Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients

  • Maik Sossdorf1, 2,

    Affiliated with

    • Gordon P Otto1, 3,

      Affiliated with

      • Janina Boettel2,

        Affiliated with

        • Johannes Winning1 and

          Affiliated with

          • Wolfgang Lösche1, 2Email author

            Affiliated with

            Critical Care201317:402

            DOI: 10.1186/cc11886

            Published: 8 January 2013

            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.

            Various retrospective clinical studies have shown that pre- and in-hospital use of low-dose aspirin was associated with a reduced mortality [14], 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).
            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.

            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.

            Declarations

            Acknowledgements

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

            Authors’ Affiliations

            (1)
            Clinic for Anaesthesiology and Intensive Care Medicine, University Hospital Jena
            (2)
            Center for Sepsis Control and Care, University Hospital Jena
            (3)
            Department of Internal Medicine, Division of Nephrology, University Hospital Jena

            References

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            Copyright

            © BioMed Central Ltd 2013

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