Arginine and nitric oxide metabolism in critically ill septic pediatric patients

Objective: To investigate whole body, in vivo arginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients. Design: Prospective study. Setting: Pediatric intensive care unit at a general hospital. Patients: Ten consecutive septic patients age 6-16 yrs. Interventions: Septic 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 Results: Plasma arginine fluxes were 67 ± 21 and 72 ±17 μmol·kg^-1·hr^-1 respectively, for the [¹⁵N₂ guanidino] and the [¹³C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 ± 10.8 μmol·kg^-1·hr^-1 and were higher than de novo arginine synthesis rates of 9.6 ± 4.2 μmol·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 μmol·kg^-1·hr^-1 for septic patients and higher (p < .05) than values of 0.96 ± 0.1 μmol·kg^-1·hr^-1 in healthy adults. Septic patients were in a negative protein (leucine) balance of about -1.00 ± 0.40 g·kg^-1·day^-1. Conclusions: Homeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereas de novo net 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.