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中华危重症医学杂志(电子版) ›› 2022, Vol. 15 ›› Issue (03) : 189 -197. doi: 10.3877/cma.j.issn.1674-6880.2022.03.003

论著

轻中度感染性疾病患者进展为脓毒症的相关危险因素分析
范致远1, 冯梦晓2, 陆远强1,()   
  1. 1. 310001 杭州,浙江大学医学院附属第一医院急诊科 浙江省增龄与理化损伤性疾病诊治研究重点实验室(范致远为在职研究生,现工作单位为桐乡市第一人民医院急诊科)
    2. 310001 杭州,浙江大学医学院附属第一医院急诊科 浙江省增龄与理化损伤性疾病诊治研究重点实验室
  • 收稿日期:2022-04-12 出版日期:2022-06-30
  • 通信作者: 陆远强
  • 基金资助:
    传染病诊治国家重点实验室开放基金项目(2018KF02); "十三五"浙江省中医药(中西医结合)重点学科(2017-XK-A36)

Risk factors for progression to sepsis in patients with mild to moderate infectious diseases

Zhiyuan Fan1, Mengxiao Feng2, Yuanqiang Lu1,()   

  1. 1. Department of Emergency, Zhejiang Provincial Key Laboratory of Diagnosis and Treatment of Aging and Physical-chemical Injury Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
  • Received:2022-04-12 Published:2022-06-30
  • Corresponding author: Yuanqiang Lu
引用本文:

范致远, 冯梦晓, 陆远强. 轻中度感染性疾病患者进展为脓毒症的相关危险因素分析[J/OL]. 中华危重症医学杂志(电子版), 2022, 15(03): 189-197.

Zhiyuan Fan, Mengxiao Feng, Yuanqiang Lu. Risk factors for progression to sepsis in patients with mild to moderate infectious diseases[J/OL]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2022, 15(03): 189-197.

目的

探讨轻中度感染性患者进展为脓毒症的相关危险因素。

方法

回顾性分析2019年9月至2021年12月收治的390例临床诊断为感染性疾病患者的临床资料。根据入院序贯器官衰竭估计(SOFA)评分将390例患者分为脓毒症组(165例,SOFA评分≥ 2分)和轻中度感染组(225例,SOFA评分<2分)。比较两组患者的一般情况、实验室检查指标及免疫学相关指标。采用Lasso回归模型和多因素Logistic回归模型筛选影响轻中度感染进展为脓毒症的相关影响因素。采用受试者工作特征(ROC)曲线检测各相关因素的预测效能。

结果

与轻中度感染组患者比较,脓毒症患者的年龄较高,起病至就诊时间较短,心率及呼吸较快,心脑血管疾病、糖尿病及高血压病史较多,入院体温、白细胞、中性粒细胞、红细胞分布宽度(RDW)、中性粒细胞与淋巴细胞比值(NLR)、单核细胞与淋巴细胞比值、降钙素原、C反应蛋白、天冬氨酸氨基转移酶、总胆红素、血肌酐、血尿素、乳酸脱氢酶、羟丁酸脱氢酶、肌酸激酶、肌酸激酶同工酶、铁蛋白、乳酸、凝血酶原时间、活化部分凝血活酶时间、D-二聚体、白细胞介素6(IL-6)、IL-10、IL-6/IL-4、IL-6/IL-10均较高,淋巴细胞、单核细胞、血红蛋白、血小板、红细胞压积、胆碱酯酶、白蛋白、血氧饱和度、IL-4、肿瘤坏死因子α(TNF-α)、干扰素γ、TNF-α/IL-10水平均较低(P均<0.05)。经Lasso回归模型及多因素Logistic回归分析显示,RDW[比值比(OR)= 1.399,95%置信区间(CI)(1.122,1.743),P = 0.003]、NLR[OR = 1.050,95%CI(1.010,1.091),P = 0.013]、总胆红素[OR = 1.111,95% CI(1.055,1.170),P<0.001]、血尿素[OR = 1.172,95%CI(1.041,1.320),P = 0.009]及IL-6[OR = 1.006,95%CI(1.002,1.010),P = 0.002]为脓毒症发生的独立危险因素,而血小板[OR = 0.994,95%CI(0.990,0.997),P = 0.001]及白蛋白[OR = 0.866,95%CI(0.799,0.939),P<0.001]则为独立保护因素。ROC曲线分析表明,血小板的曲线下面积(AUC)为0.756[95%CI(0.705,0.808),P<0.001],RDW的AUC为0.748[95%CI(0.699,0.798),P<0.001],NLR的AUC为0.786[95%CI(0.738,0.834),P<0.001],总胆红素的AUC为0.738[95%CI(0.685,0.790),P<0.001],白蛋白的AUC为0.795[95%CI(0.749,0.840),P<0.001],血尿素的AUC为0.780[95%CI(0.729,0.830),P<0.001],IL-6的AUC为0.801[95%CI(0.756,0.845),P<0.001],联合指标的AUC为0.939[95%CI(0.915,0.963),P < 0.001],且联合指标较IL-6(Z = 6.519,P<0.001)、NLR(Z = 6.258,P<0.001)、血尿素(Z = 6.632,P<0.001)、血小板(Z = 7.412,P<0.001)、RDW(Z = 7.631,P<0.001)、白蛋白(Z = 6.164,P< 0.001)及总胆红素(Z = 8.348,P<0.001)单项指标的预测效能更优。

结论

RDW、NLR、总胆红素、血尿素及IL-6为脓毒症发生的独立危险因素,而血小板及白蛋白则为独立保护因素,且联合指标的预测效能相比各独立相关因素更好。

Objective

To investigate the risk factors for progression to sepsis in patients with mild to moderate infectious diseases.

Methods

The clinical data of 390 patients with clinically diagnosed infectious diseases from September 2019 to December 2021 were retrospectively analyzed. According to whether or not sequential organ failure assessment (SOFA) score ≥ 2 on admission, 390 patients were divided into a sepsis group (165 cases) and a mild-moderate infection group (225 cases). The general data, laboratory test indexes, and immunological indexes were compared between the two groups. The Lasso regression model and multivariate Logistic regression model were used to screen the independent factors for influencing the progression of mild-moderate infection to sepsis. The receiver operating characteristic (ROC) curve was used to assess the predictive effectiveness of each correlation factor.

Results

In the sepsis group, the patients were older, the time interval between disease onset and hospital arrival was shorter, the heart rate and respiration were faster, the incidences of cardiovascular and cerebrovascular diseases, diabetes, and hypertension were higher, and the levels of admission temperature, leukocytes, neutrophils, red blood cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio, procalcitonin, C-reactive protein, aspartate aminotransferase, total bilirubin, serum creatinine, blood urea, lactate dehydrogenase, hydroxybutyrate dehydrogenase, creatine kinase, creatine kinase MB, ferritin, lactic acid, prothrombin time, activated partial thromboplastin time, D-dimer, interleukin-6 (IL-6), IL-10, IL-6/IL-4, and IL-6/IL-10 were all much higher than those in the mild-moderate infection group; whereas, the levels of lymphocytes, monocytes, hemoglobin, platelets, hematocrit, cholinesterase, albumin, blood oxygen saturation, IL-4, tumor necrosis factor-alpha (TNF-α), interferon γ, and TNF-α/IL-10 were much lower (all P<0.05). The Lasso regression model and multivariate Logistic regression analysis revealed that the RDW [odds ratio (OR) = 1.399, 95% confidence intervals (CI) (1.122, 1.743), P = 0.003], NLR [OR = 1.050, 95%CI (1.010, 1.091), P = 0.013], total bilirubin [OR = 1.111, 95%CI (1.055, 1.170), P<0.001], blood urea [OR = 1.172, 95%CI (1.041, 1.320), P = 0.009], and IL-6 [OR = 1.006, 95%CI (1.002, 1.010), P = 0.002] were independent risk factors for mild-moderate infection progressing to sepsis, while the platelet [OR = 0.994, 95%CI (0.990, 0.997), P = 0.001] and albumin [OR = 0.866, 95%CI (0.799, 0.939), P<0.001] were independent protective factors. The ROC curve showed that the area under the curve (AUC) of platelets was 0.756 [95%CI (0.705, 0.808), P < 0.001], AUC of RDW was 0.748 [95%CI (0.699, 0.798), P < 0.001], AUC of NLR was 0.786 [95%CI (0.738, 0.834), P < 0.001], AUC of total bilirubin was 0.738 [95%CI (0.685, 0.790), P < 0.001], AUC of albumin was 0.795 [95%CI (0.749, 0.840), P < 0.001], AUC of blood urea was 0.780 [95%CI (0.729, 0.830), P < 0.001], AUC of IL-6 was 0.801 [95%CI (0.756, 0.845), P < 0.001], and AUC of combinated indicator was 0.939 [95%CI (0.915, 0.963), P < 0.001]. The predictive effectiveness of combined indicator model was significantly higher than that of IL-6 (Z = 6.519, P < 0.001), NLR (Z = 6.258, P < 0.001), blood urea (Z = 6.632, P < 0.001), platelet (Z = 7.412, P < 0.001), RDW (Z = 7.631, P < 0.001), albumin (Z = 6.164, P < 0.001), and total bilirubin (Z = 8.348, P < 0.001).

Conclusions

The RDW, NLR, total bilirubin, blood urea, and IL-6 are independent risk factors for mild-moderate infection progressing to sepsis, while the platelet and albumin are independent protective factors. The combined indicator has better predictive efficacy than each independent correlation factor.

表1 两组感染性疾病患者一般情况的比较[MP25P75)]
表2 两组感染性疾病患者实验室指标的比较[MP25P75)]
组别 例数 白细胞(× 109/L) 中性粒细胞(× 109/L) 淋巴细胞(× 109/L) 单核细胞(× 109/L) 血红蛋白(g/L) 血小板(× 109/L) HCT(%) RDW(%) NLR PLR
轻中度感染组 225 7(5,10) 4.7(2.9,7.5) 1.3(0.9,1.8) 0.56(0.43,0.85) 125(111,138) 233(175,298) 37(33,41) 13(12,13) 3.8(2.0,6.3) 177(132,252)
脓毒症组 165 10(6,15) 8.6(5.0,14.0) 0.7(0.4,1.1) 0.53(0.29,0.82) 114.00(94,126) 138(83,213) 33(28,37) 14(13,15) 12.3(5.4,25.1) 214(102,408)
t/χ2/Z   4.830 6.467 9.292 2.085 5.835 8.655 6.105 8.393 9.642 1.578
P   <0.001 <0.001 <0.001 0.037 <0.001 <0.001 <0.001 <0.001 <0.001 0.114
组别 例数 MLR PCT(μg/L) CRP(mg/L) 胆碱酯酶(U/L) ALT(U/L) AST(U/L) 总胆红素(μmol/L) 白蛋白(g/L, ± s 血肌酐(μmol/L) 血尿素(mmol/L) 乳酸脱氢酶(U/L)
轻中度感染组 225 0.48(0.29,0.71) 0.20(0.06,1.29) 62(17,121) 6 194(4 894,7 463) 24(14,50) 22(15,37) 8(6,11) 37 ± 5 72(58,82) 4(3,6) 199(170,258)
脓毒症组 165 0.70(0.39,1.22) 1.90(0.57,11.47) 123(66,195) 3 770(2 803,5 340) 28(16,61) 38(22,84) 15(8,28) 31 ± 5 86(64,142) 8(5,14) 282(219,431)
t/χ2/Z   5.000 8.972 6.724 10.409 1.789 6.617 8.022 11.067 5.748 9.445 8.379
P   <0.001 <0.001 <0.001 <0.001 0.074 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
组别 例数 羟丁酸脱氢酶(U/L) 肌酸激酶(U/L) CK-MB(U/L) 铁蛋白(μg/L) 乳酸(mmol/L) 血氧饱和度(%) PT(s) APTT(s) FBG(g/L) D-二聚体(μg/L)
轻中度感染组 225 153(132,196) 50(34,84) 13(10,16) 445(254,780) 1.20(1.00,1.78) 98(97,98) 12(12,13) 28(26,30) 5.1(3.5,6.50) 960(437,1 959)
脓毒症组 165 221(168,330) 78(37,223) 17(12,28) 738(444,1 831) 1.60(1.10,2.50) 97(95,98) 13(12,15) 31(28,36) 4.7(3.2,6.0) 2 977(1 620,7 772)
t/χ2/Z   8.571 4.472 6.119 7.490 3.475 2.916 6.364 6.704 1.686 9.384
P   <0.001 <0.001 <0.001 <0.001 0.001 0.004 <0.001 <0.001 0.092 <0.001
表3 两组感染性疾病患者免疫学指标的比较[MP25P75)]
图1 Lasso回归变量筛选及交叉验证注:a图显示上横坐标是此时模型中非零系数的个数,图中的每一条曲线代表了每一个自变量系数的变化轨迹,随着λ值(惩罚力度)增加,44个自变量的变量系数不断减少,相对不重要的部分自变量变量系数变为0,因部分变量数字重叠故在图中未显示;b图显示不同的λ值来观察模型误差,上横轴是自变量个数,上图显示有两条虚线,左侧是均方误差最小时的λ值(0.030),对应的变量个数为15个,右侧是距离均方误差最小时一个标准误的λ值(0.053),对应的变量个数为10个,本研究选取右侧虚线构建回归模型
表4 影响轻中度感染患者进展为脓毒症的危险因素分析
图2 ROC曲线分析各影响因素对轻中度感染患者进展为脓毒症的预测效能注:ROC.受试者工作特征;NLR.中性粒细胞与淋巴细胞比值;IL-6.白细胞介素6;RDW.红细胞分布宽度
表5 各指标对轻中度感染患者进展为脓毒症的ROC曲线分析
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