本文關(guān)鍵詞：阿托西班用于雙胎妊娠晚期流產(chǎn)及早產(chǎn)的臨床研究　出處：《鄭州大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 雙胎妊娠 早產(chǎn) 阿托西班 療效 妊娠結(jié)局

【摘要】：隨著輔助生殖技術(shù)的發(fā)展,雙胎妊娠孕婦比例也隨之增加。雙胎妊娠屬于高危妊娠,晚期流產(chǎn)及早產(chǎn)是雙胎妊娠最主要的并發(fā)癥,同時(shí)也是引起新生兒發(fā)病及死亡的主要病因。早產(chǎn)兒的患病率和病死率與孕周密切相關(guān)。研究表明在22~28孕周,妊娠時(shí)間每延長1天,其新生兒存活率可提高3%,若延遲妊娠至30周,則存活率可增加至90%。對于治療晚期流產(chǎn)及先兆早產(chǎn),使用宮縮抑制劑盡量延長妊娠時(shí)間具有重要的臨床意義。據(jù)統(tǒng)計(jì),目前早產(chǎn)率始終徘徊在15%左右,因此,早產(chǎn)的治療成為研究熱點(diǎn)。早產(chǎn)的原因包括:炎癥及感染因素、能量代謝異常、胎兒或母親的信號引發(fā)分娩、子宮宮頸或胎盤結(jié)構(gòu)發(fā)生改變、遺傳因素等。其中早產(chǎn)患者比同孕齡婦女具有較高的催產(chǎn)素敏感性和催產(chǎn)素受體密度,阻斷催產(chǎn)素與受體結(jié)合,是治療早產(chǎn)的一種重要途徑之一。目前,最有效的催產(chǎn)素衍生物是阿托西班。阿托西班是對子宮有高度特異性的催產(chǎn)素拮抗劑,通過競爭性結(jié)合位于子宮肌層和蛻膜的縮宮素受體,阻止細(xì)胞內(nèi)鈣離子增加,從而在受體水平競爭性抑制由縮宮素導(dǎo)致的子宮收縮,使平滑肌松弛,達(dá)到治療早產(chǎn)的目的。研究表明阿托西班對子宮收縮的抑制作用與縮宮素受體含量呈正相關(guān)。其對單胎妊娠的保胎效果及安全性逐漸被國內(nèi)外所證實(shí),而缺乏應(yīng)用于雙胎妊娠方面的數(shù)據(jù)。本研究將對阿托西班用于雙胎妊娠晚期流產(chǎn)及早產(chǎn)的效果及安全性進(jìn)行探討。資料和方法1研究對象與分組1.選擇2011年6月至2015年6月孕周在24~33周我院住院的有晚期流產(chǎn)及早產(chǎn)征象的雙胎妊娠孕婦作為研究對象,納入標(biāo)準(zhǔn)為:(1)宮縮持續(xù)時(shí)間≥30s、頻率≥4次/30 min的規(guī)律宮縮;(2)宮頸管消退≥50%。排除標(biāo)準(zhǔn):胎膜早破、宮口開大≥3cm、陰道出血、子癇前期、妊娠期高血壓、嚴(yán)重的孕婦疾病、胎兒生長受限、胎兒患有染色體疾病、羊水過少、絨毛膜羊膜炎。共60例,隨機(jī)分為2組,其中小療程組30例,大療程組30例。所有入選孕婦均無繼續(xù)妊娠及使用宮縮抑制劑的禁忌證。2.經(jīng)陰道超聲測量宮頸長度方法:(1)排空膀胱后經(jīng)陰道超聲檢查;(2)探頭置于陰道前穹隆,避免過度用力;(3)標(biāo)準(zhǔn)矢狀面,將圖像放大到全屏的75%以上,測量宮頸內(nèi)口至外口的直線距離,連續(xù)測量3次后取其最短值。3.阿托西班用藥方案(輝凌(瑞典)制藥有限公司生產(chǎn)):19小時(shí)方案(小療程):首劑規(guī)格為6.75 mg,以大于1 min的速度靜脈注射;然后阿托西班注射液20ml(規(guī)格:7.5mg/ml)加入0.9%氯化鈉注射液或5%葡萄糖注射液180ml中,以300μg/ml的速度靜脈滴注3h;然后以100μg/min直至達(dá)到預(yù)期的抑制宮縮效果,總時(shí)長約18h。44小時(shí)方案(大療程):首劑規(guī)格為6.75 mg以大于1 min的速度靜脈注射;然后阿托西班注射液40ml加入0.9%氯化鈉注射液或5%葡萄糖注射液360ml中,以300μg/ml的速度靜脈滴注3h;然后以100μg/min直至達(dá)到預(yù)期的抑制宮縮效果,總時(shí)長約44h。孕婦宮縮成功抑制后重新出現(xiàn)早產(chǎn)癥狀可給予重復(fù)的治療。各孕婦入院即給予一個(gè)療程的糖皮質(zhì)激素治療。4.觀察指標(biāo):⑴大療程組與小療程組對延長孕齡48h、7d的效果及安全性的比較⑵大療程用藥方案宮頸管長度(CL)≥20mm組與CL20mm組抑制宮縮的療效比較;小療程用藥方CL≥20mm組與CL20mm組抑制宮縮的療效比較⑶產(chǎn)時(shí)、產(chǎn)后情況,新生兒發(fā)病率及死亡率。5.療效及安全性判斷標(biāo)準(zhǔn)有效:用藥后宮縮逐漸停止,宮頸口停止擴(kuò)張,繼續(xù)妊娠超過48h。無效:用藥后宮縮無減弱,48h內(nèi)分娩。安全性:任何可能的不良反應(yīng)均考慮在內(nèi),如:惡心、嘔吐、顫抖、心動(dòng)過速、低血壓、頭痛、肺水腫、出血、深靜脈血栓。2統(tǒng)計(jì)學(xué)方法采用SPSS 17.0軟件分析數(shù)據(jù)。計(jì)數(shù)資料采用百分?jǐn)?shù)、χ2檢驗(yàn)或Fisher精確檢驗(yàn),計(jì)量資料采用x±s表示,組間比較用t檢驗(yàn),以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果1阿托西班的治療效果60例應(yīng)用阿托西班雙胎妊娠患者48h未分娩者占85.0%(51/60);7d未分娩者占63.3%(38/60)。妊娠時(shí)間最短延長15h,最長延長74d。大小療程治療效果比較見表2,χ2檢驗(yàn)結(jié)果表明,大療程組的48h和7d的抑制宮縮的有效率顯著優(yōu)于小療程組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2大小療程組治療的安全性大療程組有1例出現(xiàn)頭痛、惡心,1例出現(xiàn)心慌、胸悶,均未影響治療。小療程組有1例出現(xiàn)惡心,1例皮膚瘙癢,均未影響治療。2組的不良反應(yīng)發(fā)生率比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。3不同宮頸長度用藥效果小療程用藥方案時(shí)CL≥20mm組的48h和7d抑制宮縮有效率顯著優(yōu)于CL20mm組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);大療程用藥方案時(shí)CL≥20mm組與CL20mm組相比的48h和7d有效率差異無統(tǒng)計(jì)學(xué)意義(P0.05)。4妊娠結(jié)局產(chǎn)時(shí)子宮收縮乏力占11.7%(7/60)。無產(chǎn)后出血。孕周28周分娩17例,28~34周分娩29例,≥34周分娩14例。新生兒存活101例,死亡19例。結(jié)論1.阿托西班大療程和小療程均可有效延長雙胎妊娠晚期流產(chǎn)及早產(chǎn)的妊娠時(shí)間。大療程方案更有效。并不增加母兒的不良反應(yīng)。2.雙胎妊娠晚期流產(chǎn)及先兆早產(chǎn)孕婦CL20mm時(shí)大療程用藥效果更好。3.阿托西班大療程用藥并不增加母兒的不良反應(yīng),且不增加新生兒并發(fā)癥的風(fēng)險(xiǎn)。
[Abstract]:With the development of assisted reproductive technology, also increased the proportion of pregnant women with twin pregnancy. Twin pregnancy belongs to high-risk pregnancy, late abortion and premature birth is the main complication of twin pregnancy, but also cause of neonatal morbidity and the major causes of death in premature infants. The incidence and death rate of disease is closely related with gestational age. The study showed that in the the 22~28 weeks of gestation, pregnancy time extended by 1 days, the survival rate can be increased by 3% to 30 weeks of pregnancy, if delayed, the survival rate can be increased to 90%. for the treatment of late abortion and preterm labor, has important clinical significance for the use of tocolytic to prolong pregnancy. According to statistics, the preterm birth rate has remained at 15% so, therefore, the treatment of preterm labor has become a research hotspot. Including the reasons of premature: inflammation and infection, abnormal energy metabolism, signal caused by fetal or maternal childbirth, uterine cervical or placental structure Change, genetic factors. The preterm patients than the same gestational age women have high sensitivity to oxytocin and oxytocin receptor density, blocking oxytocin combined with the receptor, is an important way of treatment of preterm birth. At present, the most effective oxytocin derivatives is A Tosi Ben. A Tosi Ben is on the highly specific oxytocin antagonists by competitive binding in myometrial and decidual oxytocin receptor, prevented the increase in intracellular calcium, which at the receptor level of competitive inhibition by oxytocin induced uterine contraction, smooth muscle relaxation, to the treatment of premature. Study shows that A Tosi Ben's inhibitory effect on uterine contraction with oxytocin receptor concentrations were positively correlated. The clinical effects and safety of single pregnancy has been confirmed at home and abroad, and the lack of application in twin pregnancy data on this study. A Tosi Ben used of late abortion and premature birth of the efficacy and safety of twin pregnancy. Materials and methods: 1 subjects and groups from June 2011 to June 2015 1. gestational weeks 24~33 weeks in our hospital have twin late abortion and premature birth signs of pregnant women as the research object, the inclusion criteria: (1) sustained contractions time is more than 30s, the frequency is more than 4 times /30 min of uterine contractions; (2) the cervical canal subsided more than 50%. exclusion criteria: premature rupture of membranes, cervix than 3cm, vaginal bleeding, pre eclampsia, gestational hypertension, severe illness in pregnant women, fetal growth restriction, fetus with chromosomal diseases, oligohydramnios, villi chorioamnionitis. A total of 60 patients were randomly divided into 2 groups, the treatment group of 30 cases of small and large treatment group of 30 cases. All pregnant women were not to continue the pregnancy and use of tocolytic contraindication to.2. by transvaginal ultrasound measurement of cervical length method: (1) emptying Bladder after transvaginal ultrasound; (2) probe in the anterior vaginal fornix, to avoid excessive force; (3) the standard sagittal image to enlarge more than 75% full screen, linear distance measurement in the cervix mouth to mouth, continuous measurement after 3 times the shortest.3. regimen (Hui A Tosi Ben Ling (Sweden) pharmaceutical Co.): 19 hour plan (small course): the first agent specifications for 6.75 mg, the speed of intravenous injection of more than 1 min; then A Tosi Ben injection 20ml (size: 7.5mg/ml) with 0.9% or 5% Sodium Chloride Injection Glucose Injection 180ml, with a rate of 3H intravenous infusion of 300 g/ml; and based on 100 g/min until the desired tocolytic effect, the total time of about 18h.44 hours (of course) scheme: speed of intravenous injection of the first dose of specifications for 6.75 mg with more than 1 min; and A Tosi Ben 40ml joined Sodium Chloride Injection 0.9% injection or 5% glucose injection Liquid 360ml, with a rate of 3H intravenous infusion of 300 g/ml; and then to 100 g/min until the desired tocolytic effect, the total length of about 44h. to inhibit the contraction of pregnant women to symptoms of preterm labor can give repeated treatment. Glucocorticoid treatment.4. observation indexes of all pregnant women admitted to a course the large and small group: treatment group treatment of prolonged gestational age 48h, compared to the treatment regimen of cervical high efficacy and safety of 7D tube length (CL) than the curative effect comparison of 20mm group and CL20mm group tocolytic treatment with prescription; small CL = 20mm group and CL20mm group to compare the efficacy of the product inhibition of contraction when postpartum and neonatal morbidity and mortality of.5. efficacy and safety criteria: effective medication uterine cervix gradually stop, stop the expansion, to continue the pregnancy more than 48h. medication invalid: uterine contraction without weakening, 48h delivery security: any. Adverse reaction are considered, such as nausea, vomiting, shivering, tachycardia, hypotension, headache, pulmonary edema, hemorrhage, deep venous thrombosis.2 statistical methods using SPSS 17 software to analyze data. Count data using chi square test or 2 percentage, Fisher exact test, measurement data using the X + s group. Compared with t test, with P0.05 as the difference was statistically significant. The treatment effect of 60 cases of the application results of the 1 A Tosi Ben A Tosi Ben twin pregnancy 48h delivery accounted for 85% (51/60); 7d delivery accounted for 63.3% (38/60) of pregnancy. The shortest time extension of 15h, the longest extended treatment effect size of 74d. treatment see Table 2, 2 test results showed that the inhibition of contraction large treatment group of 48h and 7d was significantly better than the small group, the difference was statistically significant (P0.05).2 treatment group safety treatment group with 1 cases of headache, nausea, 1 cases Palpitation, chest tightness, did not affect the treatment. Small treatment group had 1 cases of nausea, 1 cases of skin itching, did not affect the occurrence of adverse reactions in the treatment group.2 rate had no significant difference (P0.05) of.3 in different cervical length medication effect of drug treatment for small CL = 20mm group 48h and 7d with inhibition of contraction the efficiency was higher than that of CL20mm group, the difference was statistically significant (P0.05); large drug treatment scheme CL = 20mm group compared with CL20mm group 48h and 7d there was no significant difference in efficiency (P0.05).4 pregnancy outcome uterine atony accounted for 11.7% (7/60). No postpartum hemorrhage. 28 weeks gestation delivery 17 example, 28~34 weeks delivery 29 cases over 34 weeks in 14 cases of delivery. Neonatal survival in 101 cases, 19 cases died. Conclusion the 1. big and small atosiban can effectively prolong the course of treatment of late abortion and premature birth of twin pregnancy pregnancy time. Large treatment regimen was more effective. The mother does not increase Good response to.2., twin pregnancy, late pregnancy, and threatened premature delivery of pregnant women had better effect when they were treated with CL20mm for a large period of time..3. A Tosi Ben did not increase the adverse reaction of mother and child, and did not increase the risk of neonatal complications.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R714.21

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