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

M. Ojeda Ojeda, H. Larrondo Muguercia, A. Magdariaga Figuerola, A. Sanchez Valdivia, I. Rodriguez Alonso, C. Valenzuela Silva, E. Garcia Iglesias, E. Dominguez Alonso, W.A. Buurman, M.D. Arana Rosainz

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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-alpha (TNFalpha) 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 TNFalpha, 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.
Original languageEnglish
Pages (from-to)289-297
JournalInflammation Research
Issue number3
Publication statusPublished - 1 Jan 2011

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