硬膜外鎮痛對產時發熱及圍產期結局的影響

安紅敏，鄭偉，謝中，溫海燕

硬膜外鎮痛對產時發熱及圍產期結局的影響

安紅敏1，鄭偉2，謝中1，溫海燕1

1.杭州市婦產科醫院產科，浙江杭州 310008；2.浙江大學醫學院附屬兒童醫院消化科，浙江杭州 310052

探討硬膜外鎮痛對產時發熱及圍產期結局的影響。回顧性分析2019年6月1日至6月30日于杭州市婦產科醫院分娩的435例產婦的臨床資料。根據產婦是否發生產時發熱將其分為發熱組（=118）和非發熱組（=317）。收集產婦的臨床資料和實驗室檢查結果，采用Logistic回歸分析探討產婦硬膜外鎮痛合并產時發熱的危險因素。兩組產婦分娩前后的白細胞（white blood cell，WBC）和C反應蛋白（C-reactive protein，CRP）、胎膜早破（premature rupture of membranes，PROM）≥18h比例及新生兒出生體質量比較，差異均有統計學意義（<0.05）。Logistic回歸分析結果顯示，新生兒體質量、分娩前CRP、分娩前WBC和PROM≥18h均是產婦硬膜外鎮痛合并產時發熱的獨立危險因素（<0.05）。受試者操作特征曲線結果顯示，當硬膜外鎮痛時間超過427min時，產婦產時發熱的風險顯著升高，曲線下面積為0.806，特異性和敏感度分別為72.5%和69.0%。新生兒出生體質量、分娩前CRP、分娩前WBC、PROM≥18h均與硬膜外鎮痛合并產時發熱有關。持續7h以上的硬膜外鎮痛會增加產婦產時發熱的風險。

硬膜外鎮痛；產時發熱；危險因素；產婦結局；新生兒結局

產婦分娩期間出現體溫升高的現象稱產時發熱。產時發熱通常體溫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期不良結局的危險因素之一，發病率3.3%～7.0%[1-5]。產時發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痛、前列腺素誘導分娩、脫水及環境溫度升高等[7]。硬膜外鎮痛是最常用的分娩鎮痛方式。研究發現，20%～30%接受硬膜外鎮痛的產婦會經歷產時發熱[8-10]。硬膜外鎮痛相關的產時發熱可能是局部麻醉藥通過免疫調節和細胞損傷引發的非感染性炎癥[11]；也有研究提出與硬膜外鎮痛相關的產婦產時發熱可能導致不良妊娠結局，并增加新生兒并發癥的發生率[12-13]。本研究探討硬膜外鎮痛與產時發熱之間的關系及對母嬰結局的影響，現將結果報道如下。

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日于杭州市婦產科醫院分娩的435例產婦的臨床資料。納入標準：①妊娠37～41周；②單活胎妊娠；③有陰道分娩條件并進入產程試產；④在分娩過程中接受硬膜外鎮痛。排除標準：①臨床資料不完整；②計劃剖宮產；③非單胎妊娠；④死產；⑤胎齡37周之前分娩和先天性胎兒異常的產婦。根據產婦是否發生產時發熱將其分為發熱組（=118）和非發熱組（=317）。本研究經杭州市婦產科醫院醫學倫理委員會批準（倫理審批號：2023K3-02）。

1.2 硬膜外鎮痛方法

當產婦子宮規律收縮且宮頸擴張≥2cm時，給予硬膜外鎮痛。產婦左側臥位，在L2～L3椎間隙進行硬膜外穿刺，并將硬膜外導管插入硬膜外腔4～5cm。鎮痛負荷劑量為0.1%羅哌卡因10ml。鎮痛設定為2ml/h連續輸注，一次應用8ml，暫停15min后繼續泵注，最大輸注量為35ml。分娩后2h拔除硬膜外導管。

1.3 觀察指標

通過查閱電子醫療記錄，獲得產婦實驗室檢查結果和產程數據及新生兒結局。產婦的具體指標包括體質量指數（body mass index，BMI）、胎膜早破（premature rupture of membranes，PROM）≥18h、分娩前白細胞（white blood cell，WBC）、分娩前C反應蛋白（C-reactive protein，CRP）、Ⅲ度羊水胎糞污染（meconium-stained amniotic fluid Ⅲ，MSAF Ⅲ）等。新生兒結局包括1分鐘Apgar評分和新生兒重癥監護病房住院率等。

1.4 統計學方法

2 結果

2.1 兩組產婦的一般資料比較

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

2.2 產婦硬膜外鎮痛合并產時發熱的危險因素分析

將新生兒體質量、產婦的分娩前CRP、分娩前WBC、PROM≥18h、分娩后WBC和分娩后CRP納入進行Logistic回歸分析，結果顯示新生兒體質量、分娩前CRP、分娩前WBC和PROM≥18h均是產婦硬膜外鎮痛合并產時發熱的獨立危險因素（<0.05），見表2。

表1 兩組產婦的一般資料比較

注：PT為凝血酶原時間；APTT為活化部分凝血活酶時間

表2 產婦硬膜外鎮痛合并產時發熱的危險因素分析

2.3 硬膜外鎮痛持續時間與產時發熱的關系

通過受試者操作特征曲線（receiver operating characteristic curve，ROC曲線）分析確定硬膜外鎮痛持續時間的理想臨界值。結果表明，硬膜外鎮痛時間能很好地預測產時發熱，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 硬膜外鎮痛持續時間與產時發熱的ROC曲線

3 討論

1989年，Fusi首次提出產婦硬膜外鎮痛與產時發熱密切相關，之后硬膜外鎮痛引起產科醫生和麻醉師的廣泛興趣[14]。產婦產時發熱與硬膜外鎮痛的發病機制一直存在爭議[10]。既往研究表明，非感染性炎癥可能發揮潛在作用[15-16]。Riley等[17]比較分娩過程中接受硬膜外鎮痛與未接受硬膜外鎮痛的產婦的胎盤感染率，發現雖然兩組產婦的胎盤感染率相似，但接受硬膜外鎮痛的產婦更有可能經歷產時發熱。Sultan等[9]指出，硬膜外鎮痛引起的發熱可能是炎癥反應驅動的結果，潛在的炎癥因素包括硬膜外置管、分娩和局部麻醉藥的創傷。一項雙盲、安慰劑對照研究結果顯示，在硬膜外麻醉前給予產婦抗生素，并未降低產婦產時發熱及胎盤炎癥的發生率，該研究結果證實與硬膜外鎮痛相關的產婦發熱是一種非感染性炎癥[18]。硬膜外鎮痛通過阻斷交感神經和引起高于鎮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，進而使體溫調節中樞發生進一步的生物學變化，導致體溫升高[19]。本研究顯示硬膜外鎮痛合并產時發熱產婦的分娩前后WBC和CRP及PROM≥18h比例均明顯高于無產時發熱產婦，提示硬膜外鎮痛合并產時發熱的情況下，要警惕感染因素存在。

Dior等[4]發現硬膜外鎮痛與產婦產時發熱有關，而產婦產時發熱是產科常見不良結局的重要危險因素，如產后出血、難產等。Sharpe等[10]認為發熱對新生兒的影響包括神經抑制癥狀，如Apgar評分降低和心肺復蘇增加；T?rnell等[20]發現硬膜外鎮痛與新生兒神經系統預后不良無關，僅與新生兒Apgar評分下降有關；Zheng等[21]研究發現與在第二產程終止鎮痛相比，在第二產程持續硬膜外鎮痛不影響母胎結局。本研究結果顯示硬膜外鎮痛合并產時發熱與新生兒出生體質量、分娩前WBC、分娩前CRP和PROM≥18h均有關。提示產婦若存在分娩前WBC和CRP明顯高于正常及PROM≥18h，給予硬膜外鎮痛時要監測體溫，警惕產時發熱的發生。進一步的ROC曲線分析顯示，硬膜外鎮痛持續時間超過427min（約7h）可顯著增加產婦產時發熱的風險。提示醫護人員在整個分娩過程中監測產婦體溫是非常重要和必要的，特別是硬膜外鎮痛時間超過7h，應及早采取預防產婦產時發熱的措施，如降低室溫、減少衣物、補水、使用催產素加速分娩等。

綜上所述，新生兒出生體質量、產婦的分娩前WBC、分娩前CRP和PROM≥18h均是硬膜外鎮痛合并產時發熱的獨立危險因素。超過7h的硬膜外鎮痛可增加產婦產時發熱的風險。

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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）