卡前列素氨丁審稿三醇聯(lián)合卡貝縮宮素對剖宮產(chǎn)后出血患者

1、 卡前列素氨丁三醇聯(lián)合卡貝縮宮素對剖宮產(chǎn)后出血患者NO、NOS、FIB、D-dimer及泌乳功能的影響 摘要目的：研究卡前列素氨丁三醇聯(lián)合卡貝縮宮素對剖宮產(chǎn)后出血患者一氧化氮（NO）、一氧化氮合酶（NOS）、纖維蛋白原( FIB)、D-二聚體( D-dimer)及泌乳功能的影響。方法：選取我院2015年6月至2017年6月具有剖宮產(chǎn)手術(shù)指證的孕產(chǎn)婦119例，分為觀察組和對照組，對照組給予注射卡前列素氨丁三醇治療，觀察組給予注射卡前列素氨丁三醇聯(lián)合卡貝縮宮素治療。觀察兩組治療后臨床療效，并檢測治療前后NO、NOS、FIB、D-dimer水平以及泌乳功能。結(jié)果：治療后，觀察組子宮復(fù)舊有效率為93.

2、2%明顯高于對照組子宮復(fù)舊有效率74.6%，差異顯著（P0.05）；觀察組NO、NOS、FIB、D-dimer水平均顯著低于對照組，比較具有統(tǒng)計(jì)學(xué)意義（P0.05）；觀察組術(shù)后2h出血量、術(shù)后24h出血量、產(chǎn)后出血率、宮縮持續(xù)時(shí)間及惡露持續(xù)時(shí)間均低于對照組，比較具有統(tǒng)計(jì)學(xué)意義（P0.05）；觀察組泌乳時(shí)間低于對照，觀察組產(chǎn)后1d泌乳量評分及產(chǎn)后2d泌乳量評分均高于對照組，比較具有統(tǒng)計(jì)學(xué)意義（P0.05）。結(jié)論:卡前列素氨丁三醇聯(lián)合卡貝縮宮素治療剖宮產(chǎn)產(chǎn)后出血患者，有效降低患者NO、NOS、FIB、D-dimer水平及2h出血量、術(shù)后24h出血量、產(chǎn)后出血率、宮縮持續(xù)時(shí)間及惡露持續(xù)時(shí)間，改善患者

3、泌乳時(shí)間，提高患者1d泌乳量評分及產(chǎn)后2d泌乳量評分?！娟P(guān)鍵詞】卡前列素氨丁三醇；卡貝縮宮素；NO；FIB；D-dimer；NOS；剖宮產(chǎn)產(chǎn)后出血中圖分類號：R714.62 文獻(xiàn)標(biāo)識碼：A 文章編號：Effects of caffeine tromethamine combined with carbene oxytocin on NO, NOS, FIB, D-dimer and lactation in patients with postpartum hemorrhageAbstract Objective: To study effects of caffeine tromethami

4、ne combined with carbene oxytocin on NO, NOS, FIB, D-dimer and lactation in patients with postpartum hemorrhage. Methods: 118 patients of cesarean section bleeding whoreceived therapy from June 2015 to June 2017in our hospital wereselected as research objects. According to different treatment option

5、s，those patients were divided into the control group ( n = 59) and the observation group ( n = 59)，the control group was treated withCard prostaglandin tromethamine drug therapy, while the observation group was treated with Prostaglandin tromethamine combined with carbene oxytocin, the clinical effi

6、cacy of the two groups was observed and the levels of NO, NOS, FIB, D-dimer and lactation were measured before and after treatment. Results: After treatment, the effective rate of uterine recovery was 93.2% in the observation group, which was significantly higher than that in the control group (74.6

7、%). The difference was significant (P 0.05).the levels of NO, NOS, FIB and D-dimer in the observation group were significantly lower than those in the control group (P 0.05). the time of lactation in the observation group was lower than that in the control group (P 0.05), and the time of postoperati

8、ve hemorrhage, postpartum hemorrhage rate, duration of uterine contusion and duration of lochia were lower than those of the control group (P 0.05). The scores of lactation and postpartum 2d lactation were significantly higher in the observation group than in the control group (P 0.05），具有可比性。1.2方法所有

9、產(chǎn)婦均采用子宮下段橫切口剖宮產(chǎn)術(shù)，胎兒娩出后，對照組給予卡前列素氨丁三醇注射液（生產(chǎn)廠家：Pharmacia & Upjohn company ，1ml：250g，進(jìn)口藥物注冊證號：H20120388）250 g 宮體內(nèi)注射，術(shù)后2h再注射一次。觀察組在對照組治療基礎(chǔ)上聯(lián)合使用卡貝縮宮素（輝凌制藥有限公司， 每支100g：1ml ，20150101）100g：(1ml)，靜脈注射，連續(xù)使用兩天。1.3觀察指標(biāo)記錄所有產(chǎn)婦術(shù)后2、24h出血量，產(chǎn)后出血發(fā)生率、子宮收縮持續(xù)時(shí)間、惡露持續(xù)時(shí)間。FIB采用免疫比濁法；D-dimer采用ELISA法檢測。產(chǎn)后出血量計(jì)算方法：出血量=胎兒娩出后接血敷料濕

10、重( g)接血前敷料干重( g) /1. 05( 血液比重， g/mL) 。泌乳時(shí)間為胎盤娩出后至乳房第一次溢乳時(shí)間；泌乳量評分：擠奶乳汁表現(xiàn)為噴射狀，吸允后乳房依然沒有排空為3分；手法擠奶存在奶乳汁溢出情況，哺乳時(shí)間超過8次/d，新生兒大便超1次/d，小便超5次/d，哺乳后嬰兒較安全，乳房松軟為2分；不能滿足嬰兒，需要添加一些代乳品為1分；沒有乳汁分泌為0分。療效標(biāo)準(zhǔn)參照相關(guān)文獻(xiàn)進(jìn)行10：（1）子宮復(fù)舊良好：產(chǎn)婦子宮收縮好；（2）子宮復(fù)舊不良：產(chǎn)婦子宮收縮差。1.4統(tǒng)計(jì)學(xué)分析本研究數(shù)據(jù)選擇spss18.0進(jìn)行統(tǒng)計(jì)，比較計(jì)量資料采用t檢驗(yàn)，計(jì)數(shù)資料采用2檢驗(yàn)，等級資料比較則用秩和檢驗(yàn)，當(dāng)P0.

11、05時(shí)表示差異顯著。2結(jié)果2.1兩組產(chǎn)婦子宮復(fù)舊療效比較:治療后，觀察組子宮復(fù)舊有效率為93.2%明顯高于對照組子宮復(fù)舊有效率74.6%，差異顯著（P0.05）；治療后，觀察組FIB、D-Dimer檢測值均低于對照組FIB、D-Dimer檢測值，差異具有比較意義（P0.05）；治療后，觀察組NO、NOS的水平均低于對照組NO、NOS的水平，差異具有比較意義（P0.05）。見表3。表3 兩組患者治療前后NO、NOS的水平比較（s）Table 3 Comparison of NO、NOS levels between the two groups before and after treatmen

12、t（s）GroupnTimeNO（ m mo l /L）NOS（U/mL）Observation group59Before treatment105.2411.3738.324.71After treatment41.325.27ab18.282.58abControl group59Before treatment103.3311.2137.674.77After treatment88.199.38b31.564.01bNote: Compared with the control group, aP0.05; Compared with Before treatment, bP 0.0

13、5.2.4兩組患者術(shù)后出血情況比較：觀察組術(shù)后2h出血量為（235.3235.19）、術(shù)后24h出血量為（301.3434.11）、產(chǎn)后出血率為（5.1%）、宮縮持續(xù)時(shí)間為（1.550.23）及惡露持續(xù)時(shí)間為（15.332.87）均低于對照組術(shù)后2h出血量為（367.8340.89）、術(shù)后24h出血量為（453.1949.35）、產(chǎn)后出血率為（18.6%）、宮縮持續(xù)時(shí)間為（3.270.42）及惡露持續(xù)時(shí)間為（21.193.12），差異具有統(tǒng)計(jì)學(xué)意義（P0.05）。見表4。表4 兩組患者術(shù)后出血情況比較（s）Table 4 Comparison of postoperative bleeding

14、 in both groups（s）Groupn2 hours after surgery bleeding（ml）24 hours after surgery bleeding（ml）Postpartum hemorrhage rate n（%）Contractions lasted（h）The duration of the lochia（d）Observation group59235.3235.19a301.3434.11a3（5.1）a1.550.23a15.332.87aControl group59367.8340.89453.1949.3511（18.6）3.270.4221.

15、193.12Note: Compared with the control group, aP0.052.5兩組患者產(chǎn)后泌乳時(shí)間和泌乳量評分比較：觀察組泌乳時(shí)間為（20.383.18）低于對照組泌乳時(shí)間（27.083.53）；觀察組產(chǎn)后1d泌乳量評分為（1.570.26）及產(chǎn)后2d泌乳量評分為（1.970.31）均高于對照組產(chǎn)后1d泌乳量評分為（1.210.19）及產(chǎn)后2d泌乳量評分為（1.530.25），差異具有統(tǒng)計(jì)學(xué)意義（P0.05）。見表5。表5 兩組患者產(chǎn)后泌乳時(shí)間和泌乳量評分比較（s）Table 5 Comparison of postpartum lactation time an

16、d lactation score between the two groups（s）GroupnLactation time（h）Postpartum 1d lactation score（Minute）Postpartum 2d lactation score（Minute）Observation group5920.383.18a1.570.26a1.970.31aControl group5927.083.531.210.191.530.25Note: Compared with the control group, aP0.053討論產(chǎn)后出血是婦產(chǎn)科常見的并發(fā)癥，發(fā)病原因較多，包括宮

17、縮乏力、凝血功能障礙、胎盤組織功能異常等，其中宮縮乏力是常見的發(fā)病原因11,12。引起宮縮乏力的原因主要是產(chǎn)婦精神緊張、體質(zhì)虛弱、子宮肌壁損傷及患有慢性疾病等。剖宮產(chǎn)與正常陰道分娩比較，剖宮產(chǎn)產(chǎn)婦一般存在巨大兒、多胎妊娠、前置胎盤等高危因素，加上麻醉、手術(shù)等影響，產(chǎn)后出血率顯著提高，對剖宮產(chǎn)產(chǎn)婦及新生兒造成嚴(yán)重威脅13。因此，預(yù)測剖宮產(chǎn)產(chǎn)后出血史剖宮產(chǎn)手術(shù)過程中的一個(gè)重要環(huán)節(jié)14。D-dimer是交聯(lián)纖維蛋白的一種降解產(chǎn)物，主要反映纖維蛋白溶解功能15。機(jī)體血管內(nèi)有活化的血栓形成及纖維溶解活動，D-dimer就會升高16。對產(chǎn)后出血具有一定的預(yù)測作用。通過D-dimer檢測值變化，是判斷剖宮產(chǎn)

18、產(chǎn)后出血的危險(xiǎn)因素17。FIB由肝臟合成糖蛋白，當(dāng)水平升高時(shí)，容易形成血栓18。是一種由是一種由A、B和v鏈組成的二聚體，存在于吸附血漿中19。具有促進(jìn)血小板聚集、平滑肌的生長、內(nèi)皮細(xì)胞的收縮、增加血液粘滯性等作用，容易引起內(nèi)細(xì)胞損傷。對預(yù)防和治療剖宮產(chǎn)出血患者具有重要臨床意義，通過檢測產(chǎn)婦FIB變化，診斷出患者出血發(fā)生率20。NO既是一種有細(xì)胞毒性的效應(yīng)器，又是一種生物體許多部分的信號分子，具有較為復(fù)雜的生物學(xué)效應(yīng)，促進(jìn)毛細(xì)血管的滲出21,22。NO具有抑制宮縮的作用，與子宮平滑肌活動密切相關(guān)。NOS是機(jī)體內(nèi)的一氧化合成的限速酶，其活性與NO水平相關(guān)。產(chǎn)婦的子宮肌層、胎盤組織等存在不同的NO

19、S活性，產(chǎn)婦在妊娠中期檢測到NOS的穩(wěn)定表達(dá)，與宮縮乏力性產(chǎn)后出血的發(fā)生息息相關(guān)23。通過檢測NO與NOS水平變化，觀察產(chǎn)婦胎盤血流量、子宮平滑肌松弛度變化。泌乳是多種激素作用于已發(fā)育的乳腺引起的。產(chǎn)婦通過調(diào)節(jié)內(nèi)分泌系統(tǒng)，促進(jìn)乳腺中導(dǎo)管系統(tǒng)的生長發(fā)育，從而生乳有源，泌乳通暢。當(dāng)產(chǎn)婦感到疼痛下丘腦可刺激催乳素抑制因子，降低泌乳素分泌，抑制泌乳反射，從而延遲泌乳，減少泌乳量，降低乳汁中的蛋白質(zhì)含量。新生兒吸吮乳頭的刺激和擠奶時(shí)人工按摩乳房的刺激，都可影響泌乳活動，組織 乳腺的發(fā)育，切斷乳腺神經(jīng)24?？ㄇ傲兴匕倍∪加址Q為欣母沛，是前列腺2a的一種衍生物，通過提高肌細(xì)胞內(nèi)鈣離子濃度形成誘發(fā)平滑肌收縮

20、的機(jī)制達(dá)到刺激子宮肌層協(xié)調(diào)有力收縮的作用25?？捎行ьA(yù)防產(chǎn)婦產(chǎn)后出血狀況，生物活性明顯高于傳統(tǒng)前列腺素類藥物。剖宮產(chǎn)產(chǎn)婦使用該藥可促進(jìn)子宮肌肉收縮，在胎盤處發(fā)揮止血效果，一旦注入宮體，即可快速通過血液循環(huán)發(fā)揮藥效，一刻鐘后達(dá)到最高藥物濃度26?？ㄘ惪s宮素在臨床用于防治產(chǎn)后出血情況，具有27,28。：（1）起效快，持續(xù)時(shí)間短，需反復(fù)多次用藥；（2）對子宮上段收縮有刺激作用；（3）子宮平滑肌的敏感性與孕激素、雄激素水平密切相關(guān)等特點(diǎn)。對嚴(yán)重的產(chǎn)后出血卡貝縮宮素藥效明顯，需要加用其他子宮收縮劑。但價(jià)錢比其他傳統(tǒng)縮宮素貴，不屬于常規(guī)用藥29,30。研究顯示，單一使用卡前列素氨丁三醇治療剖宮產(chǎn)后出血患者

21、，有效率較低，且患者FIB、D-Dimer檢測值及NO和NOS水平變化不明顯30?？ㄇ傲兴匕倍∪悸?lián)合卡貝縮宮素產(chǎn)婦子宮復(fù)舊有效率93.2%明高于單一使用卡前列素氨丁三醇產(chǎn)婦子宮復(fù)舊有效率74.6%，效果顯著，具有比較意義?？ㄇ傲兴匕倍∪悸?lián)合卡貝縮宮患者中FIB、D-Dimer檢測值及NO、NOS水平均低于單一使用卡前列素氨丁三醇的患者；聯(lián)合用藥者的術(shù)后2h出血量和術(shù)后24h出血量及產(chǎn)后出血率均低于單一用藥者，且宮縮持續(xù)時(shí)間與惡露持續(xù)時(shí)間均明顯高于單一用藥者；聯(lián)合用藥者泌乳時(shí)間低于單一用藥者，產(chǎn)后1d泌乳量評分與產(chǎn)后2d泌乳量評分均顯著升高。由此可見，卡前列素氨丁三醇聯(lián)合卡貝縮宮素治療剖宮產(chǎn)

22、后出血患者效果顯著，具有臨床意義。綜上所述，卡前列素氨丁三醇聯(lián)合卡貝縮宮素對剖宮產(chǎn)后出血患者是一種預(yù)防方案，能夠顯著減少剖宮產(chǎn)產(chǎn)后出血，降低產(chǎn)后出血發(fā)生率，促進(jìn)產(chǎn)后恢復(fù)，值得在臨床上推廣應(yīng)用。參考文獻(xiàn)：1 Straface G,Bassi E,De Santis M,et al. Tranfusion risk: is two-step vaginal delivery a risk for postpartum hemorrhage J. The journal of maternal-fetal & neonatal medicine : the official journal of t

23、he European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2015 ,28 (18 ):2172-2175.2 de la Cruz CZ,Thompson EL,ORourke K,et al. Cesareansectionand the risk of emergency peripartum hysterectomy in high-

24、income countries: a systematic reviewJ. Archives of gynecology and obstetrics ,2015, 292 (6 ):1201-1215.3 Hassan SJ,Wick L,DeJong J. A glance into the hidden burden of maternal morbidity and patterns of management in a Palestinian governmental referral hospitalJ. Women and birth : journal of the Aus

25、tralian College of Midwives ,2015,28 (4 ): 148-156.4 Chen JS,Roberts CL,Simpson JM,et al. Pregnancy Outcomes in Women With Rare Autoimmune DiseasesJ. Arthritis & rheumatology (Hoboken, N.J.) ,2015 ,67 (12 ):3314-3323.5 Macharey G,Ulander VM,Kostev K,er al. Emergency peripartum hysterectomy and risk

26、factors by mode of delivery and obstetric history: a 10-year review from Helsinki University Central HospitalJ. Journal of perinatal medicine ,2015 , 43 (6 ):721-728.6 Barii T,utalo N,Letica L,et al. Rupture of splenic artery aneurysm in primipara five daysaftercesareansection: case report and revie

27、w of the literatureJ. Wiener klinische Wochenschrift ,2015 , 127 (21 ):896-898.7 Helman S,Drukker L,Fruchtman H,et al. Revisit of risk factors for major obstetric hemorrhage: insights from a large medical centerJ. Archives of gynecology and obstetrics, 2015, 292 (4 ):819-828.8 Yamada T,Cho K,Morikaw

28、a M,et al. Intrapartum risk factors for neonatal encephalopathy leading to cerebral palsy in women without apparent sentinel eventsJ. The journal of obstetrics and gynaecology research ,2015,41 (10 ):1520-1525.9 Kaminishi Y,Akutsu H,Sugaya A,et al. Surgical Treatment of Prosthetic Valve Endocarditis

29、J. Kyobu geka. The Japanese journal of thoracic surgery, 2015 ,68 (11 ):907-911.10 Lavaill L,Dussaucy A,Bardonnet K,et al, Automatic detection of cirrhosis in hospitalized patients: a pragmatic experienceJ. European journal of gastroenterology & hepatology ,2016,28 (1 ):74-81.11 Houot M,Ngo Y,Muntea

30、nu M,et al. Systematic review with meta-analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and BJ. Alimentary pharmacology & therapeutics ,2016 ,43 (1 ):16-29.12 Leung DH,Khan M,Minard CG,et al. Aspartate aminotransferase to platelet ratio and fibrosis-4

31、as biomarkers in biopsy-validated pediatric cystic fibrosis liver diseaseJ. Hepatology (Baltimore, Md.) ,2015 ,62 (5 ):1576-1583.13 Abuelo A,Hernndez J,Benedito JL,et al. The importance of the oxidative status of dairy cattle in the periparturient period: revisiting antioxidant supplementationJ. Jou

32、rnal of animal physiology and animal nutrition ,2015 ,99 (6 ):1003-1016.14 Venturelli BC,de Freitas Jnior JE,Takiya CS,et al. Total tract nutrient digestion and milk fatty acid profile of dairy cows fed diets containing different levels of whole raw soya beansJ. Journal of animal physiology and anim

33、al nutrition, 2015,99 (6 ):1149-1160.15 Gessner DK,Most E,Schlegel G,et al. Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acidJ. Journal of animal physiology and animal nutrition ,2015 ,99 (6 ):1039-1046.16 Cui K,Guo XD,Tu Y,et al. Effect of diet

34、ary supplementation of rutin onlactationperformance, ruminal fermentation and metabolism in dairy cowsJ. Journal of animal physiology and animal nutrition ,2015 ,99 (6 ):1065-1073.17 Nagl A,Kneidinger N,Kiik K,et al. Noninvasive monitoring of female reproductive hormone metabolites in the endangered

35、 European mink (Mustela lutreola) J. Theriogenology, 2015 ,84 (9 ):1472-1481.18 Zhang P,Liu J,Tan B,et al. Hypercoagulable state is associated with NF-kappa B activation and increased inflammatory factors in patients with rheumatoid arthritisJ. Xi bao yu fen zi mian yi xue za zhi = Chinese journal o

36、f cellular and molecular immunology ,2016 , 32 (3 ):364-368.19 Choudhary A,Chandra A. Anisotropic structure and dynamics of the solvation shell of a benzene solute in liquid water from ab initio molecular dynamics simulationsJ. Physical chemistry chemical physics : PCCP, 2016,18 (8 ):6132-6145.20 Mu

37、lliner AD,Battle PD,David WI,et al. Dimer-mediated cation diffusion in the stoichiometric ionic conductor Li3NJ. Physical chemistry chemical physics : PCCP ,2016 ,18 (7 ):5605-5613.21 Kasher PR,Schertz KE,Thomas M,et al. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and

38、Variable Developmental Delay with Intellectual DisabilityJ. American journal of human genetics ,2016 ,98 (2 ):363-372.22 Ducarme G,Grange J,Vital M. Expansion dilatation balloons for cervical ripening in obstetric practiceJ. Journal de gynecologie, obstetrique et biologie de la reproduction, 2016, 4

39、5 (2 ):112-119.23 Kalra S,Zargar AH,Jain SM,et al. Diabetes insipidus: The other diabetesJ. Indian journal of endocrinology and metabolism ,2016 , 20 (1 ):9-21.24 Alcorn JL,Green CE,Schmitz J,et al. Effects ofoxytocinon aggressive responding in healthy adult menJ. Behavioural pharmacology, 2017 ,26 (8):798-80425Harrison AJ,Gamsiz ED,Berkowitz IC,et al. Genetic variation in theoxytocinreceptor gene is associated with a social phenotype in autism spectrum di