In Vivo Analysis of Tissue S-Nitrosothiols in Pediatric Sepsis

Abstract

S-nitrosothiols are endogenous, bioactive molecules. S-nitrosothiols are implicated in many diseases, including sepsis. It is currently cumbersome to measure S-nitrosothiols clinically. We have previously developed an instrument to measure tissue S-nitrosothiols non-invasively using ultraviolet light. We have performed a prospective case control study of controls and children with sepsis admitted to the PICU. We hypothesized that tissue S-nitrosothiols would be higher in septic patients than controls. Controls were patients with no cardiopulmonary instability. Cases were patients with septic shock. We measured S-nitrosothiols, both at diagnosis and after resolution of shock. A total of 44 patients were enrolled: 21 controls and 23 with sepsis. At baseline, the controls were younger [median age 5 years (IQR 0, 9) versus 11 years (IQR: 6, 16), p-value = 0.012], had fewer comorbidities [7 (33.3%) vs. 20 (87.0%), p-value < 0.001], and had lower PELOD scores [0 (IQR: 0, 0) vs. 12 (IQR: 11, 21), p-value < 0.001]. S-nitrosothiol levels were higher in sepsis cohort (1.1 ppb vs. 0.8 ppb, p = 0.004). Five patients with sepsis had longitudinal measures and had a downtrend after resolution of shock (1.3 ppb vs. 0.9 ppb, p = 0.04). We dichotomized patients based on S-nitrosothiol levels and found an association with worse clinical outcomes, but further work will be needed to validate these findings.

Keywords: S-nitrosothiols; equipment design; pediatric intensive care unit; pediatrics; sepsis.

Figure 1

(A) Photolytic measurement readings obtained at the wrist. Left (dark grey) bar depicts control patients. Right (light grey) bar depicts patients with septic shock. The open square boxes denote the three patients who died. Y-axis is nitric oxide (NO) measured by device in parts per billion. Patients with septic shock had significantly higher levels of NO measured by device when compared to controls (p-value = 0.004). (B) Graphical representation of photolytic measurements obtained during shock (left) and after resolution of shock (right). Photolytic measurements obtained after resolution were statistically significantly lower than the measurements obtained during shock state.

Figure 2

Receiver Operator Characteristic Curve for S-nitrosothiol measurement. Area under the receiver operator characteristic curves are denoted in the bottom left (AUC = 0.7567).