持续硬膜外镇痛与自控硬膜外镇痛对产妇应激反应、泌乳功能及新生儿阿氏评分的影响对比

韩丽

·临床论著·

持续硬膜外镇痛与自控硬膜外镇痛对产妇应激反应、泌乳功能及新生儿阿氏评分的影响对比

韩丽*

（济源市人民医院麻醉科，河南 济源 454651）

对比持续硬膜外镇痛与自控硬膜外镇痛对产妇应激反应、泌乳功能及新生儿阿氏评分的影响。选择2017年2月至2019年5月我院收治的98例产妇进行研究，随机分为对照组和观察组（n=49）。对照组患者以罗哌卡因与舒芬太尼持续硬膜外镇痛进行无痛分娩，观察组以相同药物行自控硬膜外镇痛。采用放射免疫法测定两组产妇分娩前、后血清促肾上腺皮质激素（Adrenocor ticotropic hormore，ACTH）、皮质醇（Cortisol，COR）、去甲肾上腺素（Norepinephrine，NE）及肾上腺素（Epinephrine，E）；分娩前、分娩后30 min、24 h、48 h以酶联免疫吸附法检测泌乳素的变化；同时进行新生儿阿氏评分。分娩后两组产妇ATCH、COR、NE及E均明显下降（P<0.05），且分娩后泌乳素水平均随时间的增加而增加（P<0.05），以观察组效果更为显著（P<0.05）。两组新生儿分娩后1 min、分娩后5 min阿氏评分对比差异均无统计学意义（P>0.05）。自控硬膜外镇痛无痛分娩与持续硬膜外镇痛新生儿阿氏评分均较高，具有较高的安全性。自控硬膜外镇痛无痛分娩可明显缓解产妇应激反应，改善泌乳功能。

持续硬膜外镇痛；自控硬膜外镇痛；产妇应激反应；泌乳功能；新生儿阿氏评分

分娩疼痛为生产过程中正常的生理现象，但因宫缩可引起子宫血管受压，加上胎儿对产道的压迫，初产妇紧张、焦虑情绪均可导致产妇在分娩过程出现剧烈疼痛而致剖宫产率明显升高[1]。无痛分娩也称分娩镇痛，指通过各种方法以减轻或消除分娩过程疼痛，随着国内生活水平的提高，对于无痛分娩的需求也逐渐上升，最理想的无痛分娩状态时既可充分镇痛，又不影响宫缩及产程，产妇可参与分娩过程[2]。硬膜外腔与蛛网膜下腔不相连，将局部麻醉剂注入硬膜外腔可使脊神经暂时麻痹而起到镇痛的作用，对脑脊液无明显影响。硬膜腔腔内存在大量的疏松结缔组织及小静脉丛，药液注入后流速较慢，但穿刺点给药可向上、下神经扩散而获得由颈神经至骶神经的神经阻滞且对产妇循环功能扰乱较轻，具有较高的安全性，同时还可避免对运动神经的阻滞而可使宫缩不受影响，使产妇在情绪状态下参与分娩。

硬膜外阻滞临床公认安全性与有效性均较高的分娩镇痛方法，持续硬膜外镇痛与自控硬膜外镇痛为临床常用的无痛分娩镇痛方式，两组均被证实可用于无痛分娩，但关于两者对产妇应激反应、泌乳功能及新生儿阿氏评分影响对比方面的研究较少[3]，因此本研究旨在通过对上述指标进行对比分析，以期为临床上两种麻醉方式的选择提供参考依据。

1 资料与方法

1.1 一般资料

选择2017年2月至2019年5月我院收治的98例产妇进行研究。

纳入标准：①足月单胎妊娠，胎位正常；②美国麻醉师协会（American Society of Anesthesiologists，ASA）分级Ⅰ~Ⅱ级；③产妇已获知情同意。

排除标准：①对麻醉药物过敏者；②妊娠并发症患者；③严重心、肝、肾功能异常者。

以随机数字表法将产妇分为2组，各49例。两组孕妇年龄、孕周BMI指数差异均无统计学意义（P>0.05）。

1.2 方法

在宫口开致2~3 cm时，取左侧卧位，在L3-4间隙行硬膜外腔穿刺置硬膜外导管，深度3~4 cm。经导管注入0.8%盐酸利多卡因注射液5 ml，待镇痛平面满意后给维持镇痛药物：枸橼酸芬太尼注射液0.2 mg，盐酸罗哌卡因注射液125 mg，以0.9%氯化钠注射液稀释至100 ml。对照组行持续硬膜外镇痛，采用微量注射泵以5 ml·h-1的速度持续泵入。观察组行自控硬膜外镇痛，采用PCEA泵以5 ml·h-1的速度泵入镇痛药物，自觉镇痛效果不满意，可增加药量，自控量2.5 ml·h-1，20 min·次-1，不超过10 ml·h-1，待宫口全开时停给药，分娩后持续给药至会阴侧口缝合完毕。

1.3 评价指标

1.3.1 应激反应

在分娩前后抽取产妇静脉血2 ml，以放射免疫法对血清促肾上腺皮质激素（Adrenocor ticotropic hormore，ACTH）、皮质醇（Cortisol，COR）、去甲肾上腺素（Norepinephrine，NE）及肾上腺素（Epinephrine，E）进行检测，试剂盒均购于美国Sigma公司；

1.3.2 泌乳功能评价

在分娩前及分娩后30 min、24 h、48 h抽取静脉血2 ml，以酶联免疫吸附法对泌乳素水平进行检测，试剂盒购于美国赛默飞世尔公司。

1.3.3 阿氏评分

对比两组新生儿分娩后1 min及分娩后5 min阿氏评分。

1.4 统计学方法

2 结果

2.1 两组产妇应激反应指标对比

分娩后两组ATCH、COR、NE及E均明显下降，其中观察组下降幅度更大（P<0.05），见表1。

表1 两组产妇应激反应指标对比（±SD，n=49）

注：与对照组相比，*P＜0.05；与分娩前相比，#P＜0.05。

2.2 两组产妇泌乳素对比

两组分娩后泌乳素水平均随时间增加而增加，观察组增加幅度高于对照组（P<0.05），见表2。

2.3 两组新生儿阿氏评分对比

两组新生儿分娩后1 min、分娩后5 min阿氏评分对比差异均无统计学意义（P>0.05），见表3。

表2 产妇泌乳素对比（±SD，n=49）

注：与对照组相比，*P＜0.05；与分娩前相比，#P＜0.05。

表3 两组新生儿阿氏评分对比（±SD，n=49）

3 讨论

分娩过程剧烈的疼痛可引起产妇神经内分泌紊乱而出现应激反应。严重者可致胎儿宫内缺氧，因此分娩镇痛不仅可减轻产妇痛苦，还可避免宫内缺氧，改善阿氏评分[4]。

本研究中两组阿氏评分对比无影响差异，提示本研究所使用的两种镇痛方式均可有效镇痛，避免新生儿缺氧。两组应激反应对比显示：分娩后两组产妇ATCH、COR、NE及E均明显下降，但观察组下降幅度更大。这可能由于观察组在持续硬膜外镇痛基础上增加自控镇痛，而该镇痛方式可根据产妇自觉疼痛情况而增加镇痛药物剂量，给药精确性更高而增强镇痛效果所致[5]。另外可能由于不同产妇的痛阈值不同，精神状态不同而影响痛阈值，自控硬膜外镇痛可使产妇自行控制镇痛药物给药量而获得控制感与满足感，有助于稳定其情绪，转移注意力而减少对神经系统的刺激，降低应激反应指标[6]。

泌乳素为多肽激素的一种，在妊娠后孕妇泌乳素水平随妊娠时间延长而升高，乳汁的分泌受泌乳素的调控，疼痛等应激反应的刺激可增加孕妇儿茶酚胺的释放，促进泌乳素抑制因子的释放而降低泌乳素水平。本研究中两组产妇在分娩后泌乳素水平均随时间的增加而增加，但观察组增加幅度均明显高于对照组，可能与观察组所采用的的自控硬膜外镇痛可有效缓解患者应激反应，减少对神经系统的影响而减少儿茶酚胺的分泌，使泌乳素水平升高有关。

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3 Capdevila X, Moulard S, Plasse C, et al. Effectiveness of epidural analgesia, continuous surgical site analgesia, and patient-controlled analgesic morphine for postoperative pain management and hyperalgesia, rehabilitation, and health-related quality of life after open nephrectomy: a prospective[J]. Anesth Analg, 2017, 124(1): 336-345.

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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)

韩丽，女，主治医师，主要从事临床麻醉工作，Email：vsamjn@163. com。

（2019-12-23）