ObjectiveTo investigate whole body,in vivoarginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients.DesignProspective study.SettingPediatric intensive care unit at a general hospital.PatientsTen consecutive septic patients age 6–16 yrs.InterventionsSeptic patients received an 8-hr primed, constant intravenous tracer infusion of l-[guanidino-15N2]arginine, l-[1-13C]leucine, and [13C]urea. A 24-hr urine collection was obtained for determination of [15N]nitrate enrichment (15NO3−) and urinary nitrogen. The next day they received an infusion of l-[5-13C]arginine and l-[5-13C-ureido, 5,5,2H2]citrulline. Blood samples were obtained for determination of plasma isotopic enrichment of the tracers given and of derived [15N]citrulline (nitric oxide synthesis), l-[13C-guanidino 5,5,2H2]arginine (M+3 arg) (arginine synthesis), and [15N2]urea (urea formation). Data are compared with historic controls from studies in healthy young adults.Measurements and Main ResultsPlasma arginine fluxes were 67 ± 21 and 72 ± 17 &mgr;mol·kg−1·hr−1, respectively, for the [15N2guanidino] and the [13C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 ± 10.8 &mgr;mol·kg−1·hr−1and were higher thande novoarginine synthesis rates of 9.6 ± 4.2 &mgr;mol·kg−1·hr−1(p< .01); therefore, these patients were in a negative arginine balance. The rates of nitric oxide synthesis as estimated by the [15N]citrulline method were 1.58 ± 0.69 &mgr;mol·kg−1·hr−1for septic patients and higher (p< .05) than values of 0.96 ± 0.1 &mgr;mol·kg−1·hr−1in healthy adults. Septic patients were in a negative protein (leucine) balance of about −1.00 ± 0.40 g·kg−1·day−1.ConclusionsHomeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereasde novonet arginine synthesis was unchanged, leading to a negative arginine balance. The rates of nitric oxide synthesis and the fraction of plasma arginine used for nitric oxide and urea formation were increased. These findings suggest that under condition of sepsis, arginine becomes essential in critically ill children.