Objective: To assess antioxidant protection against iron-catalyzed reactive oxygen species in meningococcal sepsis and to establish whether severity of illness is related to deficiencies in these antioxidant systems.
Design: Prospective, controlled study.
Setting: Pediatric intensive care unit of a postgraduate teaching hospital.
Patients: Twenty children aged 6 months to 15 yrs (median, 5 yrs) with meningococcal septic shock were studied. Paired convalescent samples taken 8-10 wks after discharge were available in nine children.
Interventions: Routine management for meningococcal sepsis.
Measurements and main results: Patients were classified for disease severity using the Glasgow Meningococcal Septicaemia Prognostic Score. Paired acute and convalescent samples were compared. Transferrin level (1.77 +/- 0.08 g/L) and total iron-binding capacity (46.2 +/- 2.0 microM) were significantly decreased in acute patients compared with paired convalescent samples (2.85 +/- 0.10 g/L and 74.4 +/- 2.5 microM, respectively; p <.0001). The iron saturation of transferrin was significantly increased in acute disease (36.9% +/- 2.5%) compared with convalescence (18.8% +/- 1.5%; p =.0003). Iron-binding antioxidant protection was not significantly different in acute (81.4% +/- 1.7%) and paired convalescent samples (85.6% +/- 2.5%; p =.54). However, patients with more severe meningococcal septicemia (GMSPS, >10; n = 12) had significantly diminished protection (77.5% +/- 2.4%) compared with less severe disease (87.1% +/- 1.6%; p =.0028), and there was a significant correlation between disease severity and iron-binding antioxidant protection (R =.48; p =.00067) in acute disease. Paired ceruloplasmin levels were available in six patients and were decreased in acute disease (0.29 +/- 0.02 g/L) compared with convalescence (0.40 +/- 0.04 g/L), although not statistically significant (p =.076). However, there was a significant correlation between plasma ceruloplasmin and disease severity (Pearson product moment correlation, p =.038) in the acute patients. Iron-oxidizing antioxidant assays were performed in four paired samples and were diminished in acute patients (53.3 +/- 4.4%) compared with convalescence (67.8 +/- 3.2%; p =.015). Acute samples demonstrated a significant relationship between iron-oxidizing antioxidant protection and both disease severity (r =.30; p =.012) and plasma ceruloplasmin levels (r =.48; p =.00067).
Conclusions: Children with meningococcal septicemia exhibit abnormal plasma iron chemistry and decreased protection against iron-catalyzed oxidative damage. Such deficiencies correlate with disease severity.