Objective To study whether the circadian variation of plasminogen-activator-inhibitor-1 (PAI-1) levels, with high morning levels, is associated with poor outcome of children with meningococcal sepsis presenting in the morning hours. Design Retrospective analysis of prospectively collected clinical and laboratory data. Setting Single center study at Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. Subjects 184 patients aged 3 weeks to 18 years with meningococcal sepsis. In 36 of these children, PAI-1 levels at admission to the PICU were measured in plasma by ELISA. Interventions None. Measurements and main results Circadian variation was studied by dividing one day in blocks of 6 hours. Patients admitted between 6:00 am and 12:00 am had increased illness severity scores and higher PAI-1 levels (n = 9, median 6912 ng/mL, IQR 5808-15600) compared to patients admitted at night (P = 0.019, n = 9, median 3546 ng/mL, IQR 1668-6118) or in the afternoon (P = 0.007, n = 7, median 4224 ng/mL, IQR 1804-5790). In 184 patients, analysis of circadian variation in relation to outcome showed more deaths, amputations and need for skin grafts in patients admitted to the PICU between 6:00 am and 12:00 am than patients admitted during the rest of the day (P = 0.009). Conclusions Circadian variation of PAI-1 levels is present in children with meningococcal sepsis and is associated with illness severity, with a peak level in the morning. Whether circadian variation is an independent risk factor for morbidity and mortality in meningococcal sepsis needs to be explored in future studies.

doi.org/10.1371/journal.pone.0167004, hdl.handle.net/1765/94528
Department of Pediatric Surgery

Boeddha, N., Driessen, G., Cnossen, M., Hazelzet, J., & Emonts, M. (2016). Circadian variation of plasminogen-activator-inhibitor-1 levels in children with meningococcal sepsis. PLoS ONE, 11(11). doi:10.1371/journal.pone.0167004