安紅敏，鄭偉，謝中，溫海燕

硬膜外鎮(zhèn)痛對產(chǎn)時發(fā)熱及圍產(chǎn)期結(jié)局的影響

安紅敏1，鄭偉2，謝中1，溫海燕1

1.杭州市婦產(chǎn)科醫(yī)院產(chǎn)科，浙江杭州 310008；2.浙江大學(xué)醫(yī)學(xué)院附屬兒童醫(yī)院消化科，浙江杭州 310052

探討硬膜外鎮(zhèn)痛對產(chǎn)時發(fā)熱及圍產(chǎn)期結(jié)局的影響?；仡櫺苑治?019年6月1日至6月30日于杭州市婦產(chǎn)科醫(yī)院分娩的435例產(chǎn)婦的臨床資料。根據(jù)產(chǎn)婦是否發(fā)生產(chǎn)時發(fā)熱將其分為發(fā)熱組（=118）和非發(fā)熱組（=317）。收集產(chǎn)婦的臨床資料和實驗室檢查結(jié)果，采用Logistic回歸分析探討產(chǎn)婦硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的危險因素。兩組產(chǎn)婦分娩前后的白細(xì)胞（white blood cell，WBC）和C反應(yīng)蛋白（C-reactive protein，CRP）、胎膜早破（premature rupture of membranes，PROM）≥18h比例及新生兒出生體質(zhì)量比較，差異均有統(tǒng)計學(xué)意義（<0.05）。Logistic回歸分析結(jié)果顯示，新生兒體質(zhì)量、分娩前CRP、分娩前WBC和PROM≥18h均是產(chǎn)婦硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的獨立危險因素（<0.05）。受試者操作特征曲線結(jié)果顯示，當(dāng)硬膜外鎮(zhèn)痛時間超過427min時，產(chǎn)婦產(chǎn)時發(fā)熱的風(fēng)險顯著升高，曲線下面積為0.806，特異性和敏感度分別為72.5%和69.0%。新生兒出生體質(zhì)量、分娩前CRP、分娩前WBC、PROM≥18h均與硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱有關(guān)。持續(xù)7h以上的硬膜外鎮(zhèn)痛會增加產(chǎn)婦產(chǎn)時發(fā)熱的風(fēng)險。

硬膜外鎮(zhèn)痛；產(chǎn)時發(fā)熱；危險因素；產(chǎn)婦結(jié)局；新生兒結(jié)局

產(chǎn)婦分娩期間出現(xiàn)體溫升高的現(xiàn)象稱產(chǎn)時發(fā)熱。產(chǎn)時發(fā)熱通常體溫38.0℃及以上，可由感染性和非感染性因素所致，是新生兒腦病、新生兒窒息、新生兒敗血癥等圍產(chǎn)期不良結(jié)局的危險因素之一，發(fā)病率3.3%～7.0%[1-5]。產(chǎn)時發(fā)熱的感染性因素包括絨毛膜羊膜炎和孕婦菌血癥[6]；非感染性因素包括硬膜外鎮(zhèn)痛、前列腺素誘導(dǎo)分娩、脫水及環(huán)境溫度升高等[7]。硬膜外鎮(zhèn)痛是最常用的分娩鎮(zhèn)痛方式。研究發(fā)現(xiàn)，20%～30%接受硬膜外鎮(zhèn)痛的產(chǎn)婦會經(jīng)歷產(chǎn)時發(fā)熱[8-10]。硬膜外鎮(zhèn)痛相關(guān)的產(chǎn)時發(fā)熱可能是局部麻醉藥通過免疫調(diào)節(jié)和細(xì)胞損傷引發(fā)的非感染性炎癥[11]；也有研究提出與硬膜外鎮(zhèn)痛相關(guān)的產(chǎn)婦產(chǎn)時發(fā)熱可能導(dǎo)致不良妊娠結(jié)局，并增加新生兒并發(fā)癥的發(fā)生率[12-13]。本研究探討硬膜外鎮(zhèn)痛與產(chǎn)時發(fā)熱之間的關(guān)系及對母嬰結(jié)局的影響，現(xiàn)將結(jié)果報道如下。

1 資料與方法

1.1 研究對象

回顧性分析2019年6月1日至6月30日于杭州市婦產(chǎn)科醫(yī)院分娩的435例產(chǎn)婦的臨床資料。納入標(biāo)準(zhǔn)：①妊娠37～41周；②單活胎妊娠；③有陰道分娩條件并進(jìn)入產(chǎn)程試產(chǎn)；④在分娩過程中接受硬膜外鎮(zhèn)痛。排除標(biāo)準(zhǔn)：①臨床資料不完整；②計劃剖宮產(chǎn)；③非單胎妊娠；④死產(chǎn)；⑤胎齡37周之前分娩和先天性胎兒異常的產(chǎn)婦。根據(jù)產(chǎn)婦是否發(fā)生產(chǎn)時發(fā)熱將其分為發(fā)熱組（=118）和非發(fā)熱組（=317）。本研究經(jīng)杭州市婦產(chǎn)科醫(yī)院醫(yī)學(xué)倫理委員會批準(zhǔn)（倫理審批號：2023K3-02）。

1.2 硬膜外鎮(zhèn)痛方法

當(dāng)產(chǎn)婦子宮規(guī)律收縮且宮頸擴(kuò)張≥2cm時，給予硬膜外鎮(zhèn)痛。產(chǎn)婦左側(cè)臥位，在L2～L3椎間隙進(jìn)行硬膜外穿刺，并將硬膜外導(dǎo)管插入硬膜外腔4～5cm。鎮(zhèn)痛負(fù)荷劑量為0.1%羅哌卡因10ml。鎮(zhèn)痛設(shè)定為2ml/h連續(xù)輸注，一次應(yīng)用8ml，暫停15min后繼續(xù)泵注，最大輸注量為35ml。分娩后2h拔除硬膜外導(dǎo)管。

1.3 觀察指標(biāo)

通過查閱電子醫(yī)療記錄，獲得產(chǎn)婦實驗室檢查結(jié)果和產(chǎn)程數(shù)據(jù)及新生兒結(jié)局。產(chǎn)婦的具體指標(biāo)包括體質(zhì)量指數(shù)（body mass index，BMI）、胎膜早破（premature rupture of membranes，PROM）≥18h、分娩前白細(xì)胞（white blood cell，WBC）、分娩前C反應(yīng)蛋白（C-reactive protein，CRP）、Ⅲ度羊水胎糞污染（meconium-stained amniotic fluid Ⅲ，MSAF Ⅲ）等。新生兒結(jié)局包括1分鐘Apgar評分和新生兒重癥監(jiān)護(hù)病房住院率等。

1.4 統(tǒng)計學(xué)方法

2 結(jié)果

2.1 兩組產(chǎn)婦的一般資料比較

兩組產(chǎn)婦分娩前后的WBC和CRP、PROM≥18h比例及新生兒出生體質(zhì)量比較，差異均有統(tǒng)計學(xué)意義（<0.05），見表1。

2.2 產(chǎn)婦硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的危險因素分析

將新生兒體質(zhì)量、產(chǎn)婦的分娩前CRP、分娩前WBC、PROM≥18h、分娩后WBC和分娩后CRP納入進(jìn)行Logistic回歸分析，結(jié)果顯示新生兒體質(zhì)量、分娩前CRP、分娩前WBC和PROM≥18h均是產(chǎn)婦硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的獨立危險因素（<0.05），見表2。

表1 兩組產(chǎn)婦的一般資料比較

注：PT為凝血酶原時間；APTT為活化部分凝血活酶時間

表2 產(chǎn)婦硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的危險因素分析

2.3 硬膜外鎮(zhèn)痛持續(xù)時間與產(chǎn)時發(fā)熱的關(guān)系

通過受試者操作特征曲線（receiver operating characteristic curve，ROC曲線）分析確定硬膜外鎮(zhèn)痛持續(xù)時間的理想臨界值。結(jié)果表明，硬膜外鎮(zhèn)痛時間能很好地預(yù)測產(chǎn)時發(fā)熱，曲線下面積為0.806，閾值為427min，特異性和敏感度分別為72.5%和69.0%，見圖1。

圖1 硬膜外鎮(zhèn)痛持續(xù)時間與產(chǎn)時發(fā)熱的ROC曲線

3 討論

1989年，F(xiàn)usi首次提出產(chǎn)婦硬膜外鎮(zhèn)痛與產(chǎn)時發(fā)熱密切相關(guān)，之后硬膜外鎮(zhèn)痛引起產(chǎn)科醫(yī)生和麻醉師的廣泛興趣[14]。產(chǎn)婦產(chǎn)時發(fā)熱與硬膜外鎮(zhèn)痛的發(fā)病機(jī)制一直存在爭議[10]。既往研究表明，非感染性炎癥可能發(fā)揮潛在作用[15-16]。Riley等[17]比較分娩過程中接受硬膜外鎮(zhèn)痛與未接受硬膜外鎮(zhèn)痛的產(chǎn)婦的胎盤感染率，發(fā)現(xiàn)雖然兩組產(chǎn)婦的胎盤感染率相似，但接受硬膜外鎮(zhèn)痛的產(chǎn)婦更有可能經(jīng)歷產(chǎn)時發(fā)熱。Sultan等[9]指出，硬膜外鎮(zhèn)痛引起的發(fā)熱可能是炎癥反應(yīng)驅(qū)動的結(jié)果，潛在的炎癥因素包括硬膜外置管、分娩和局部麻醉藥的創(chuàng)傷。一項雙盲、安慰劑對照研究結(jié)果顯示，在硬膜外麻醉前給予產(chǎn)婦抗生素，并未降低產(chǎn)婦產(chǎn)時發(fā)熱及胎盤炎癥的發(fā)生率，該研究結(jié)果證實與硬膜外鎮(zhèn)痛相關(guān)的產(chǎn)婦發(fā)熱是一種非感染性炎癥[18]。硬膜外鎮(zhèn)痛通過阻斷交感神經(jīng)和引起高于鎮(zhèn)痛水平的血管收縮以減少熱損失，同時減輕疼痛、骨骼肌活動和呼吸頻率，并提高出汗閾值，進(jìn)而使體溫調(diào)節(jié)中樞發(fā)生進(jìn)一步的生物學(xué)變化，導(dǎo)致體溫升高[19]。本研究顯示硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱產(chǎn)婦的分娩前后WBC和CRP及PROM≥18h比例均明顯高于無產(chǎn)時發(fā)熱產(chǎn)婦，提示硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的情況下，要警惕感染因素存在。

Dior等[4]發(fā)現(xiàn)硬膜外鎮(zhèn)痛與產(chǎn)婦產(chǎn)時發(fā)熱有關(guān)，而產(chǎn)婦產(chǎn)時發(fā)熱是產(chǎn)科常見不良結(jié)局的重要危險因素，如產(chǎn)后出血、難產(chǎn)等。Sharpe等[10]認(rèn)為發(fā)熱對新生兒的影響包括神經(jīng)抑制癥狀，如Apgar評分降低和心肺復(fù)蘇增加；T?rnell等[20]發(fā)現(xiàn)硬膜外鎮(zhèn)痛與新生兒神經(jīng)系統(tǒng)預(yù)后不良無關(guān)，僅與新生兒Apgar評分下降有關(guān)；Zheng等[21]研究發(fā)現(xiàn)與在第二產(chǎn)程終止鎮(zhèn)痛相比，在第二產(chǎn)程持續(xù)硬膜外鎮(zhèn)痛不影響母胎結(jié)局。本研究結(jié)果顯示硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱與新生兒出生體質(zhì)量、分娩前WBC、分娩前CRP和PROM≥18h均有關(guān)。提示產(chǎn)婦若存在分娩前WBC和CRP明顯高于正常及PROM≥18h，給予硬膜外鎮(zhèn)痛時要監(jiān)測體溫，警惕產(chǎn)時發(fā)熱的發(fā)生。進(jìn)一步的ROC曲線分析顯示，硬膜外鎮(zhèn)痛持續(xù)時間超過427min（約7h）可顯著增加產(chǎn)婦產(chǎn)時發(fā)熱的風(fēng)險。提示醫(yī)護(hù)人員在整個分娩過程中監(jiān)測產(chǎn)婦體溫是非常重要和必要的，特別是硬膜外鎮(zhèn)痛時間超過7h，應(yīng)及早采取預(yù)防產(chǎn)婦產(chǎn)時發(fā)熱的措施，如降低室溫、減少衣物、補水、使用催產(chǎn)素加速分娩等。

綜上所述，新生兒出生體質(zhì)量、產(chǎn)婦的分娩前WBC、分娩前CRP和PROM≥18h均是硬膜外鎮(zhèn)痛合并產(chǎn)時發(fā)熱的獨立危險因素。超過7h的硬膜外鎮(zhèn)痛可增加產(chǎn)婦產(chǎn)時發(fā)熱的風(fēng)險。

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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

浙江省衛(wèi)生健康科技計劃項目（2022KY869）

溫海燕，電子信箱：wenhy1991@163.com

（2023–02–17）

（2023–07–14）