Editor,—Duke et al report changes in serum markers of nitric oxide (NO) production in children with severe sepsis.¹ Their findings provide additional data concerning activation of the l-arginine-NO pathway during systemic inflammation and also raise some important methodological issues.

The classical serum markers of NO production are nitrite and nitrate; these are also termed reactive nitrogen intermediates (RNls) and are stable and easily measured in body fluids—see review in Feelisch and Stanler.² Levels of these markers in plasma, urine, and saliva are profoundly affected by dietary nitrate, especially ground water³ and nitrate rich food,^{2 4 5} where, after ingestion, levels of nitrate may increase 10-fold in healthy adults.⁶ In order to deplete the body of dietary nitrate and for serum nitrate and nitrite to accurately reflect total body NO production, at least 48 hours of a nitrate free diet is necessary.^{2 4 5}

In this study, Duke and colleagues used unselected emergency admissions of septic patients to an intensive care unit as study subjects, with elective cardiac surgery admissions as controls. It was therefore not …