Neuropathologic Autopsy Findings in Pediatric Sepsis: A Two-Center, Retrospective Study

Objectives: – During sepsis, acute brain dysfunction is associated with death and morbidity. However, there are limited data on the pathophysiology of sepsis brain dysfunction. Design: – Retrospective cohort study. Setting: – Two quaternary free-standing children’s hospitals (University of Pittsburgh Medical Center [UPMC] Children’s Hospital of Pittsburgh and Children’s Hospital of Philadelphia [CHOP]). Subjects: – Sepsis patients with a neuropathological autopsy from 2009 to 2018 at UPMC and 2011–2021 at CHOP. Interventions: – None. Measurements and Main Results: – We identified 57 patients with a median (interquartile range [IQR]) age at admission of 34.5 months (IQR, 9.2–118.0 mo). Overall, 48 of 57 (84%) patients had preexisting comorbidity including: metabolic/genetic disorders (19/57, 33%), immunocompromise (12/57, 21%), and prematurity (12/57, 21%). Almost all patients required inotropes (53/57, 93%) or invasive mechanical ventilation (54/57, 95%). Forty-four percent of patients (25/57) had a cardiac arrest either before or during admission. Almost half of patients had multisite infections (25/57, 44%), with 23 of 25 having a component of bacteremia and four of 25 having a CNS infection. Gross neuropathological findings included edema in 39% (22/57), ventriculomegaly in 39% (22/57), and hemorrhage in 30% (17/57). Microscopic CNS examination results were available for 51 of 57 patients (89%) and the acute/subacute microscopic findings included: neuronal injury in 45% (23/51), acute infarction in 25% (13/51), and white matter necrosis in 25% (13/51). Most patients (49/57, 86%) had at least one acute gross or microscopic finding. In univariate analyses, premortem CNS infections, was associated with edema (p = 0.001). Also, absence of comorbidities was associated with gross edema (p = 0.009) and microscopic acute neuronal injury (p = 0.008), acute infarction (p = 0.01), and meningitis (p = 0.004). Conclusions: – In our retrospective neuropathological study of sepsis cases, we found that pathologies were common. While correlations to sepsis survivors cannot be determined, further studies are needed to develop strategies that prevent and treat neuropathological injury.