CIRCULATING METHEMOGLOBIN AND NITRITE NITRATE CONCENTRATIONS AS INDICATORS OF NITRIC-OXIDE OVERPRODUCTION IN CRITICALLY ILL CHILDREN WITH SEPTIC SHOCK/

Objectives: To examine the relationship between circulating methemoglo bin and nitrite/nitrate concentrations and to compare these markers of nitric oxide overproduction with clinical variables in children diagn osed with septic shock. Design: Prospective, controlled, clinical stud y. Setting: Pediatric intensive care unit and outpatient clinic in a c hildren's hospital. Patients: Twenty-two children diagnosed with septi c shock and ten age-matched healthy control patients. Interventions: P atients diagnosed with septic shock had blood specimens taken on study entry and every 6 hrs for 72 hrs for methemoglobin and nitrite/nitrat e determinations. Single blood specimens were obtained from controls. Measurements and Main Results: Circulating methemoglobin and nitrite/n itrate concentrations were significantly higher in children diagnosed with septic shock in comparison with healthy control children (p = .01 and .05, respectively). Peak nitrite/nitrate concentrations correlate d with serum creatinine (r(2) = .19; p = .04) and were inversely corre lated with arterial pH (r(2) = .28; p = .01) and urine output (r(2) = .21; p = .03) when analyzed by log-linear regression. There were no si gnificant relationships between methemoglobin and nitrite/nitrate or b etween methemoglobin and any other clinical variable. Conclusions: Cir culating methemoglobin and nitrite/nitrate concentrations are increase d in children diagnosed with septic shock. Plasma nitrite/nitrate valu es correlate with selected clinical variables in these children. Circu lating methemoglobin measurements are not superior to plasma nitrite/n itrate concentrations as an indicator of endogenous overproduction of nitric oxide in children diagnosed with septic shock. A need remains t o develop markers of endogenous nitric oxide activity that have greate r accuracy and reliability.