P0475 - Neuropathological Findings in Pediatric Sepsis Autopsies

Purpose: Sepsis-induced brain injury is associated with an acute deterioration of mental status resulting in cognitive impairment, long-term cognitive deficits, increased functional morbidity, and diminution in the quality of life. The underlying pathophysiology of the septic brain has been suggested to include cerebral edema, blood-brain barrier disruption, microglial activation, increased free radicals, and microvascular injury. In addition to the lack of standard terminology to describe these manifestations, the consequences of sepsis on both acute and chronic neurological outcomes demonstrate a knowledge gap to understand the mechanism involved in sepsis-induced brain injury. As a first step, we retrospectively examined the brain autopsies of pediatric ICU patients to characterize the neuropathological lesions.

Methods: Retrospective chart review of pediatric septic patients who had undergone a neuropathological autopsy from 2008 – 2018 at UPMC Children’s Hospital of Pittsburgh.

Results: Demographics about the 22 septic patients that had an autopsy during the study period are presented in Table 1. Common pre-existing conditions included prematurity (n=6, 27%), immunosuppression secondary to organ transplantation or malignancy (n=5, 23%) and congenital heart disease (n=6, 27%). Approximately 80% of patients had one or more positive cultures identified premortem (Table 1). Almost all of these patients required mechanical ventilation and vasoactive administration for support of multi-organ failure. Extracorporeal membrane oxygenation was used in 41% of the cohort. Pre-mortem imaging was obtained in 17 patients (77%). Abnormal head imaging was found in 25% of head ultrasounds, 85 % head computerized tomography (CT), and all brain magnetic resonance imaging (MRI) scans. CT/MRIs, when performed, demonstrated either an increased ventricle size, global hypoxic injury, or subdural hematoma. EEGs were obtained in 12 patients (55%) with seizures notable in 23% of these patients. The most common autopsy findings were neuronal loss or gliosis (n=8, 36%), infarcts (n=7, 32%) and hypoxic-ischemic encephalopathy (n=6, 27%). Evidence of meningitis/encephalitis was found in only 18% (n=4) (Table 2).

Conclusions: Neuropathological findings are common in autopsies of pediatric septic patients. Understanding the effects of systemic inflammation on the brain during sepsis has the potential to develop targeted therapies to alleviate the pathophysiological manifestations that produce acute consequences such as delirium, and ultimately lead to long-term neurocognitive dysfunction and other functional limitations in survivors.