Temporal trends of circulating nitric oxide and pro-inflammatory cytokine responses ex vivo in intra-abdominal sepsis: results from a cohort study.
OBJECTIVE
To evaluate the association of pro-inflammatory mediators with organ dysfunction and adverse outcome in intra-abdominal sepsis patients.


METHODS
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.
Division of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Havana, Cuba. miriamojeda@infomed.sld.cu
Miriam
M
Ojeda Ojeda
Hilev
H
Larrondo Muguercia
Abel
A
Magdariaga Figuerola
Alfredo
A
Sánchez Valdivia
Ingrid
I
Rodríguez Alonso
Carmen
C
Valenzuela Silva
Elizeth
E
García Iglesias
Emma
E
Domínguez Alonso
Wim A
WA
Buurman
Manuel de Jesús
Mde J
Araña Rosaínz
D034841:Abdominal Cavity / Q000382:microbiology*; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003428:Cross Infection / Q000097:blood / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D016207:Cytokines / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D018805:Sepsis / Q000097:blood* / Q000276:immunology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide