepsis. We speculate that the lack of benefit of parallel use of aspirin and NSAIDs is due to a higher bleeding risk or anti-inflammatory action or both.


Abbreviations

APACHE II: Acute Physiology and Chronic Health Evaluation II; ICU: intensive care unit; NSAID: non-steroidal anti-inflammatory drug; OR: odds ratio.


Competing interests

The authors declare that they have no competing interests.


Acknowledgements

This study was supported by the German Federal Ministry of Education and Research within the 'Center for Sepsis Control and Care'.


References
Eisen DP,Manifold beneficial effects of acetyl salicylic acid and non-steroidal anti-inflammatory drugs on sepsisIntensive Care MedYear: 2012171249125710.1007/s00134-012-2570-822531881
Winning J,Neumann J,Kohl M,Claus RA,Reinhart K,Bauer M,Lösche W,Antiplatelet drugs and outcome in mixed admissions to an intensive care unitCrit Care MedYear: 201017323710.1097/CCM.0b013e3181b4275c19770746
Winning J,Reichel J,Eisenhut Y,Hamacher J,Kohl M,Deigner HP,Claus RA,Bauer M,Lösche W,Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanismsPlateletsYear: 200917505710.1080/0953710080250336819172522
Sanchez MA,Thomas CB,O'Neal HR,Do aspirin and statins prevent severe sepsis?Curr Opin Infect DisYear: 20121734535010.1097/QCO.0b013e3283520ed722395760
Bernard GR,Wheeler AP,Russell JA,Schein R,Summer WR,Steinberg KP,Fulkerson WJ,Wright PE,Christman BW,Dupont WD,Higgins SB,Swindell BB,The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study GroupN Engl J MedYear: 19971791291810.1056/NEJM1997032733613039070471

Tables
[TableWrap ID: T1] Table 1 

Characteristics of the patients included in the study


Variables All patients Without NSAIDs With NSAIDs P valuea
Number of patients 979 886 93
Age, yearsb 67 (56-75) 67 (57-75) 61 (49-71) 0.001
Males/Females, percentage 66.2/33.8 64.7/35.3 81.6/19.4 0.002
APACHE II scoreb 23 (16-29) 23 (16-29) 22 (17-26) 0.160
Length of stay in ICU, daysb 13 (6-23) 12 (5-22) 25 (14-18) 0.0001
Hospital mortality, percentage 42.0 42.9 33.3 0.076
Co-medication, percentage
 Aspirinc 28.0 26.7 39.8 0.008
 Clopidogrel 6.2 6.5 3.2 0.208
 Statins 21.2 20.4 29.0 0.054

aSignificant differences between patients without and those with non-steroidal anti-inflammatory drugs (NSAIDs); bvalues are presented as mean (range); c100 mg/day. APACHE II, Acute Physiology and Chronic Health Evaluation II; ICU, intensive care unit.



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