Correlation of Formyl Peptide Receptor 1 With Sepsis-related Encephalopathy: A Prospective Cohort Study

Background The pathogenesis of sepsis-associated encephalopathy (SAE) is unclear, and there are no desired therapeutic methods. Formylpeptide receptor 1 (FPR1) is a cell membrane receptor that recruits leukocytes and mediates inflammatory responses after activation, but its role and mechanism in SAE are unknown. Our previous studies have shown that the expression of FPR1 in the hippocampus of septic mice is increased; FPR1 knockout reduces mortality and microglial activation. Based on this, it is hypothesized that during sepsis, FPR1 induces the migration and recruitment of neutrophils and monocytes to the brain, at the same time, FPR1 activation of microglia mediates brain inflammatory response and cell death, these factors induces or aggravates cognitive dysfunction. This project intends to clarify the relationship between FPR1 activation and SAE from the clinical. The study will provide some useful data for the mechanism study of SAE.

Methods Inclusion criteria for participants were patients with an age of 18-70 years and an inclusion within 24 hours after the beginning of severe sepsis or septic shock according to the criteria that were established by the international guidelines for management of severe sepsis and septic shock.

Patients were excluded from the study if they had a previous diagnosis of a neuropsychiatric disease (head trauma, cerebral stroke, epilepsy, and intracranial infection), current brain disorders (hepatic encephalopathy, pulmonary encephalopathy, and severe electrolyte imbalance), concurrent hematologic diseases, malignant tumor, postcardiac arrest, or melanoma or if they were undergoing cancer chemotherapy.

Demographic, clinical, and laboratory data were retrieved after intensive care unit (ICU) admission from the medical records made by two physicians. Age, gender, Acute Physiology and Chronic Health Evaluation II score (APACHE II score), Sequential Organ Failure Assessment (SOFA) score, GCS score, and infection sites were collected and determined during the first 24 hours of admission. basic laboratory tests, including blood lactate, B-type natriuretic peptide, and inflammatory markers of white blood cell count (WBC), procalcitonin (PCT), and C-reactive protein (CRP), were detected on admission. The GCS and mental status of the patients were evaluated twice a day, at eight o'clock in the morning and six o'clock in the afternoon, including SAE symptoms of somnolence, stupor, coma, confusion, disorientation, agitation, irritability, and decreased level of GCS. Sepsis-associated encephalopathy (SAE) was defined as cerebral dysfunction in the presence of severe sepsis as well as the presentation of two or more of the symptoms listed above after complete withdrawal of sedation.

Original cerebral dysfunction derived from hypoxic encephalopathy, severe hypoglycemia, intracranial hemorrhage, epilepsy relapse, acute ischemic stroke, and hyponatremia were excluded. Supportive treatments, such as the use of a ventilator, length of ICU stay, and 28-day mortality, were also included for assessment.