INCREASED SERUM NITRITE AND NITRATE CONCENTRATIONS IN CHILDREN WITH THE SEPSIS SYNDROME

Objectives: To measure total serum nitrite and nitrate concentrations in children with the sepsis syndrome as an indicator of endogenous nitric oxide production. To determine if there is an association between total serum nitrite and nitrate concentrations and vascular responsiveness to norepinephrine. Design: A prospective, clinical study. Setting: Tertiary, multidisciplinary, pediatric intensive care unit. Patients: Thirty-one children with the sepsis syndrome, 18 of whom were also hypotensive. Sixteen critically ill children without signs of the sepsis syndrome served as controls. Interventions: Blood samples were obtained from indwelling catheters. The norepinephrine dose to reach the age appropriate, 50th percentile mean arterial blood pressure was determined in patients receiving norepinephrine. Measurements and Main Results: Total serum nitrite and nitrate concentrations were measured on the first three days after the recognition of the sepsis syndrome. Patients with the sepsis syndrome had increased mean total serum nitrite and nitrate concentrations (day 1, 118 +/- 93 mu M; day 2, 112 +/- 94 mu M; day 3, 112 +/- 93 mu M) vs. controls (43 +/- 24 mu M, P < .05) on all 3 days. When sepsis syndrome patients were separated into nonhypotensive and hypotensive groups, only the patients with hypotension had increased concentrations vs. controls on all three days (p < .05). Sepsis syndrome patients with hypotension also had higher total serum nitrite and nitrate concentrations (145 +/- 97 mu M) than sepsis syndrome patients without hypotension (82 +/- 76 mu M, p < .05) on day 1. In five patients receiving norepinephrine infusions, increased total serum nitrite and nitrate concentrations were associated with higher norepinephrine requirements to maintain an age-appropriate, 50th percentile mean arterial blood pressure on each of the three study days (day 1, r(s) = 0.821,p < .05; day 2, r(s) = 0.900, p < .05; day 3, r(s) = 0.872,p < .05). Conclusions: Children with the sepsis syndrome, particularly those patients with hypotension, have increased total serum nitrite and nitrate concentrations that likely reflect increased endogenous production of nitric oxide. Vascular hyporesponsiveness to norepinephrine during the sepsis syndrome may be, in part, a nitric oxide-mediated process.