Persistently Higher Serum sCD40L Levels Are Associated With Outcome in Septic Patients

Yingjian Liang; Chengrui Zhu; Yini Sun; Zhiliang Li; Liang Wang; Yina Liu; Xin Li; Xiaochun Ma


BMC Anesthesiol. 2021;21(26) 

In This Article


Design and Subjects

This was a prospective, observational study. Sixty-eight patients who underwent abdominal surgery were enrolled in the Intensive Care Unit of the First Affiliated Hospital, China Medical University from October 1, 2013 to February 28, 2014. These patients included 49 SS and 19 SWS. Six healthy controls were selected. The Ethical Committee of the First Affiliated Hospital of China Medical University approved this study. Because all the patients in our study were admitted to ICU with endotracheal intubation after general anesthesia, these patients were unconscious and unable to sign informed consent due to the influence of sedatives and analgesics. Thus, informed consent forms were signed by the patients' family members (No. 2015–113-2).

Forty-nine SS patients had abdominal infections or pulmonary infections in addition to other sites of infection. Sepsis and septic shock were diagnosed according to the Surviving Sepsis Campaign guidelines committee 2012.[10] The exclusion criteria were age < 18 years, pregnancy, lactation, human immunodeficiency virus (HIV) positive, hematological tumor, immunosuppressed, or undergoing steroid or radiation therapy.

Variables Recorded

In all the patients, age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-related Organ Failure Assessment (SOFA) score, sCD40L, International Society on Thrombosis and Haemostasis (ISTH) score, Japanese Association for Acute Medicine (JAAM) score, platelets, prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, fibrinogen degradation product (FDP), leukocytes, lactate, site of infection, length of stay in the ICU, number of affected organs, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), pressure of arterial oxygen/fraction inspired oxygen (PaO2/FiO2) ratio, sepsis-induced liver injury, invading organisms, and culprit organ with primary sepsis were recorded. Survival at 28 days was used as the study endpoint.

Blood Samples

For patients, blood samples were drawn on days 1, 2 and 3 after ICU admission. For healthy controls, fasting blood samples were obtained at 8:00 am. Serum blood samples were centrifuged at 1500 g for 15 min. The temperature was maintained at 4 °C in all steps after blood collection. Aliquots were stored at − 80 °C for further analysis. Samples were thawed only once. Blood samples from each patient with SS were cultured and analyzed to identify the pathogenic bacteria.

Soluble CD40L Determination

Serum sCD40L concentration was detected by enzyme-linked immunosorbent assays (ELISA) from Life Science, Inc. (China). Each sample was measured in duplicate. The detection limit was 6.1 pg/mL. The intratest variability among the duplicates of all samples was less than 10%.

Statistical Analysis

Continuous variables were analyzed as medians and interquartiles (IQ) 25 and 75% (Q25–Q75), and categorical variables were analyzed as frequencies and percentages. Significant differences in continuous variables between groups were analyzed using the Mann-Whitney U test, and categorical variables were calculated using the chi-square test and Fisher's exact test, as appropriate. Receiver operating characteristic (ROC) curves were used to analyze serum sCD40L levels at days 1, 2 and 3 and establish cut off values. Survival analysis was performed with Kaplan-Meier method curves. Multiple logistic regression analysis was applied to predict 28-day mortality. To determine the association between sCD40L serum levels and other continuous variables at days 1, 2 and 3, Spearman's rank correlation coefficient was used. All P-values < 0.05 were considered statistically significant. SPSS 20.0 (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses.