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中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (02) : 209 -217. doi: 10.3877/cma.j.issn.1673-5250.2020.02.013

所属专题： 文献；

论著

儿童重症监护病房收治的脓毒症患儿血清乳酸脱氢酶水平对病情及预后的预测价值
杨敏1, 乔莉娜1,†(), 李德渊1, 刘忠强1, 罗黎力1   
  1. 1. 四川大学华西第二医院儿科、出生缺陷与相关妇儿疾病教育部重点实验室，成都　610041
  • 收稿日期:2019-11-18 修回日期:2020-02-08 出版日期:2020-04-01
  • 通信作者: 乔莉娜

Prognostic value of serum lactate dehydrogenase levels in children with sepsis admitted to the pediatric intensive care unit

Min Yang1, Lina Qiao1,†(), Deyuan Li1, Zhongqiang Liu1, Lili Luo1   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2019-11-18 Revised:2020-02-08 Published:2020-04-01
  • Corresponding author: Lina Qiao
  • About author:
    Corresponding author: Qiao Lina, Email:
  • Supported by:
    Sichuan Academic and Technology Leading Training Support Project((2017) 919-23); Project of Science & Technology Department of Sichuan Province(2019YFS0245); Xinya Foundation of West China Second University Hospital, Sichuan University(kx010)
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引用本文：

杨敏, 乔莉娜, 李德渊, 刘忠强, 罗黎力. 儿童重症监护病房收治的脓毒症患儿血清乳酸脱氢酶水平对病情及预后的预测价值[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(02): 209-217.

Min Yang, Lina Qiao, Deyuan Li, Zhongqiang Liu, Lili Luo. Prognostic value of serum lactate dehydrogenase levels in children with sepsis admitted to the pediatric intensive care unit[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(02): 209-217.

目的

探讨脓毒症(sepsis)患儿转入儿童重症监护病房(PICU)24 h内血清乳酸脱氢酶(LDH)水平(以下简称为24 h-LDH水平)，对其疾病程度及预后的预测价值。

方法

收集2015年5月4日至2016年12月31日，于四川大学华西第二医院PICU住院治疗的326例脓毒症患儿为研究对象。回顾性分析其年龄、住院时间、24 h-LDH水平、感染性原发性疾病的受累器官和(或)系统、器官损伤、出院转归等临床病例资料。采用Wilcoxon秩和检验或Kruskal-Wallis H秩和检验，对患儿年龄、住院时间、24 h-LDH水平等进行比较分析。采用Spearman秩相关分析，对24 h-LDH水平分别与脓毒症严重程度、是否发生多器官功能障碍(MODS)和出院转归进行相关性分析。绘制脓毒症患儿24 h-LDH水平预测严重脓毒症、脓毒性休克(SS)、MODS及死亡的受试者工作特征(ROC)曲线，并计算ROC曲线下面积(AUC)，根据约登指数最大原则，确定24 h-LDH水平，对预测严重脓毒症、SS、MODS及死亡的最佳临界值，并计算其预测上述指标的敏感度和特异度。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》的要求。

结果

①脓毒症、严重脓毒症、SS患儿发生MODS发生率分别为27.5%(30/109)、68.8%(121/176)和78.0%(32/41)，死亡率分别为0、8.0%(14/176)和22.0%(9/41)。②脓毒症、严重脓毒症、SS患儿24 h-LDH水平中位数分别为718 U/L(560～976 U/L)，871 U/L(666～1 972 U/L)和1 588 U/L(799～2 150 U/L)，3者比较，差异有统计学意义(χ2＝27.445，P＝0.008)。发生MODS患儿的24 h-LDH水平中位数为713 U/L(571～967 U/L)，显著低于未发生者的1 002 U/L(706～2 150 U/L)，二者比较，差异有统计学意义(Z＝—5.745，P<0.001)。痊愈、好转、放弃和死亡患儿24 h-LDH水平中位数分别为712 U/L(584～945 U/L)、824 U/L(605～1 200 U/L)、1 311 U/L(716～2 150 U/L)和2 150 U/L(1 380～2 150 U/L)，差异亦有统计学意义(χ2＝38.105，P<0.001)。③Spearman秩相关性分析结果显示，24 h-LDH水平分别与脓毒症严重程度、是否发生MODS呈正相关关系(rs＝0.290、0.319，P<0.001)，24 h-LDH水平与脓毒症患儿出院转归呈负相关关系(rs＝ —0.387，P<0.001)。④ROC曲线分析结果显示，24 h-LDH水平预测患儿发生严重脓毒症、SS、MODS及死亡的ROC-AUC分别为0.658(95%CI：0.598～0.719，P<0.001)，0.671(95%CI：0.583～0.759，P<0.001)，0.685(95%CI：0.628～0.742，P<0.001)和0.788(95%CI：0.698～0.879，P<0.001)。根据约登指数最大原则，患儿发生上述4种情况时，血清LDH的最佳临界值分别为1 294.0 U/L、1 307.0 U/L、1 318.5 U/L和1 323.0 U/L(血清LDH水平正常参考值上限为618 U/L)，此时对于预测患儿发生严重脓毒症、脓毒症休克、MODS和死亡的敏感度、特异度分别为39.2%、63.4%、43.7%和82.6%，87.2%、74.7%、78.2%和73.9%。⑤24 h-LDH水平>1 236 U/L的脓毒症患儿的MODS发生率，是24 h-LDH水平≤1 236 U/L者的4.565倍(OR＝4.565，95% CI：2.662～7.830，P<0.001)。⑥患儿出院转归情况为死亡、放弃、好转的与痊愈发生可能性比较，24 h-LDH水平>1 236 U/L患儿，分别较24 h-LDH水平≤1 236 U/L者增高25.175倍(OR＝25.175，95%CI：7.741～81.875，P<0.001)，增高5.979倍(OR＝5.979，95%CI：3.142～11.380，P<0.001)，增高1.619倍(OR＝1.619，95%CI：0.824～3.182，P＝0.162)。

结论

脓毒症患儿24 h-LDH水平与脓毒症严重程度、是否发生MODS及出院转归情况均有关，尤其是24 h-LDH水平>1 236 U/L，可考虑作为预测脓毒症患儿发生MODS风险及判断预后的潜在生物标志物。

关键词: 脓毒症, 重症监护病房，儿科, 乳酸脱氢酶类, 休克，脓毒性, 多器官功能障碍, 转归, ROC曲线, Logistic模型, 儿童
Objective

To investigate the predictive value of serum lactate dehydrogenase (LDH) levels within 24 hours (hereinafter referred to as 24 h-LDH level) on the degree and prognosis of sepsis for the children admitted to the pediatric intensive care unit (PICU).

Methods

A total of 326 children with sepsis who were hospitalized in the PICU of West China Second University Hospital, Sichuan University from May 4, 2015 to December 31, 2016 were collected as research subjects. Clinical data were retrospectively analyzed, including age, hospital stay, 24 h-LDH levels, affected organs /systems of primary infectious disease, organ damage, discharge outcomes, etc.. The Wilcoxon rank sum test or Kruskal-Wallis H rank sum test were used to compare the age, hospital stay, 24 h-LDH levels of children, and so on. Spearman rank correlation analysis was used to analyze the correlation between 24 h-LDH levels, sepsis severity, the occurrence of multiple organ dysfunction (MODS) and discharge outcomes, and so on. The receiver operating characteristic (ROC) curve was drawn to predict severe sepsis, septic shock (SS), MODS and death of children with sepsis by 24 h-LDH levels, and the area under the ROC curve (AUC) was calculated. According to the maximum principle of Youden index, the optimal cut-off value of 24-h LDH levels were determined to predict severe sepsis, SS, MODS and death, and the sensitivity and specificity of the prediction of the above indicators were calculated. This study met the requirements of the World Medical Association Declaration of Helsinki revised in 2013.

Results

①The incidences of MODS in children with sepsis, severe sepsis and SS were 27.5% (30/109), 68.8% (121/176) and 78.0%(32/41), and the mortality rates were 0, 8.0%(14/176) and 22.0% (9/41), respectively. ②The median 24 h-LDH levels of children with sepsis, severe sepsis, and SS were 718 U/L (560-976 U/L) and 871 U/L (666-1 972 U/L) and 1 588 U/L (799-2 150 U/L), respectively, the differences among them was statistically significant (χ2 = 27.445, P=0.008). The median 24 h-LDH levels of sepsis children with MODS was 713 U/L (571-967 U/L), which was significantly lower than that of sepsis patients without MODS 1 002 U/L (706-2 150 U/L), and the difference was statistically significant (Z=—5.745, P<0.001). The median 24 h-LDH levels of children with recovery, improvement, abandonment treatment and death were 712 U/L (584-945 U/L), 824 U/L (605-1 200 U/L), 1 311 U/L (716-2 150 U/L) and 2 150 U/L (1 380-2 150 U/L), respectively, the difference was statistically significant (χ2 =38.105, P<0.001). ③The results of Spearman rank correlation analysis showed that 24 h-LDH levels were positively correlated with sepsis severity and the occurrence of MODS (rs=0.290, 0.319; P<0.001). The level of 24 h-LDH were negatively correlated with the discharge outcomes of children with sepsis (rs=-0.387, P<0.001). ④ROC curve analysis results showed that the ROC-AUC of 24 h-LDH levels predicted severe sepsis, SS, MODS were 0.658 (95%CI: 0.598-0.719, P<0.001), 0.671 (95%CI: 0.583-0.759, P<0.001), 0.685 (95%CI: 0.628-0.742, P<0.001) and 0.788 (95%CI: 0.698-0.879, P<0.001), respectively. According to the maximum principle of the Youden index, when the above four conditions occur, the optimal cutoff values of serum LDH in children were 1 294.0 U/L, 1 307.0 U/L, 1 318.5 U/L, and 1 323.0 U/L (the upper limit of normal reference value of serum LDH level was 618 U/L). And the sensitivity for predicting severe sepsis, septic shock, MODS and death in children were 39.2%, 63.4%, 43.7%, 82.6%, respectively, and the specificity were 87.2%, 74.7%, 78.2% and 73.9%, respectively. ⑤The incidence of MODS in sepsis children with sepsis with 24 h-LDH levels > 1 236 U/L was 4.565 times higher than those with 24 h-LDH levels ≤ 1 236 U/L (OR=4.565, 95%CI: 2.662-7.830, P<0.001). ⑥Compared with the probability of death, abandonment, improvement and complete recovery of patients, the 24 h-LDH levels > 1 236 U/L, which were 25.175 times (OR=25.175, 95%CI: 7.741-81.875, P<0.001), 5.979 times (OR=5.979, 95%CI: 3.142-11.380, P<0.001), 1.619 times (OR=1.619, 95%CI: 0.824-3.182, P=0.162) higher than the 24 h-LDH levels ≤1 236 U/L, respectively.

Conclusions

The 24 h-LDH levels in children with sepsis is related to the severity of sepsis, the occurrence of MODS and discharge outcomes. Especially, the 24 h-LDH levels > 1 236 U/L, which can be considered as a potential biomarker for the prognosis and predicting whether MODS occurs in children with sepsis.

Key words: Sepsis, Intensive care units, pediatric, Lactate dehydrogenases, Shock, septic, Multiple organ dysfunction, Outcome, ROC curve, Logistic models, Child
表1 本组326例脓毒症患儿的一般临床资料
项目 结果 项目 结果
性别[例数(%)] ? 年龄[月，M(P25～P75)] 8(3～25)
? 男 196(60.1) 婴幼儿a [例数(%)] 260(79.8)
? 女 130(39.9) MODS[例数(%)] ?
住院时间[d，M(P25～P75)] 10(4～14) ? 发生 183(56.1)
严重程度[例数(%)] ? ? 未发生 143(43.9)
? 脓毒症 109(33.4) 出院转归情况[例数(%)] ?
? 严重脓毒症 176(54.0) ? 痊愈 126(38.6)
? SS 41(12.6) ? 好转 94(28.8)
原发性感染累及器官和(或)系统[例数(%)] ? ? 放弃 83(25.5)
? 肺 215(66.0) ? 死亡 23(7.1)
? 消化系统 40(12.2) 器官和(或)系统功能损伤[例数(%)] ?
? 神经系统 36(11.0) ? 肺功能 284(87.1)
? 血液循环系统 10(3.1) ? 心功能 118(36.2)
? 泌尿系统 10(3.1) ? 脑神经功能 107(32.8)
? 皮肤软组织 7(2.1) ? 血液系统凝血功能 96(29.4)
? 心脏 3(0.9) ? 肝功能 49(15.0)
? 淋巴结 1(0.3) ? 胃肠道功能 33(10.1)
? 盆腔 1(0.3) ? 肾功能 29(8.9)
? 耳 1(0.3) ? 胰腺功能 1(0.3)
表2 326例不同严重程度与不同出院转归情况脓毒症患儿的24 h-LDH水平比较[U/L，M(P25～P75)]
项目 例数 24 h-LDH水平
脓毒症严重程度 ? ?
? 脓毒症 109 718(560～976)
? 严重脓毒症 176 871(666～1 972)
? SS 41 1 588(799～2 150)
χ2值 ? 27.445
P值 ? 0.008
项目 例数 24 h-LDH水平
MODS ? ?
? 发生 183 713(571～967)
? 未发生 143 1 002(706～2 150)
Z值 ? —5.745
P值 ? <0.001
项目 例数 24 h-LDH水平
出院转归情况 ? ?
? 痊愈 126 712(584～945)
? 好转 94 824(605～1 200)
? 放弃 83 1 311(716～2 150)
? 死亡 23 2 150(1 380～2 150)
χ2值 ? 38.105
P值 ? <0.001
图1 脓毒症患儿24 h-LDH水平预测严重脓毒症、SS、MODS及死亡的的ROC曲线(图1A：严重脓毒症；图1B：SS；图1C：MODS；图1D：死亡)
表3 脓毒症患儿24 h-LDH水平预测严重脓毒症、SS、MODS及死亡的ROC曲线分析结果
指标 ROC曲线 最佳临界值(U/L) 敏感度(%) 特异度(%) 约登指数
ROC-AUC ROC-AUC 95%CI P值
严重脓毒症 0.658 0.598～0.719 <0.001 1 294.0 39.2 87.2 0.259
SS 0.671 0.583～0.759 <0.001 1 307.0 63.4 74.7 0.382
MODS 0.685 0.628～0.742 <0.001 1 318.5 43.7 78.2 0.392
死亡 0.788 0.698～0.879 <0.001 1 323.0 82.6 73.9 0.565
表4 脓毒症患儿24 h-LDH水平对发生MODS及出院转归单因素logistic回归分析赋值
自变量/因变量 变量名 赋值
24 h-LDH水平 y y＝0表示24 h-LDH水平≤1 236 U/L，y＝1表示24 h-LDH水平>1 236 U/L
MODS x1 x1＝0表示患儿未合并MODS，x1＝1表示患儿合并MODS
出院转归 x2 x2＝1表示痊愈，x2＝2表示好转，x2＝3表示放弃，x2＝4表示死亡
表5 脓毒症患儿24 h-LDH水平与其MODS发生率的单因素logistic回归分析
影响因素 Β SE Wald值 P值 OR值 OR值95%CI
24 h-LDH水平a 1.518 0.275 30.430 <0.001 4.565 2.662～7.830
常数项 —2.846 0.498 32.629 <0.001 0.059 —
表6 脓毒症患儿24 h-LDH水平与其出院转归情况的单因素logistic回归分析
影响因素 B SE Wald值 P值 OR值 OR值95%CI
死亡 vs痊愈 ? ? ? ? ? ?
? 24 h-LDH水平 3.277 0.509 41.397 <0.001 25.175 7.741～81.875
? 常数项 —3.227 0.602 28.741 <0.001 — —
放弃vs痊愈 ? ? ? ? ? ?
? 24 h-LDH水平 1.788 0.328 29.667 <0.001 5.979 3.142～11.380
? 常数项 —1.000 0.187 28.503 <0.001 — —
好转 vs痊愈 ? ? ? ? ? ?
? 24 h-LDH水平 0.482 0.345 1.957 0.162 1.619 0.824～3.182
? 常数项 —0.387 0.153 6.414 0.011 — —
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