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

Inflamm Res. 2011 Mar;60(3):289-97. doi: 10.1007/s00011-010-0267-4. Epub 2010 Oct 26.

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.

MeSH terms

  • Abdominal Cavity / microbiology*
  • Adult
  • Aged
  • Animals
  • Biomarkers / blood
  • Cohort Studies
  • Cross Infection / blood
  • Cross Infection / immunology
  • Cross Infection / microbiology
  • Cross Infection / mortality
  • Cytokines / blood*
  • Cytokines / immunology*
  • Female
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • Nitric Oxide / blood*
  • Prospective Studies
  • ROC Curve
  • Risk Factors
  • Sepsis / blood*
  • Sepsis / immunology*
  • Sepsis / mortality
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide