Chen Yanqing, Huang Xiao, Liu Xiaoli, Tian Huanhuan, Lyu Bingjie, Kong Guiqing, Ning Fangyu, Wang Tao, Hao Dong
Department of Critical Care Medicine, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China. Corresponding author: Hao Dong, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Feb;35(2):146-151. doi: 10.3760/cma.j.cn121430-20220110-00037.
To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis.
A prospective study was conducted. The patients aged ≥ 18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL×kg×h and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days.
Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHE II score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHE II score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×10/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (μg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (μg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (μg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05).
CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.
探讨持续血液净化(CBP)对脓毒症患者免疫功能及内皮细胞功能的影响。
进行一项前瞻性研究。选取2019年3月至2020年10月在滨州医学院附属医院重症医学科住院、年龄≥18岁且符合脓毒症诊断标准的患者作为研究对象,根据随机数字表法将患者分为标准治疗组和CBP治疗组。两组均按照2016年脓毒症和脓毒性休克管理国际指南给予标准治疗,包括初始液体复苏、控制感染源及使用抗生素。CBP治疗组在此基础上,给予持续静脉 - 静脉血液滤过(CVVH),剂量为25 - 30 mL×kg×h,血流速度为150 - 200 mL/min,每天治疗超过20小时,共治疗3天。记录患者治疗前、治疗后1天及3天的临床资料,包括血乳酸(Lac)、降钙素原(PCT)、淋巴细胞计数(LYM)、急性生理与慢性健康状况评分系统II(APACHE II)评分、序贯器官衰竭评估(SOFA)评分。同时采集静脉血,采用酶联免疫吸附测定(ELISA)法检测血清中免疫功能相关指标[白细胞介素(IL - 4、IL - 7)、程序性死亡受体 - 1(PD - 1)、程序性死亡配体 - 1(PD - L1)、干扰素 - γ(IFN - γ)]及内皮细胞损伤相关标志物[可溶性血栓调节蛋白(sTM)、血管生成素 - 2(Ang - 2)、血管性血友病因子(vWF)、硫酸乙酰肝素(HS)、多配体蛋白聚糖 - 1(SDC - 1)]水平。记录两组患者重症监护病房(ICU)住院时间,并对两组患者进行28天随访。
最终,标准治疗组纳入20例患者,CBP治疗组纳入19例患者。两组患者在性别、年龄及感染部位方面无显著差异。标准治疗组ICU住院时间为(10±5)天,28天后5例患者死亡,15例患者存活。CBP治疗组ICU住院时间为(9±4)天,28天后8例患者死亡,11例患者存活。两组患者ICU住院时间及28天内死亡患者数量比较,差异均无统计学意义(均P>0.05)。两组患者治疗前及治疗后1天的Lac、PCT、LYM、APACHE II评分、SOFA评分及免疫功能和内皮细胞损伤相关指标比较,差异均无统计学意义。治疗3天后,CBP治疗组的Lac、PCT、APACHE II评分及SOFA评分均显著低于治疗前,与治疗前相比,促炎和抗炎细胞因子如IFN - γ和IL - 4、凋亡相关指标如PD - 1和IL - 7以及内皮损伤相关因子如sTM、SDC - 1和HS均显著改善,上述指标的改善程度明显优于标准治疗组,LYM显著高于标准治疗组(×10/L:1.3±0.3 vs. 0.9±0.4,P<0.05),IL - 4、IFN - γ、IFN - γ/IL - 4比值、IL - 7、PD - 1、sTM、SDC - 1、HS及Ang - 2均显著低于标准治疗组[IL - 4(ng/L):2.8(1.5,3.2)vs. 3.3(2.7,5.2);IFN - γ(ng/L):6.3(5.4,106.5)vs. 217.9(71.4,517.1);IFN - γ/IL - 4比值:3.7(1.8,70.3)vs. 59.1(18.3,124.9);IL - 7(ng/L):4.6(3.2,5.1)vs. 6.3(5.2,8.0);PD - 1(μg/L):0.04(0.03,0.06)vs. 0.08(0.05,0.12);sTM(μg/L):4.9(4.3,7.4)vs. 8.7(6.0,10.8);SDC - 1(μg/L):0.6(0.3,1.1)vs. 0.9(0.8,2.5);HS(ng/L):434.8(256.2,805.0)vs. 887.9(620.1,957.3);Ang - 2(ng/L):934.0(673.3,1 502.1)vs. 2 233.9(1 472.5,3 808.4)],差异均有统计学意义(均P<0.05)。
CBP治疗可消除患者的免疫抑制状态,降低多种内皮损伤标志物水平及糖萼降解,但不能降低28天死亡风险或缩短ICU住院时间。