中性粒细胞CD64与白细胞介素-6和降钙素原对ICU脓毒症患者的诊断及预后评估

Diagnostic and prognostic value of neutrophil CD64,IL-6,and PCT in ICU patients with sepsis

目的探讨中性粒细胞CD64(nCD64)、白细胞介素-6(IL-6)和降钙素原(PCT)单独及联合应用在脓毒症患者诊断及预后评估中的意义。方法采用前瞻性研究方法,选取2020年9月至2021年10月入住青岛大学附属烟台毓璜顶医院西区重症监护病房(ICU)的成人患者为研究对象,于入ICU 6 h内采集外周血测定nCD64、IL-6、PCT水平,脓毒症患者在入ICU后3 d和7 d再次测量nCD64、IL-6、PCT水平。根据脓毒症3.0诊断标准,将纳入患者分为脓毒症组和非脓毒症组,明确nCD64、IL-6和PCT对脓毒症的诊断价值;根据入ICU时的病情,将脓毒症患者分为脓毒症组和脓毒性休克组,判断3种生物标志物对脓毒症病情的评估价值;根据28 d生存情况将脓毒症患者分为存活组和死亡组,评估3种生物标志物与脓毒症预后的关系。结果最终纳入脓毒症患者47例,脓毒性休克患者43例,非脓毒症患者41例。脓毒症患者28 d存活76例,死亡14例。①脓毒症组入ICU后1 d的nCD64、IL-6、PCT均明显高于非脓毒症组〔nCD64:26.95(14.05,86.18)比3.10(2.55,5.10),IL-6(ng/L):93.45(52.73,246.30)比34.00(9.76,62.75),PCT(μg/L):6.63(0.57,68.50)比0.16(0.08,0.35),均P<0.01〕。受试者工作特征曲线(ROC曲线)分析显示,nCD64、IL-6、PCT单独诊断脓毒症的曲线下面积(AUC)分别为0.945、0.792、0.888,以nCD64的诊断价值最高,当nCD64最佳截断值为7.45时,其敏感度为92.2%,特异度为95.1%。将nCD64、IL-6、PCT两两及三者联合诊断时,三者联合的诊断性能最高,AUC达0.973,敏感度为92.2%,特异度为97.6%。②脓毒性休克组入ICU后1、3、7 d的nCD64、IL-6、PCT水平均高于脓毒症组。ROC曲线分析显示,入ICU后1、3、7 d的nCD64、IL-6、PCT用于评估脓毒症病情有一定的准确性,AUC在0.682~0.777。③死亡组nCD64、IL-6、PCT水平均高于存活组,除入ICU后1 d的nCD64、PCT值外,其余时间点各指标两组差异均有统计学意义。ROC曲线分析显示,各时间点nCD64、IL-6、PCT预测脓毒症预后的AUC在0.600~0.981。用nCD64、IL-6、PCT入ICU后1 d与3 d或7 d的差值除以1 d时的数值计算其入ICU后3 d和7 d的清除率,用Logistic回归分析其对脓毒症预后的预测价值,结果显示,除7 d的IL-6清除率无意义外,入ICU后3 d和7 d的nCD64、IL-6、PCT清除率均是脓毒症患者28 d死亡的保护因素。结论nCD64、IL-6、PCT作为诊断脓毒症的生物标志物有较好的价值,nCD64的诊断价值高于PCT和IL-6,当三者联合应用时诊断价值最高。nCD64、IL-6、PCT在评估脓毒症患者病情程度及预测预后上有一定的价值,nCD64、IL-6、PCT的清除率越高,脓毒症患者28 d死亡风险就越小。

Objective To explore the significance of neutrophil CD64(nCD64),interleukin-6(IL-6),and procalcitonin(PCT)alone and in combination in the diagnosis and prognosis evaluation of patients with sepsis.Methods A prospective study was conducted.Adult patients admitted to the Western Intensive Care Unit(ICU)of Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University from September 2020 to October 2021 were selected as subjects.The venous blood of the selected patients was collected within 6 hours of entering the ICU to measure the levels of nCD64,IL-6 and PCT.The levels of nCD64,IL-6 and PCT of septic patients were measured again on the 3rd and 7th days after admission to ICU.According to the diagnostic criteria of Sepsis-3,the patients were divided into sepsis group and non-sepsis group to evaluate the diagnostic value of nCD64,IL-6 and PCT in sepsis.The patients with sepsis were divided into sepsis group and septic shock group according to their condition on admission to ICU,and the evaluation value of three biomarkers for sepsis was evaluated.Sepsis patients were divided into the survival group and the death group according to survival after 28 days,and the relationship between the three biomarkers and the prognosis of sepsis was evaluated.Results Finally,47 patients with sepsis,43 patients with septic shock,and 41 patients without sepsis were enrolled.Seventy-six patients with sepsis survived and 14 died after 28 days.①The levels of nCD64,IL-6 and PCT on the first day of ICU admission in the sepsis group were significantly higher than those in the non-sepsis group[nCD64:26.95(14.05,86.18)vs.3.10(2.55,5.10),IL-6(ng/L):93.45(52.73,246.30)vs.34.00(9.76,62.75),PCT(μg/L):6.63(0.57,68.50)vs.0.16(0.08,0.35),all P<0.01].The receiver operator characteristic curve(ROC curve)showed that the area under curve(AUC)of nCD64,IL-6 and PCT in the diagnosis of sepsis were 0.945,0.792 and 0.888,respectively.The diagnostic value of nCD64 was the highest.When the cut-off value of nCD64 was 7.45,the sensitivity and specificity were 92.2%and 95.1%respectively.When nCD64,IL-6 and PCT were diagnosed in pairs or in combination,the combination of the three had the highest diagnostic performance,with AUC of 0.973,sensitivity of 92.2%and specificity of 97.6%.②The levels of nCD64,IL-6 and PCT in septic shock group were higher than those in sepsis group on the 1st,3rd and 7th day after admission to ICU.ROC curve analysis showed that nCD64,IL-6 and PCT had some accuracy in evaluating the severity of sepsis on the 1st,3rd and 7th day after entering ICU,with AUC ranging from 0.682 to 0.777.③The levels of nCD64,IL-6 and PCT in the death group were significantly higher than those in the survival group.Except for the nCD64 and PCT values on the first day after admission to the ICU,there were significant differences between the two groups in all indicators at other time points.ROC curve analysis showed that the AUC of nCD64,IL-6 and PCT predicting the prognosis of sepsis at each time point ranged from 0.600 to 0.981.The clearance rates of nCD64,IL-6 and PCT at 3 and 7 days after ICU admission were calculated by dividing the difference between the 1st and 3rd or 7th days after entering the ICU by the value at the 1st day.Logistic regression was used to analyze their predictive value for the prognosis of sepsis.The results showed that the clearance rates of nCD64,IL-6 and PCT on the 3rd and 7th day of ICU were protective factors for 28-day mortality in patients with sepsis,except the clearance rate of IL-6 on the 7th day.Conclusions nCD64,IL-6 and PCT have good value as biomarkers for the diagnosis of sepsis.The diagnostic value of nCD64 is higher than that of PCT and IL-6.When they are used together,the diagnostic value is the highest.nCD64,IL-6 and PCT have certain value in evaluating the severity and predicting the prognosis of patients with sepsis.The higher the clearance rate of nCD64,IL-6 and PCT,the lower the 28-day mortality risk of patients with sepsis.