Vidanagamage R S, Goonewardene I M R
University Obstetrics and Gynaecology Unit, Teaching Hosptial, Galle, Sri Lanka.
Ceylon Med J. 2011 Sep;56(3):91-100. doi: 10.4038/cmj.v56i3.3595.
Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to evaluate the effects on the mother and the fetus when isosorbide mononitrate (ISMN) 40 mg or the sustained release ISMN (ISMN - SR) 60 mg was administered vaginally for preinduction cervical ripening.
A double blind randomised controlled trial. Consecutive women (n=156) with uncomplicated singleton pregnancies between 40 weeks +5 days and 41 weeks' gestation with modified Bishop Scores (MBS) <5 were allocated by stratified (primp/multip) block randomisation to receive ISMN 40 mg, ISMN - SR 60 mg or the placebo vitamin C 100 mg vaginally.
At the commencement of the study the parity and mean age, MBS, pulse rate (PR), systolic and diastolic blood pressure (SBP and DBP), umbilical artery resistance index (RI) and pulsatility index (PI) were similar among the three treatment groups. There was significant increase (p<0.001) of mean MBS by 1.3 (95% CI 0.8, 1.7) in primips and by 1.7 (95% CI 1.3, 2.0) in multips at 6 hours and by 2.4 (95% CI 1.9, 2.7 ) in primips and by 2.3 (95% CI 2.0, 2.6) in multips at 48 hours. Greater proportions of primips (42% with ISMN - SR 60 mg and 31% with ISMN 40 mg, p<0.05) were favourable for induction of labour (IOL) after 48 hours in comparison with the controls (7.6%). Greater proportions of multips (46% with ISMN - SR 60 mg and 40% with ISMN 40 mg, p<0.05) were favourable for IOL after 48 hours in comparison with the controls (16%). A mean increase of PR by 6.7-10.2 bpm (95% CI 5.0 - 12.5, p<0.001) in both ISMN groups at 180 minutes persisted up to 360 minutes. A mean reduction of SBP by 7.3 - 10 mmHg (95% CI = 8.0-11.5, p<0.001) in both ISMN groups at 180 minutes persisted up to 360 mins. No significant change was seen in DBP, RI or PI. Frequency of maternal side effects (mainly headache) were higher in ISMN groups.
When compared with the placebo Vitamin C 100 mg, vaginal ISMN 40 mg and ISMN - SR 60 mg lead to significantly greater cervical ripening after 6 hours and 48 hours respectively. Therefore vaginal ISMN leads to more women becoming favourable for IOL. Vaginal ISMN does not affect placental blood flow but causes headaches and clinically insignificant maternal haemodynamic changes.
一氧化氮供体已被证明可引起宫颈成熟。本研究的目的是评估阴道给予40mg单硝酸异山梨酯（ISMN）或60mg缓释ISMN（ISMN - SR）用于引产术前宫颈成熟时对母亲和胎儿的影响。
一项双盲随机对照试验。将连续入选的156例单胎妊娠、孕周在40周+5天至41周之间、改良Bishop评分（MBS）<5且无并发症的孕妇，按分层（初产妇/经产妇）区组随机化法分为三组，分别经阴道给予40mg ISMN、60mg ISMN - SR或100mg安慰剂维生素C。
研究开始时，三组的产次、平均年龄、MBS、脉搏率（PR）、收缩压和舒张压（SBP和DBP）、脐动脉阻力指数（RI）和搏动指数（PI）相似。6小时时，初产妇的平均MBS显著增加（p<0.001），增加1.3（95%可信区间0.8，1.7），经产妇增加1.7（95%可信区间1.3，2.0）；48小时时，初产妇增加2.4（95%可信区间1.9，2.7），经产妇增加2.3（95%可信区间2.0，2.6）。与对照组（7.6%）相比，48小时后，更多比例的初产妇（60mg ISMN - SR组为42%，40mg ISMN组为31%，p<0.05）适合引产（IOL）。与对照组（16%）相比，48小时后，更多比例的经产妇（60mg ISMN - SR组为46%，40mg ISMN组为40%，p<0.05）适合IOL。两个ISMN组在180分钟时PR平均增加6.7 - 10.2次/分钟（95%可信区间5.0 - 12.5，p<0.001），并持续到360分钟。两个ISMN组在180分钟时SBP平均降低7.3 - 10mmHg（95%可信区间 = 8.0 - 11.5，p<0.001），并持续到360分钟。DBP、RI或PI未见显著变化。ISMN组产妇副作用（主要为头痛）的发生率较高。
与100mg安慰剂维生素C相比，阴道给予40mg ISMN和60mg ISMN - SR分别在6小时和48小时后导致宫颈成熟显著增加。因此，阴道给予ISMN使更多女性适合IOL。阴道给予ISMN不影响胎盘血流，但会引起头痛和临床上无显著意义的产妇血流动力学变化。
