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中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (05) : 543 -550. doi: 10.3877/cma.j.issn.1673-5250.2020.05.007

所属专题： 文献；

论著

早期目标导向治疗后检测乳酸清除率对连续性血液净化治疗脓毒性休克患儿时机选择的指导作用
谢友军1,†(), 莫武桂1, 韦跃1, 韦蓉1, 唐育鹏1   
  1. 1. 广西壮族自治区妇幼保健院重症医学科，南宁　530003
  • 收稿日期:2020-04-02 修回日期:2020-09-15 出版日期:2020-10-01
  • 通信作者: 谢友军

Guiding effect of lactic acid clearance rate detection after early goal-directed therapy on timing selection of continuous blood purification for septic shock in children

Youjun Xie1,†(), Wugui Mo1, Yue Wei1, Rong Wei1, Yupeng Tang1   

  1. 1. Department of Critical Care Medicine, Maternity and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, Guangxi Zhuang Autonomous Region, China
  • Received:2020-04-02 Revised:2020-09-15 Published:2020-10-01
  • Corresponding author: Youjun Xie
  • Supported by:
    Self-Financing Project of Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(Z20170786)
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引用本文：

谢友军, 莫武桂, 韦跃, 韦蓉, 唐育鹏. 早期目标导向治疗后检测乳酸清除率对连续性血液净化治疗脓毒性休克患儿时机选择的指导作用[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(05): 543-550.

Youjun Xie, Wugui Mo, Yue Wei, Rong Wei, Yupeng Tang. Guiding effect of lactic acid clearance rate detection after early goal-directed therapy on timing selection of continuous blood purification for septic shock in children[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(05): 543-550.

目的

探讨接受早期目标导向治疗(EGDT)方案后，检测脓毒性休克(SS)患儿乳酸清除率，对其进一步采取连续性血液净化治疗(CBP)时机选择的指导作用。

方法

选取2017年1月至2019年12月，广西壮族自治区妇幼保健院新阳、厢竹院区儿童重症监护病房(PICU)收治的接受EGDT方案后，乳酸清除率<10%，并且符合本研究纳入与排除标准的36例SS患儿为研究对象。采用信封法，将其随机分为研究组(n＝21，立即进行CBP治疗)与对照组(n＝15，先进行集束化治疗，若患儿器官功能进行性恶化，再进行CBP治疗)。采集2组患儿的一般临床资料，入院时(d0)、入院后第3天(d3)、入院后第5天(d5)血浆白细胞介素(IL)-6、10与肿瘤坏死因子(TNF)-α水平，以及血浆乳酸浓度达标时间、尿量达标时间、CBP治疗时间、机械通气时间、PICU住院时间，并采用重复测量资料的方差分析，或成组t检验进行统计学比较。2组患儿性别、年龄与原发感染部位构成比及治疗前血浆乳酸浓度、小儿危重病例评分(PCIS)等临床资料分别比较，差异均无统计学意义(P>0.05)。本研究遵循的程序符合广西壮族自治区妇幼保健院伦理委员会所制定的医学伦理学标准，并得到该委员会审批[审批文号：(2017-1)4-16号]。本研究与纳入研究患儿监护人均签署临床研究知情同意书。

结果

①2组患儿d0、d3、d5血浆IL-6、IL-10、TNF-α水平，经重复测量资料的方差分析结果显示，对于血浆IL-6、IL-10水平，不同处理措施与时间因素有交互效应(F处理×时间＝14.937、P<0.001，F处理×时间＝5.314、P<0.001)，而对于血浆TNF-α水平，不同处理措施与时间因素无交互效应(F处理×时间＝2.918、P＝0.092)。进一步固定时间因素进行分析的结果显示，研究组患儿d3血浆IL-6、IL-10、TNF-α水平，均显著低于对照组，并且差异均有统计学意义(t＝-4.957、P<0.001, t＝-6.545、P<0.001，t＝-2.638、P＝0.012)。进一步固定处理措施因素进行分析的结果显示，研究组、对照组患儿血浆IL-6、IL-10、TNF-α水平均呈进行性下降趋势，组内不同时间血浆IL-6、IL-10、TNF-α水平两两比较，除研究组患儿d3与d5血浆TNF-α水平比较，差异无统计学意义(P>0.05)，其余指标比较，差异均有统计学意义(P<0.05)。②研究组患儿血浆乳酸浓度达标时间、尿量达标时间、CBP治疗时间、机械通气时间、PICU住院时间分别为(4.7±1.2)d、(4.3±1.5)d、(3.4±1.2)d、(7.1±1.7)d、(10.1±2.4)d，均显著短于对照组的(6.3±1.4)d、(5.4±1.3)d、(4.3±1.1)d、(8.4±1.8)d、(12.8±2.5)d，2组分别比较，差异均有统计学意义(t＝3.648、2.192、2.397、2.173、3.294，P＝0.001、0.035、0.022、0.037、0.002)。

结论

SS患儿接受EGDT方案后，对其中乳酸清除率<10%者早期进行CBP治疗，可快速降低患儿炎症反应强度，控制病情，缩短病程。由于本研究纳入样本量相对较小，SS患儿接受EGDT方案后，乳酸清除率对SS患儿进一步采取CBP治疗的时机选择指导作用，仍需多中心、大样本、随机对照试验进一步证实。

关键词: 休克, 脓毒性, 血液透析滤过, 乳酸, 白细胞介素6, 白细胞介素10, 肿瘤坏死因子α, 早期目标导向治疗, 乳酸清除率, 连续性血液净化, 儿童
Objective

To explore guiding effect of lactic acid clearance rate detection of children with septic shock (SS) after receiving early goal-directed therapy (EGDT) on timing selection of further receiving continuous blood purification (CBP).

Methods

From January 2017 to December 2019, a total of 36 children with SS admitted to pediatric intensive care unit (PICU) in Maternity and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as research subjects, with lactic acid clearance rate<10% after receiving EGDT and meeting the inclusion and exclusion criteria of this study. The children with SS were randomly divided into study group (n=21) and control group (n=15) by envelope method. They were treated with early CBP, or first treated with cluster therapy, and then treated with CBP if their organ functions showed progressive deterioration, respectively. General clinical data, plasma levels of interleukin (IL)-6, 10 and tumor necrosis factor (TNF)-α on admission (d0), 3 days after admission (d3), and 5 days after admission (d5), and duration of plasma lactic acid concentration up to standard level, duration of urine volume up to standard level, CBP treatment time, mechanical ventilation time, and hospital stay in PICU of two groups were collected. ANOVA of repeated measurement data and independent-samples t test were used for statistical comparisons. There were no statistical differences between two groups in general clinical data, such as composition ratios of gender, age and primary infection locations, plasma lactic acid concentration before treatment, and pediatric critical illness score (PCIS) (P>0.05). The procedure followed in this study conformed to the standards of medical ethics in Maternity and Child Health Care Hospital of Guangxi Zhuang Autonomous Region and has been approved by this ethics committee [approval No. (2017-1)4-16]. All guardians of children have signed informed consent of clinical research.

Results

①ANOVA of repeated measurement data results of plasma IL-6, IL-10 and TNF-α levels on d0, d3 and d3 showed that as for plasma levels of IL-6 and IL-10, the interaction between different treatment measures and time factors was statistically significant (Ftreatment×time=14.937, P<0.001; Ftreatment×time=5.314, P<0.001), while as for plasma level of TNF-α, the interaction between different treatment measures and time factors was not statistically significant (Ftreatment×time=2.918, P=0.092). Results of further analysis by fixing time factor showed that plasma levels of IL-6, IL-10 and TNF-α on d3 in study group were significantly lower than those in control group, and all differences were statistically significant (t=-4.957, P<0.001; t=-6.545, P<0.001; t=-2.638, P=0.012). Results of further analysis by fixing factor of treatment measures showed that plasma levels of IL-6, IL-10 and TNF-α in study group and control group showed a progressive decrease trend, and there were statistical differences in further comparisons between different times within each group (P<0.05) except for the comparison of d3 and d5 plasma levels of TNF-α in study group. ②Duration of plasma lactic acid concentration up to standard level, duration of urine volume up to standard level, CBP treatment time, mechanical ventilation time, and hospital stay in PICU of children in study group were (4.7±1.2) d, (4.3±1.5) d, (3.4±1.2) d, (7.1±1.7) d, (10.1±2.4) d, respectively, which were significantly shorter than those in control group (6.3±1.4) d, (5.4±1.3) d, (4.3±1.1) d, (8.4±1.8) d, (12.8±2.5) d, and all differences were statistically significant (t=3.648, 2.192, 2.397, 2.173, 3.294, P=0.001, 0.035, 0.022, 0.037, 0.002).

Conclusions

Early CBP treatment for SS children with lactic acid clearance rate<10% after receiving EGDT can rapidly reduce intensity of inflammatory response, control the disease, and shorten course of disease. Due to relatively small sample size included in this study, guiding effect of lactic acid clearance rate after receiving EGDT on timing selection of CBP for children with SS still needs to be further confirmed by multi-center, large-sample, randomized controlled trials.

Key words: Shock, septic, Hemodiafiltration, Lactic acid, Interleukin-6, Interleukin-10, Tumor necrosis factor-alpha, Early goal-directed therapy, Lactic acid clearance rate, Continuous blood purification, Child
表1 2组脓毒性休克患儿临床资料比较
组别 例数 性别[例数(%)] 年龄[例数(%)] 治疗前血浆乳酸浓度(mmol/L，±s)
男 女 <1岁 1～3岁 >3岁
研究组 21 12(57.1) 9(42.9) 9(42.9) 6(28.6) 6(28.6) 5.4±1.6
对照组 15 8(53.3) 7(46.7) 7(46.7) 5(33.3) 3(20.0) 5.1±2.1
检验值   χ2＝0.051 χ2＝0.351 t＝0.488
P值   0.821 0.839 0.629
组别 例数 原发感染部位[例数(%)] 治疗前PCIS(分，±s)
肺部 肠道及腹腔 血流 中枢神经系统 其他部位
研究组 21 6(28.6) 5(23.8) 5(23.8) 2(9.5) 3(14.3) 66.4±7.2
对照组 15 5(33.3) 3(20.0) 4(26.7) 2(13.3) 1(6.7) 69.5±7.3
检验值   χ2＝0.722 t＝-1.278
P值   0.949 0.210
表2 2组脓毒性休克患儿不同时间炎症指标比较(pg/mL，±s)
组别 例数 血浆IL-6水平 血浆IL-10水平 血浆TNF-α水平
d0 d3 d5 d0 d3 d5 d0 d3 d5
研究组 21 425±141 134±56 69±27 151±58 25±11 17±8 54±17 16±7 16±9
对照组 15 412±165 284±107 83±44 140±54 54±15 19±11 60±22 24±11 15±8
F处理×时间值   14.937 5.314 2.918
P值   <0.001 0.027 0.092
F处理值   3.042 0.571 1.294
P值   0.090 0.454 0.264
F时间值   232.365 233.391 283.812
P值   <0.001 <0.001 <0.001
表3 2组脓毒性休克患儿预后相关指标比较(d，±s)
组别 例数 血浆乳酸浓度达标时间 尿量达标时间 CBP治疗时间 机械通气时间 PICU住院时间
研究组 21 4.7±1.2 4.3±1.5 3.4±1.2 7.1±1.7 10.1±2.4
对照组 15 6.3±1.4 5.4±1.3 4.3±1.1 8.4±1.8 12.8±2.5
t值   3.648 2.192 2.397 2.173 3.294
P值   0.001 0.035 0.022 0.037 0.002
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