Measurements of total plasma nitrite and nitrate in pediatric patients with the systemic inflammatory response syndrome.

OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is typified by the presence of fever, hemodynamic changes, and end organ dysfunction. Endothelial cell activation leads to overproduction of nitric oxide, which results in sustained vasodilation and hypotension. This study was undertaken to determine the sensitivity, specificity, and positive and negative predictive values of plasma nitrite/nitrate measurements in identifying patients with clinical characteristics of SIRS, as defined by criteria based on physician diagnosis.
DESIGN: Prospective cohort study with consecutive sampling of patients.
SETTING: Tertiary, multidisciplinary, pediatric intensive care unit (ICU) at Children's Hospital of Wisconsin. PATIENTS: Patients were divided into five groups. There were 16 pediatric controls undergoing elective surgery and 177 pediatric ICU patients without and 46 pediatric ICU patients with physician-diagnosed sepsis, septic shock, SIRS, or sepsis syndrome documented in the medical record (all considered physician-diagnosed sepsis). The 223 pediatric ICU patients included 195 pediatric ICU patients not meeting and 28 pediatric ICU patients meeting predetermined physiologic criteria for SIRS (considered criteria-based sepsis).
INTERVENTIONS: Blood samples were obtained for quantitative nitrite/nitrate analysis at the time of admission to the pediatric ICU and daily until discharge.
MEASUREMENTS AND MAIN RESULTS: Mean plasma nitrite/nitrate concentrations in the controls were 34.5 +/- 12 microM (95th percentile 54 microM). In pediatric ICU patients without and with physician-diagnosed sepsis, mean plasma nitrite/nitrate concentrations were 39 +/- 24 microM (p > .05 compared with controls) and 127 +/- 91 microM (p < .0001 compared with both controls and patients without physician-diagnosed sepsis), respectively. In pediatric ICU patients without and with criteria-based sepsis, the mean total plasma nitrite/nitrate concentrations were 56 +/- 59 microM (p = .008 compared with controls) and 80 +/- 64 microM (p = .003 compared with patients without criteria-based sepsis), respectively. The ability of plasma nitrite/nitrate > 54 microM to identify patients with physician-diagnosed sepsis is characterized as follows: 87% sensitivity, 77% specificity, 50% positive predictive value, and 96% negative predictive value. The ability of plasma nitrite/nitrate > 54 microM to identify patients with criteria-based sepsis is characterized as follows: 61% sensitivity, 68% specificity, 21% positive predictive value, and 92% negative predictive value.
CONCLUSIONS: Clinical diagnosis of SIRS is strongly associated with increased total plasma nitrite/nitrate concentrations in pediatric patients in the pediatric ICU. Many patients with increased nitrite/nitrate concentrations have inflammation without having a clinical diagnosis of SIRS. Our data suggest that increased plasma nitrite/nitrate concentrations are the standard for identifying patients with inflammation in the pediatric ICU.