Circulating methemoglobin & nitrite/nitrate in children with septic shock

Purpose: The inducible isoform of nitric oxide synthase is upregulated by a variety of cells in response to inflammatory stimuli, and produces large amounts of nitric oxide (NO). Although the short half-life of NO makes its direct clinical measurement impractical, its degradation products, nitrite/nitrate (NOx), provide an indirect measure of systemic NO synthesis. Plasma NOx concentrations are elevated in children with septic shock, however, because plasma levels of NOx are influenced by renal function, the validity of NOx as a true index of NO synthesis in this condition is questionable. The purpose of this study was to investigate if methemoelobin (MetHb), the reaction product of NO and Hb, is a better indicator of severity of illness than NOx in children with septic shock. Methods: 22 children ages 19-261 months with the diagnosis of septic shock, and 10 age-matched healthy children were enrolled. Demographic and clinical data were collected. Blood was obtained upon study entry, and 4 times each day for 72 hours for MetHb, and NOx assays. MetHb was determined by co-oximetry. Plasma nitrate was reduced to nitrite, and nitrite levels were measured using the Griess reaction assay. Results: Peak NOx correlated with peak MetHb (p=0.02), lowest arterial pH (p=0.01), and lowest base deficit (p=0.03). Individual or peak MetHb values did not correlate with any other clinical variables. Septic shock and control patients are compared in the Table. Septic Control (n=22) (n=10) p* Age (mo) 105±16 122±20 NS Mean MetHb (%) 2.4±0.3 1.5+0.1 .007 Peak MetHb (%) 3.4±0.6 1.5±0.1 .003 Mean NOx (uM) 82±18 41±9 .052 Peak NOx (uM) 127±23 41±9 .002 * Unpaired two-tailed Student's t test Conclusions: Plasma MetHb and NOx levels are elevated in children with septic shock. Peak plasma NOx values correlate with peak MetHb and selected clinical indicators of severity of illness in these children. Clinical Implications: Plasma NOx concentrations are more likely to be useful as an indicator of endogenous overproduction of NO than MetHb in children with septic shock.