韓麗

·臨床論著·

持續(xù)硬膜外鎮(zhèn)痛與自控硬膜外鎮(zhèn)痛對(duì)產(chǎn)婦應(yīng)激反應(yīng)、泌乳功能及新生兒阿氏評(píng)分的影響對(duì)比

韓麗*

（濟(jì)源市人民醫(yī)院麻醉科，河南 濟(jì)源 454651）

對(duì)比持續(xù)硬膜外鎮(zhèn)痛與自控硬膜外鎮(zhèn)痛對(duì)產(chǎn)婦應(yīng)激反應(yīng)、泌乳功能及新生兒阿氏評(píng)分的影響。選擇2017年2月至2019年5月我院收治的98例產(chǎn)婦進(jìn)行研究，隨機(jī)分為對(duì)照組和觀察組（n=49）。對(duì)照組患者以羅哌卡因與舒芬太尼持續(xù)硬膜外鎮(zhèn)痛進(jìn)行無(wú)痛分娩，觀察組以相同藥物行自控硬膜外鎮(zhèn)痛。采用放射免疫法測(cè)定兩組產(chǎn)婦分娩前、后血清促腎上腺皮質(zhì)激素（Adrenocor ticotropic hormore，ACTH）、皮質(zhì)醇（Cortisol，COR）、去甲腎上腺素（Norepinephrine，NE）及腎上腺素（Epinephrine，E）；分娩前、分娩后30 min、24 h、48 h以酶聯(lián)免疫吸附法檢測(cè)泌乳素的變化；同時(shí)進(jìn)行新生兒阿氏評(píng)分。分娩后兩組產(chǎn)婦ATCH、COR、NE及E均明顯下降（P<0.05），且分娩后泌乳素水平均隨時(shí)間的增加而增加（P<0.05），以觀察組效果更為顯著（P<0.05）。兩組新生兒分娩后1 min、分娩后5 min阿氏評(píng)分對(duì)比差異均無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。自控硬膜外鎮(zhèn)痛無(wú)痛分娩與持續(xù)硬膜外鎮(zhèn)痛新生兒阿氏評(píng)分均較高，具有較高的安全性。自控硬膜外鎮(zhèn)痛無(wú)痛分娩可明顯緩解產(chǎn)婦應(yīng)激反應(yīng)，改善泌乳功能。

持續(xù)硬膜外鎮(zhèn)痛；自控硬膜外鎮(zhèn)痛；產(chǎn)婦應(yīng)激反應(yīng)；泌乳功能；新生兒阿氏評(píng)分

分娩疼痛為生產(chǎn)過(guò)程中正常的生理現(xiàn)象，但因?qū)m縮可引起子宮血管受壓，加上胎兒對(duì)產(chǎn)道的壓迫，初產(chǎn)婦緊張、焦慮情緒均可導(dǎo)致產(chǎn)婦在分娩過(guò)程出現(xiàn)劇烈疼痛而致剖宮產(chǎn)率明顯升高[1]。無(wú)痛分娩也稱分娩鎮(zhèn)痛，指通過(guò)各種方法以減輕或消除分娩過(guò)程疼痛，隨著國(guó)內(nèi)生活水平的提高，對(duì)于無(wú)痛分娩的需求也逐漸上升，最理想的無(wú)痛分娩狀態(tài)時(shí)既可充分鎮(zhèn)痛，又不影響宮縮及產(chǎn)程，產(chǎn)婦可參與分娩過(guò)程[2]。硬膜外腔與蛛網(wǎng)膜下腔不相連，將局部麻醉劑注入硬膜外腔可使脊神經(jīng)暫時(shí)麻痹而起到鎮(zhèn)痛的作用，對(duì)腦脊液無(wú)明顯影響。硬膜腔腔內(nèi)存在大量的疏松結(jié)締組織及小靜脈叢，藥液注入后流速較慢，但穿刺點(diǎn)給藥可向上、下神經(jīng)擴(kuò)散而獲得由頸神經(jīng)至骶神經(jīng)的神經(jīng)阻滯且對(duì)產(chǎn)婦循環(huán)功能擾亂較輕，具有較高的安全性，同時(shí)還可避免對(duì)運(yùn)動(dòng)神經(jīng)的阻滯而可使宮縮不受影響，使產(chǎn)婦在情緒狀態(tài)下參與分娩。

硬膜外阻滯臨床公認(rèn)安全性與有效性均較高的分娩鎮(zhèn)痛方法，持續(xù)硬膜外鎮(zhèn)痛與自控硬膜外鎮(zhèn)痛為臨床常用的無(wú)痛分娩鎮(zhèn)痛方式，兩組均被證實(shí)可用于無(wú)痛分娩，但關(guān)于兩者對(duì)產(chǎn)婦應(yīng)激反應(yīng)、泌乳功能及新生兒阿氏評(píng)分影響對(duì)比方面的研究較少[3]，因此本研究旨在通過(guò)對(duì)上述指標(biāo)進(jìn)行對(duì)比分析，以期為臨床上兩種麻醉方式的選擇提供參考依據(jù)。

1 資料與方法

1.1 一般資料

選擇2017年2月至2019年5月我院收治的98例產(chǎn)婦進(jìn)行研究。

納入標(biāo)準(zhǔn)：①足月單胎妊娠，胎位正常；②美國(guó)麻醉師協(xié)會(huì)（American Society of Anesthesiologists，ASA）分級(jí)Ⅰ~Ⅱ級(jí)；③產(chǎn)婦已獲知情同意。

排除標(biāo)準(zhǔn)：①對(duì)麻醉藥物過(guò)敏者；②妊娠并發(fā)癥患者；③嚴(yán)重心、肝、腎功能異常者。

以隨機(jī)數(shù)字表法將產(chǎn)婦分為2組，各49例。兩組孕婦年齡、孕周BMI指數(shù)差異均無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。

1.2 方法

在宮口開(kāi)致2~3 cm時(shí)，取左側(cè)臥位，在L3-4間隙行硬膜外腔穿刺置硬膜外導(dǎo)管，深度3~4 cm。經(jīng)導(dǎo)管注入0.8%鹽酸利多卡因注射液5 ml，待鎮(zhèn)痛平面滿意后給維持鎮(zhèn)痛藥物：枸櫞酸芬太尼注射液0.2 mg，鹽酸羅哌卡因注射液125 mg，以0.9%氯化鈉注射液稀釋至100 ml。對(duì)照組行持續(xù)硬膜外鎮(zhèn)痛，采用微量注射泵以5 ml·h-1的速度持續(xù)泵入。觀察組行自控硬膜外鎮(zhèn)痛，采用PCEA泵以5 ml·h-1的速度泵入鎮(zhèn)痛藥物，自覺(jué)鎮(zhèn)痛效果不滿意，可增加藥量，自控量2.5 ml·h-1，20 min·次-1，不超過(guò)10 ml·h-1，待宮口全開(kāi)時(shí)停給藥，分娩后持續(xù)給藥至?xí)巶?cè)口縫合完畢。

1.3 評(píng)價(jià)指標(biāo)

1.3.1 應(yīng)激反應(yīng)

在分娩前后抽取產(chǎn)婦靜脈血2 ml，以放射免疫法對(duì)血清促腎上腺皮質(zhì)激素（Adrenocor ticotropic hormore，ACTH）、皮質(zhì)醇（Cortisol，COR）、去甲腎上腺素（Norepinephrine，NE）及腎上腺素（Epinephrine，E）進(jìn)行檢測(cè)，試劑盒均購(gòu)于美國(guó)Sigma公司；

1.3.2 泌乳功能評(píng)價(jià)

在分娩前及分娩后30 min、24 h、48 h抽取靜脈血2 ml，以酶聯(lián)免疫吸附法對(duì)泌乳素水平進(jìn)行檢測(cè)，試劑盒購(gòu)于美國(guó)賽默飛世爾公司。

1.3.3 阿氏評(píng)分

對(duì)比兩組新生兒分娩后1 min及分娩后5 min阿氏評(píng)分。

1.4 統(tǒng)計(jì)學(xué)方法

2 結(jié)果

2.1 兩組產(chǎn)婦應(yīng)激反應(yīng)指標(biāo)對(duì)比

分娩后兩組ATCH、COR、NE及E均明顯下降，其中觀察組下降幅度更大（P<0.05），見(jiàn)表1。

表1 兩組產(chǎn)婦應(yīng)激反應(yīng)指標(biāo)對(duì)比（±SD，n=49）

注：與對(duì)照組相比，*P＜0.05；與分娩前相比，#P＜0.05。

2.2 兩組產(chǎn)婦泌乳素對(duì)比

兩組分娩后泌乳素水平均隨時(shí)間增加而增加，觀察組增加幅度高于對(duì)照組（P<0.05），見(jiàn)表2。

2.3 兩組新生兒阿氏評(píng)分對(duì)比

兩組新生兒分娩后1 min、分娩后5 min阿氏評(píng)分對(duì)比差異均無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05），見(jiàn)表3。

表2 產(chǎn)婦泌乳素對(duì)比（±SD，n=49）

注：與對(duì)照組相比，*P＜0.05；與分娩前相比，#P＜0.05。

表3 兩組新生兒阿氏評(píng)分對(duì)比（±SD，n=49）

3 討論

分娩過(guò)程劇烈的疼痛可引起產(chǎn)婦神經(jīng)內(nèi)分泌紊亂而出現(xiàn)應(yīng)激反應(yīng)。嚴(yán)重者可致胎兒宮內(nèi)缺氧，因此分娩鎮(zhèn)痛不僅可減輕產(chǎn)婦痛苦，還可避免宮內(nèi)缺氧，改善阿氏評(píng)分[4]。

本研究中兩組阿氏評(píng)分對(duì)比無(wú)影響差異，提示本研究所使用的兩種鎮(zhèn)痛方式均可有效鎮(zhèn)痛，避免新生兒缺氧。兩組應(yīng)激反應(yīng)對(duì)比顯示：分娩后兩組產(chǎn)婦ATCH、COR、NE及E均明顯下降，但觀察組下降幅度更大。這可能由于觀察組在持續(xù)硬膜外鎮(zhèn)痛基礎(chǔ)上增加自控鎮(zhèn)痛，而該鎮(zhèn)痛方式可根據(jù)產(chǎn)婦自覺(jué)疼痛情況而增加鎮(zhèn)痛藥物劑量，給藥精確性更高而增強(qiáng)鎮(zhèn)痛效果所致[5]。另外可能由于不同產(chǎn)婦的痛閾值不同，精神狀態(tài)不同而影響痛閾值，自控硬膜外鎮(zhèn)痛可使產(chǎn)婦自行控制鎮(zhèn)痛藥物給藥量而獲得控制感與滿足感，有助于穩(wěn)定其情緒，轉(zhuǎn)移注意力而減少對(duì)神經(jīng)系統(tǒng)的刺激，降低應(yīng)激反應(yīng)指標(biāo)[6]。

泌乳素為多肽激素的一種，在妊娠后孕婦泌乳素水平隨妊娠時(shí)間延長(zhǎng)而升高，乳汁的分泌受泌乳素的調(diào)控，疼痛等應(yīng)激反應(yīng)的刺激可增加孕婦兒茶酚胺的釋放，促進(jìn)泌乳素抑制因子的釋放而降低泌乳素水平。本研究中兩組產(chǎn)婦在分娩后泌乳素水平均隨時(shí)間的增加而增加，但觀察組增加幅度均明顯高于對(duì)照組，可能與觀察組所采用的的自控硬膜外鎮(zhèn)痛可有效緩解患者應(yīng)激反應(yīng)，減少對(duì)神經(jīng)系統(tǒng)的影響而減少兒茶酚胺的分泌，使泌乳素水平升高有關(guān)。

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Comparative study of effects of continuous epidural analgesia and self-controlled epidural analgesia on maternal stress response, lactation function and neonatal Apgar score

Han Li*

(Department of Anesthesiology, The People's Hospital of Jiyuan, Jiyuan 454651, Henan)

To compare the effects of continuous epidural analgesia and self-controlled epidural analgesia on stress response, lactation function and neonatal Apgar score.A total of 98 maternal patients admitted to our hospital from February 2017 to May 2019 were selected and randomly divided into control group and observation group (n=49). The patients in the control group received continuous epidural analgesia with ropivacaine and sufentanil for painless delivery, and the patients in the observation group received self-control epidural analgesia with the same drug. The serum levels of adrenocorticotropic hormone (ACTH), cortisol (COR), norepinephrine (NE) and epinephrine (E) were measured by radioimmunoassay; and the changes of prolactin were detected by enzyme-linked immunosorbent assay before delivery, 30 minutes, 24 hours and 48 hours after delivery. Also the neonatal Apgar scores were evaluated.Compared with pre-delivery, ATCH, COR, NE and E of all patients were decreased significantly (P<0.05), and the level of prolactin was increased with time (P<0.05), especially in the observation group (P<0.05). There was no significant difference in the neonatal Apgar between the two groups at 1 min and 5 min after delivery (P>0.05).Both the self-control epidural analgesia and the continuous epidural analgesia had a higher Apgar score and a higher safety. Moreover, self-control epidural analgesia could significantly alleviate the stress response of the parturient and improve the lactation function.

Continuous epidural analgesia; Self-controlled epidural analgesia; Maternal stress response; Lactation function; Neonatal apgar score

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial

Lagae L, Sullivan J, Knupp K, et al.

METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we enrolled children and young adults with Dravet syndrome. After a 6-week observation period to establish baseline monthly convulsive seizure frequency (MCSF; convulsive seizures were defined as hemiclonic, tonic, clonic, tonic-atonic, generalised tonic-clonic, and focal with clearly observable motor signs), patients were randomly assigned through an interactive web response system in a 1: 1: 1 ratio to placebo, fenfluramine 0.2 mg/kg per day, or fenfluramine 0.7 mg/kg per day, added to existing antiepileptic agents for 14 weeks. The primary outcome was the change in mean monthly frequency of convulsive seizures during the treatment period compared with baseline in the 0.7 mg/kg per day group versus placebo; 0.2 mg/kg per day versus placebo was assessed as a key secondary outcome. Analysis was by modified intention to treat. Safety analyses included all participants who received at least one dose of study medication. This trial is registered with Clinical Trials. gov with two identical protocols NCT02682927 and NCT02826863.

FINDINGS: Between Jan 15, 2016, and Aug 14, 2017, we assessed 173 patients, of whom 119 patients (mean age 9.0 years, 64 [54%] male) were randomly assigned to receive either fenfluramine 0.2 mg/kg per day (39), fenfluramine 0.7 mg/kg per day (40) or placebo (40). During treatment, the median reduction in seizure frequency was 74.9% in the fenfluramine 0.7 mg/kg group (from median 20.7 seizures per 28 days to 4.7 seizures per 28 days), 42.3% in the fenfluramine 0.2 mg/kg group (from median 17.5 seizures per 28 days to 12.6 per 28 days), and 19.2% in the placebo group (from median 27.3 per 28 days to 22.0 per 28 days). The study met its primary efficacy endpoint, with fenfluramine 0.7 mg/kg per day showing a 62.3% greater reduction in mean MCSF compared with placebo (95% CI 47.7-72.8, p<0.0001); fenfluramine 0.2 mg/kg per day showed a 32.4% reduction in mean MCSF compared with placebo (95% CI 6.2-52.3, p=0.0209). The most common adverse events (occurring in at least 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension.

INTERPRETATION: In Dravet syndrome, fenfluramine provided significantly greater reduction in convulsive seizure frequency compared with placebo and was generally well tolerated, with no observed valvular heart disease or pulmonary arterial hypertension. Fenfluramine could be an important new treatment option for patients with Dravet syndrome.

(From Lancet. 2020, 394(10216): 2243-2254)

韓麗，女，主治醫(yī)師，主要從事臨床麻醉工作，Email：vsamjn@163. com。

（2019-12-23）