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Temporal trends of circulating nitric oxide and pro-inflammatory cytokine responses ex vivo in intra-abdominal sepsis: results from a cohort study

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Abstract

Objective and design

To evaluate the association of pro-inflammatory mediators with organ dysfunction and adverse outcome in intra-abdominal sepsis patients.

Subjects

Twenty-one patients admitted to the Intensive Care Unit (ICU) were prospectively included in the study. Only patients with surgical diagnosis of intra-abdominal sepsis were enrolled.

Results

Tumor necrosis factor-α (TNFα) and interleukin (IL)-6 produced ex vivo were significantly lower in non-survivors on admission (p = 0.021) and day 2 (p = 0.013), respectively. Nitric oxide (NO x ) levels were significantly higher in non-survivors from the onset of sepsis and until day 4 after diagnosis (p < 0.05). Circulating lymphocyte counts were lower in non-survivors after admission over time, but there was no association with impaired cytokine production in this group of patients during the entire follow-up. All non-survivors developed nosocomial pneumonia concomitantly with multiple organ dysfunction and septic shock. There was a significant correlation between nitric oxide (NO x ) concentrations and the sequential organ failure assessment (SOFA) score at day 2 (r = 0.598, p = 0.009), and ICU stay (r = 0.605, p = 0.006). Continuously high NO x levels correlated with organ failure. The pro-inflammatory mediators TNFα, IL-6 and NO x , and also the Simplified Acute Physiology Score II (SAPS-II), discriminate survivors from non-survivors. According to logistic regression models, although these parameters are independently associated with the outcome, they do not improve the predictive power of the SAPS-II score for mortality risk.

Conclusions

Disturbances in inflammatory responses and increase in NO x generation seem to characterize early intra-abdominal sepsis, in which immune suppression is associated with an increased susceptibility to nosocomial infections. Sequential NO x determinations could be a useful approach for improving the management of patients with intra-abdominal sepsis.

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Author notes

  1. Miriam Ojeda Ojeda

    Present address: Department of Immunology, National Institute of Endocrinology, 10400, Havana, Cuba

Authors and Affiliations

  1. Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Havana, Cuba

    Miriam Ojeda Ojeda, Abel Magdariaga Figuerola, Ingrid Rodríguez Alonso & Manuel de Jesús Araña Rosaínz

  2. Critical Care Unit, Hospital “Hermanos Ameijeiras”, Havana, Cuba

    Hilev Larrondo Muguercia & Alfredo Sánchez Valdivia

  3. Division of Clinical Trials, Center for Genetic Engineering and Biotechnology, Havana, Cuba

    Carmen Valenzuela Silva & Elizeth García Iglesias

  4. Department of General Surgery, University of Maastricht, Maastricht, The Netherlands

    Wim A. Buurman

  5. Department of Immunology, National Institute of Endocrinology, 10400, Havana, Cuba

    Emma Domínguez Alonso

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  1. Miriam Ojeda Ojeda
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Correspondence to Miriam Ojeda Ojeda.

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Responsible Editor: Artur Bauhofer.

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Ojeda Ojeda, M., Larrondo Muguercia, H., Magdariaga Figuerola, A. et al. Temporal trends of circulating nitric oxide and pro-inflammatory cytokine responses ex vivo in intra-abdominal sepsis: results from a cohort study. Inflamm. Res. 60, 289–297 (2011). https://doi.org/10.1007/s00011-010-0267-4

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  • DOI: https://doi.org/10.1007/s00011-010-0267-4

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