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


            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.


            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


            All patients

            Without NSAIDs

            With NSAIDs

            P valuea

            Number of patients





            Age, yearsb

            67 (56-75)

            67 (57-75)

            61 (49-71)


            Males/Females, percentage





            APACHE II scoreb

            23 (16-29)

            23 (16-29)

            22 (17-26)


            Length of stay in ICU, daysb

            13 (6-23)

            12 (5-22)

            25 (14-18)


            Hospital mortality, percentage





            Co-medication, percentage
















            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.


            APACHE II: 

            Acute Physiology and Chronic Health Evaluation II


            intensive care unit


            non-steroidal anti-inflammatory drug


            odds ratio.



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

            Authors’ Affiliations

            Clinic for Anaesthesiology and Intensive Care Medicine, University Hospital Jena
            Center for Sepsis Control and Care, University Hospital Jena
            Department of Internal Medicine, Division of Nephrology, University Hospital Jena


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            © BioMed Central Ltd 2013