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 methemoglobin and nitrite/nitrate concentrations and to compare these markers of nitric oxide overproduction with clinical variables in children diagnosed with septic shock.

DESIGN

Prospective, controlled, clinical study.

SETTING

Pediatric intensive care unit and outpatient clinic in a children's hospital.

PATIENTS

Twenty-two children diagnosed with septic shock and ten age-matched healthy control patients.

INTERVENTIONS

Patients diagnosed with septic shock had blood specimens taken on study entry and every 6 hrs for 72 hrs for methemoglobin and nitrite/nitrate determinations. Single blood specimens were obtained from controls.

MEASUREMENTS AND MAIN RESULTS

Circulating methemoglobin and nitrite/nitrate 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 correlated with serum creatinine (r2 = .19; p = .04) and were inversely correlated with arterial pH (r2 = .28; p = .01) and urine output (r2 = .21; p = .03) when analyzed by log-linear regression. There were no significant relationships between methemoglobin and nitrite/nitrate or between methemoglobin and any other clinical variable.

CONCLUSIONS

Circulating methemoglobin and nitrite/nitrate concentrations are increased in children diagnosed with septic shock. Plasma nitrite/nitrate values correlate with selected clinical variables in these children. Circulating methemoglobin measurements are not superior to plasma nitrite/nitrate concentrations as an indicator of endogenous overproduction of nitric oxide in children diagnosed with septic shock. A need remains to develop markers of endogenous nitric oxide activity that have greater accuracy and reliability.