Study On Characteristics Of Early Cytokine Storm In Patients With Septic Shock

Objective: To explore cytokine storm characteristics in patients with septic shock after abdominal surgery,examine its relationship with clinical data,and discuss intervention timings.Methods: We enrolled twenty patients with abdominal infection who were admitted to the surgical intensive care unit after abdominal surgery due to septic shock from April 20,2018 to January 10,2019.Inclusion criteria were septic shock diagnostic criteria in Sepsis 3.0.Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥65 mmHg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation.We excluded patients who had the following criteria: other sources of infection prior to surgery;shock prior to surgery;other types of shock;autoimmune disease;radiotherapy and chemotherapy.We also excluded pregnant women and individuals aged <18 years.In addition,ten healthy individuals of the same race aged between 18 and 90 who had no evidence of autoimmune disease and infection were also enrolled as controls.This study was approved by the Ethics Committee of Dalian Municipal Central Hospital.The registration number of this study is ChiCTR1800014397 in the China Clinical Trial Registry.Both groups received informed consent.The starting point for monitoring cytokine expression was the time of ICU transfer due to septic shock after operation.Blood samples were collected at the five time points of 0,12,24,48 and 72 hour,and clinical data such as general characteristics,hemodynamic parameters,and sequential organ failure assessment(SOFA)scores were recorded.The whole blood samples were collected in a test tube containing ethylenediaminetetraacetic acid(EDTA)for 1 mL.The blood samples were centrifuged for 15 minutes at 1000 ×g and 4 ℃.Subsequently,100 μL plasma was carefully distributed from each sample.The same method was used to extract plasma samples from the control group and one sample was taken from each person.The plasma samples were stored in cryopreservation refrigerator of-80 ℃ for examination,and cytokines were detected every three months.The concentrations of 12 cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-8,IL-10,monocyte chemotactic protein(MCP)-1,IL-1 β,interferon(IFN)-γ,IL-12p70,MCP-1α,IL-4,IL-2,and IL-13 in plasma samples were detected by Luminex technique.The general characteristics of patients included age,sex,procalcitonin measures,lactic acid level,mortality rate,ICU residency period,and surgical operation performed.Hemodynamic data included blood pressure,types and doses of vasopressor,and the vasopressor dependency index.Quantitative data with normal distributions are reported as the mean ± standard deviation.These were compared,using repeated measures analysis of variance,between the shock and control groups.Non-normally distributed quantitative data are presented as the median [interquartile range] and were compared using the Mann-Whitney U test.Part of the general characteristics of the shock group versus the control group were compared by univariate analysis.Differences with a two-tailed p value <0.05 were considered to be statistically significant.Principal component analysis(PCA)was used to determine the weight of 12 cytokines and make the cytokine storm intensity curve.Results: The mean age of the twenty septic shock patients(13 men and 7 women)included in the present study was 75.4 ± 11.4 years,and that of the ten control individuals(5 men and 5 women)was 73.6 ± 12.0 years.There was no significant difference in age and sex between the two groups.There was a significant difference in the cytokine storm intensity between the shock and control group.Almost all levels of the 12 cytokines were significantly higher in the shock group than in the control group at 0,12,and 24 hour.The concentration of IL-6 and MCP-1 was more than 500 pg/ml at 0 hour,and the concentration of IL-6 significant difference between the two groups lasted for more than 72 hour.The cytokine storm intensity curve that we created in this article,vasopressor dependency index,and SOFA score curve in the shock group showed that the time point of maximum intensity of the cytokine storm is earlier than the time point of maximum vasopressor dependency index and maximum SOFA score.Conclusions: Cytokine storm occurred in patients with septic shock shortly after abdominal surgery and may be a main mechanism leading to septic shock.Cytokine storm interventions should ideally be initiated within 24 hour after surgery and be guided by cytokine storm biomarkers.