(892) Neuropathologic Findings in Pediatric Sepsis: A Two-Center Study

Introduction: Sepsis-associated brain dysfunction (SABD) occurs in 20% of pediatric patients and is associated with increased morbidity and mortality. Possible mechanisms include systemic cytokine release, diffuse neuroinflammation, and microglial activation. As limited diagnostic adjuncts and no targeted therapies exist to address SABD, better mechanistic understanding could improve neuroprotective management. We hypothesized that neuroinflammation will be a predominate neuropathological finding in pediatric sepsis.

Methods: We performed a retrospective cohort study of pediatric patients who died from sepsis with neuropathological autopsies at two children’s hospitals (UPMC Children’s Hospital of Pittsburgh (2009 to 2018) and Children’s Hospital of Philadelphia (CHOP; 2011 to 2021)). This study was deemed non-human patient subjects research by CHOP’s Institutional Review Board and UPMC’s Committee for Oversight of Research and Clinical Training Involving Decedents (CORID). Patients less than 6 weeks old were excluded. Demographic, laboratory, neuroimaging, and autopsy data were collected. Categorical data was summarized as frequencies and continuous data as median with interquartile range (IQR).

Results: 61 patients (46 CHOP, 15 UPMC) were included. Median age at death (N = 60) was 27 months [9.4, 117.0]. 49% were female. 84% had a pre-existing condition. Markers of inflammation and end-organ perfusion were elevated (median c-reactive protein 13.4 mg/dL [2.8, 21.9], procalcitonin 31.4 ng/mL [8.6, 70.0], ferritin 2756 ng/mL [381, 15,275], lactate 7.4 mmol/L [2.9, 15.8]). Bacteremia was the most common infectious source (51%). 67% had an EEG during admission, of which 93% had abnormal findings, most commonly diffuse cerebral dysfunction. There was a high level of critical illness: mechanical ventilation (95%), vasoactives (92%), and ECMO (21%). Neuropathological findings included neuronal changes (loss and gliosis, 57%), hypoxic injury (41%), cerebral edema (38%), infectious changes (38%), acute infarcts (13%), and bleeding (20%).

Conclusions: Neuronal changes, hypoxia, and cerebral edema were the most common neuropathological findings. This suggests that limiting neuroinflammation and improving cerebral hemodynamics may be potential neuroprotective measures that can be studied to limit the impact of SABD.