硬膜外镇痛对产时发热及围产期结局的影响

安红敏，郑伟，谢中，温海燕

硬膜外镇痛对产时发热及围产期结局的影响

安红敏1，郑伟2，谢中1，温海燕1

1.杭州市妇产科医院产科，浙江杭州 310008；2.浙江大学医学院附属儿童医院消化科，浙江杭州 310052

探讨硬膜外镇痛对产时发热及围产期结局的影响。回顾性分析2019年6月1日至6月30日于杭州市妇产科医院分娩的435例产妇的临床资料。根据产妇是否发生产时发热将其分为发热组（=118）和非发热组（=317）。收集产妇的临床资料和实验室检查结果，采用Logistic回归分析探讨产妇硬膜外镇痛合并产时发热的危险因素。两组产妇分娩前后的白细胞（white blood cell，WBC）和C反应蛋白（C-reactive protein，CRP）、胎膜早破（premature rupture of membranes，PROM）≥18h比例及新生儿出生体质量比较，差异均有统计学意义（<0.05）。Logistic回归分析结果显示，新生儿体质量、分娩前CRP、分娩前WBC和PROM≥18h均是产妇硬膜外镇痛合并产时发热的独立危险因素（<0.05）。受试者操作特征曲线结果显示，当硬膜外镇痛时间超过427min时，产妇产时发热的风险显著升高，曲线下面积为0.806，特异性和敏感度分别为72.5%和69.0%。新生儿出生体质量、分娩前CRP、分娩前WBC、PROM≥18h均与硬膜外镇痛合并产时发热有关。持续7h以上的硬膜外镇痛会增加产妇产时发热的风险。

硬膜外镇痛；产时发热；危险因素；产妇结局；新生儿结局

产妇分娩期间出现体温升高的现象称产时发热。产时发热通常体温38.0℃及以上，可由感染性和非感染性因素所致，是新生儿脑病、新生儿窒息、新生儿败血症等围产期不良结局的危险因素之一，发病率3.3%～7.0%[1-5]。产时发热的感染性因素包括绒毛膜羊膜炎和孕妇菌血症[6]；非感染性因素包括硬膜外镇痛、前列腺素诱导分娩、脱水及环境温度升高等[7]。硬膜外镇痛是最常用的分娩镇痛方式。研究发现，20%～30%接受硬膜外镇痛的产妇会经历产时发热[8-10]。硬膜外镇痛相关的产时发热可能是局部麻醉药通过免疫调节和细胞损伤引发的非感染性炎症[11]；也有研究提出与硬膜外镇痛相关的产妇产时发热可能导致不良妊娠结局，并增加新生儿并发症的发生率[12-13]。本研究探讨硬膜外镇痛与产时发热之间的关系及对母婴结局的影响，现将结果报道如下。

1 资料与方法

1.1 研究对象

回顾性分析2019年6月1日至6月30日于杭州市妇产科医院分娩的435例产妇的临床资料。纳入标准：①妊娠37～41周；②单活胎妊娠；③有阴道分娩条件并进入产程试产；④在分娩过程中接受硬膜外镇痛。排除标准：①临床资料不完整；②计划剖宫产；③非单胎妊娠；④死产；⑤胎龄37周之前分娩和先天性胎儿异常的产妇。根据产妇是否发生产时发热将其分为发热组（=118）和非发热组（=317）。本研究经杭州市妇产科医院医学伦理委员会批准（伦理审批号：2023K3-02）。

1.2 硬膜外镇痛方法

当产妇子宫规律收缩且宫颈扩张≥2cm时，给予硬膜外镇痛。产妇左侧卧位，在L2～L3椎间隙进行硬膜外穿刺，并将硬膜外导管插入硬膜外腔4～5cm。镇痛负荷剂量为0.1%罗哌卡因10ml。镇痛设定为2ml/h连续输注，一次应用8ml，暂停15min后继续泵注，最大输注量为35ml。分娩后2h拔除硬膜外导管。

1.3 观察指标

通过查阅电子医疗记录，获得产妇实验室检查结果和产程数据及新生儿结局。产妇的具体指标包括体质量指数（body mass index，BMI）、胎膜早破（premature rupture of membranes，PROM）≥18h、分娩前白细胞（white blood cell，WBC）、分娩前C反应蛋白（C-reactive protein，CRP）、Ⅲ度羊水胎粪污染（meconium-stained amniotic fluid Ⅲ，MSAF Ⅲ）等。新生儿结局包括1分钟Apgar评分和新生儿重症监护病房住院率等。

1.4 统计学方法

2 结果

2.1 两组产妇的一般资料比较

两组产妇分娩前后的WBC和CRP、PROM≥18h比例及新生儿出生体质量比较，差异均有统计学意义（<0.05），见表1。

2.2 产妇硬膜外镇痛合并产时发热的危险因素分析

将新生儿体质量、产妇的分娩前CRP、分娩前WBC、PROM≥18h、分娩后WBC和分娩后CRP纳入进行Logistic回归分析，结果显示新生儿体质量、分娩前CRP、分娩前WBC和PROM≥18h均是产妇硬膜外镇痛合并产时发热的独立危险因素（<0.05），见表2。

表1 两组产妇的一般资料比较

注：PT为凝血酶原时间；APTT为活化部分凝血活酶时间

表2 产妇硬膜外镇痛合并产时发热的危险因素分析

2.3 硬膜外镇痛持续时间与产时发热的关系

通过受试者操作特征曲线（receiver operating characteristic curve，ROC曲线）分析确定硬膜外镇痛持续时间的理想临界值。结果表明，硬膜外镇痛时间能很好地预测产时发热，曲线下面积为0.806，阈值为427min，特异性和敏感度分别为72.5%和69.0%，见图1。

图1 硬膜外镇痛持续时间与产时发热的ROC曲线

3 讨论

1989年，Fusi首次提出产妇硬膜外镇痛与产时发热密切相关，之后硬膜外镇痛引起产科医生和麻醉师的广泛兴趣[14]。产妇产时发热与硬膜外镇痛的发病机制一直存在争议[10]。既往研究表明，非感染性炎症可能发挥潜在作用[15-16]。Riley等[17]比较分娩过程中接受硬膜外镇痛与未接受硬膜外镇痛的产妇的胎盘感染率，发现虽然两组产妇的胎盘感染率相似，但接受硬膜外镇痛的产妇更有可能经历产时发热。Sultan等[9]指出，硬膜外镇痛引起的发热可能是炎症反应驱动的结果，潜在的炎症因素包括硬膜外置管、分娩和局部麻醉药的创伤。一项双盲、安慰剂对照研究结果显示，在硬膜外麻醉前给予产妇抗生素，并未降低产妇产时发热及胎盘炎症的发生率，该研究结果证实与硬膜外镇痛相关的产妇发热是一种非感染性炎症[18]。硬膜外镇痛通过阻断交感神经和引起高于镇痛水平的血管收缩以减少热损失，同时减轻疼痛、骨骼肌活动和呼吸频率，并提高出汗阈值，进而使体温调节中枢发生进一步的生物学变化，导致体温升高[19]。本研究显示硬膜外镇痛合并产时发热产妇的分娩前后WBC和CRP及PROM≥18h比例均明显高于无产时发热产妇，提示硬膜外镇痛合并产时发热的情况下，要警惕感染因素存在。

Dior等[4]发现硬膜外镇痛与产妇产时发热有关，而产妇产时发热是产科常见不良结局的重要危险因素，如产后出血、难产等。Sharpe等[10]认为发热对新生儿的影响包括神经抑制症状，如Apgar评分降低和心肺复苏增加；Törnell等[20]发现硬膜外镇痛与新生儿神经系统预后不良无关，仅与新生儿Apgar评分下降有关；Zheng等[21]研究发现与在第二产程终止镇痛相比，在第二产程持续硬膜外镇痛不影响母胎结局。本研究结果显示硬膜外镇痛合并产时发热与新生儿出生体质量、分娩前WBC、分娩前CRP和PROM≥18h均有关。提示产妇若存在分娩前WBC和CRP明显高于正常及PROM≥18h，给予硬膜外镇痛时要监测体温，警惕产时发热的发生。进一步的ROC曲线分析显示，硬膜外镇痛持续时间超过427min（约7h）可显著增加产妇产时发热的风险。提示医护人员在整个分娩过程中监测产妇体温是非常重要和必要的，特别是硬膜外镇痛时间超过7h，应及早采取预防产妇产时发热的措施，如降低室温、减少衣物、补水、使用催产素加速分娩等。

综上所述，新生儿出生体质量、产妇的分娩前WBC、分娩前CRP和PROM≥18h均是硬膜外镇痛合并产时发热的独立危险因素。超过7h的硬膜外镇痛可增加产妇产时发热的风险。

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Effect of epidural analgesia on intrapartum fever and perinatal outcomes

AN Hongmin, ZHENG Wei, XIE Zhong, WEN Haiyan

1.Department of Obstetrics, Hangzhou Women’s Hospital, Hangzhou 310008, Zhejiang, China; 2.Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang, China

ObjectiveTo investigate the effect of epidural analgesia on intrapartum fever and perinatal outcomes.Methods The clinical data of 435 pregnant women delivered at Hangzhou Women’s Hospital from 1 June to 30 June 2019 were retrospectively analysed. Pregnant women were divided into febrile group (=118) and non-febrile group (=317) according to whether they were febrile at delivery. The clinical data and laboratory findings were collected, and Logistic regression analysis was used to evaluate the risk factors of epidural analgesia combined with intrapartum fever. Results White blood cell (WBC) and C-reactive protein (CRP) before and after delivery, proportion of premature rupture of membranes (PROM) ≥18h and neonatal birth weight between the two groups showed statistically significant differences (<0.05). Logistic regression analysis showed that neonatal birth weight, pre-delivery CRP, pre-delivery WBC and PROM≥18h were independent risk factors for epidural analgesia combined with intrapartum fever (<0.05). The results of receiver operating characteristic curve showed that the risk of intrapartum fever was significantly higher, when the duration of epidural analgesia exceeded 427 min, with an area under the curve of 0.806 and specificity and sensitivity of 72.5% and 69.0%, respectively. Conclusion Neonatal birth weight, pre-delivery CRP, pre-delivery WBC and PROM≥18h were all associated with epidural analgesia combined with intrapartum fever. Epidural analgesia lasting longer than 7 hours increases the risk of intrapartum fever.

Epidural analgesia; Intrapartum fever; Risk factor; Maternal outcome; Neonatal outcome

R714

A

10.3969/j.issn.1673-9701.2023.22.001

浙江省卫生健康科技计划项目（2022KY869）

温海燕，电子信箱：wenhy1991@163.com

（2023–02–17）

（2023–07–14）