Analysis of the Inflammatory Storm Response and Heparin Binding Protein Levels for the Diagnosis and Prognosis of Sepsis-Associated Encephalopathy
Authors: Yu Dian , Liu Jun , Song Xiaoyun , Ao Yongfeng , Li Xiaomin , Han Yi 
Published: November 2024

Background: Sepsis related encephalopathy(SAE) is a complication that endangers the nervous function during the development of sepsis. Its occurrence is closely related to severe systemic infection. The increase of serum Interleukin 6 and other inflammatory cytokines has certain clinical significance in the diagnosis of sepsis, However, there is no research at home or abroad indicating whether the high expression of related inflammatory cytokines (inflammatory cytokine storm，ICS) is valuable for the diagnosis and prognosis of SAE patients.
Objective: The aim of this study was to analyze serum inflammatory cytokines 6 (IL-2/4/6/10, TNF-α, gamma interferon (IFN-γ)), heparin-binding protein (HBP), serum cholinesterase, and plasma fibrinogen 3 (α2-fibrin inhibitory complex, antithrombin III complex, and fibrinogen TM) levels and their clinical significance in septic patients. In this study, we defined the values of inflammatory storm (IL-6 >5000 pg/ml, IL-10 >1000 pg/ml, and HBP >300 ng/ml) in order to analyze the diagnostic value and 28-day prognostic predictive ability of inflammatory cytokine storm and the severity score in SAE patients
Methods: A total of 140 patients with sepsis in the ICU and EICU of the Lianyungang First People's Hospital were included in the present study from Octobet 2021 to March 2023. Based on the Diagnostic criteria for SAE, the 140 cases were divided into 62 cases in the SAE group and 78 cases in the non-SAE group. On admission to the ICU/EICU, the patients gender, age, vital signs, and serum levels of various cytokines were recorded. The Glasgow Coma Scale (GCS), Sequential Organ Failure Scale (qSOFA), and Acute Physiological and Chronic Health Score II (APACHE-II) scores were also assessed to analyze the risk factors for the occurrence of SAE.
Results: The age, Sofa score, APACHE-II score, 28-day mortality rate, serological cellular inflammatory factors (IL-2/6/10, INF-α, interferon-gamma), HBP, and antithrombin III complex were significantly higher in the SAE group than in the non-SAE group (P<0.05). In addition, the GCS score and serum cholinesterase levels in the SAE group were lower than in the non-SAE group (P< 0.05). Subsequently, multifactorial logistic regression analysis revealed that ultra-high IL-6 (>5000 pg/ml), IL-10 (>1000 pg/ml), and HBP (>300 ng/ml) levels and elevated qSOFA and APACHE-II scores were risk factors for the development of SAE (P<0.05). Moreover, IL-6/10 and HBP indicators positively correlated with qSOFA and APACHE-II scores (P<0.05). 28-day mortality was significantly higher in patients in the SAE group and in the IL-6 >5000 pg/ml group compared to patients in the USAE and IL-6 <5000 pg/ml groups(P<0.001).The four screened predictors of HBP > 300 ng/ml, IL-6 > 5000 pg/ml, decreased GCS score, and decreased APACHEII score were combined into a new predictive data model (risk score).In the SAE group, patients with high risk scores had a higher 28-day mortality rate compared with the low risk score group (p < 0.001)
Conclusion: The occurrence of SAE is closely correlated with age, concomitant diabetes, SOFA score, APACHE II score, serum cytosolic inflammatory factor levels (IL-2/6/10, TNF-α, IFN-γ), HBP, and serum cholinesterase levels. Notably, IL-6 >5000pg/ml, IL-10 >1000pg/ml, and HBP > 300ng/ml are diagnostic indicators of SAE, with IL-6 >5000pg/ml also associated with three severe disease scores and increased 28-day mortality rate (p<0.05), suggesting that inflammatory factor storm levels may be associated with the mechanism of sepsis-associated SAEs and 28-day mortality.According to the LASSO results, when SAE patients admitted to the intensive care unit satisfy HBP > 300ng/ml, IL6 > 5000pg/ml, decreased GCS score, and increased APACHEII score, it suggests that the patient's 28-day mortality rate is higher, and it also validates that inflammatory storm can be used as a predictor of prognosis for SAE patients.