Randomized trial of two beta-mimetic drugs (ritodrine and fenoterol) in acute intra-partum tocolysis

Summary The uterine inhibitory effect and potential maternal and fetal side effects of two -mimetic compounds, ritodrine hydrochloride and fenoterol hydrobromide, were compared in a randomized trial. The drugs were administered by intravenous infusion to 24 healthy term nulliparous women during effective first-stage labour; each of them received fenoterol (1, 2, or 4 µg/min) or ritodrine (100, 200, or 400 µg/min). There was no difference between the drugs in the intensity of the uterine inhibition. However, for a similar inhibitory effect, the duration of tocolysis was longer after ritodrine. During the intrapartum and neonatal periods, neither compound induced any change in the fetal parameters investigated, and their effects on maternal parameters were comparable.     

黄体酮与盐酸利托君联合治疗先兆早产的临床研究

目的:探讨黄体酮与盐酸利托君联合治疗先兆早产的临床效果。方法:选择2017年1月~2018年12月某院收治的96例先兆早产患者作为研究对象,以随机数表法将其分为对照组与研究组各48例。对照组应用盐酸利托君治疗,研究组在此基础上联合黄体酮治疗,评价两组患者保胎成功率、药物起效时间、妊娠延长时间以及药物不良反应。结果:研究组保胎成功率95.83%高于对照组84.78%(P<0.05);研究组药物起效时间与住院时间均低于对照组(P<0.05),妊娠延长时间高于对照组(P<0.05);两组不良反应发生率对比差异无统计学意义(P>0.05)。结论:黄体酮与盐酸利托君联合治疗先兆早产起效快,保胎效果佳。     

Magnesium sulfate and ritodrine hydrochloride: systemic and uterine hemodynamic effects

Effects of magnesium sulfate and ritodrine hydrochloride on cardiovascular physiologic characteristics were studied in 70 human subjects treated for preterm labor. Systemic and uterine hemodynamic effects were investigated in five pregnant rhesus monkeys. Systolic blood pressure was minimally affected by either agent. Diastolic pressure, while not affected by magnesium sulfate, decreased 26.3% during ritodrine therapy. Maternal and fetal heart rates were minimally affected by magnesium sulfate. Ritodrine increased maternal and fetal heart rates significantly. In the monkeys, magnesium sulfate increased uterine and placental blood flows (by the microsphere technique) but failed to alter cardiac output. Ritodrine produced an increase in cardiac output but decreased perfusion pressure. Placental blood flow decreased by an average of 27.6%. Ritodrine would therefore seem contraindicated with a compromised fetal environment. Magnesium sulfate, by not altering perfusion pressure, may have a beneficial effect on uterine hemodynamics. These specific and distinct differences in cardiovascular and hemodynamic effects should be considered when either magnesium sulfate or ritodrine is selected as a tocolytic agent.     

The influence of ritodrine on glucose and insulin blood levels after oral glucose loading in the last three months of normal pregnancy

By a t-test for paired observations the influence of ritodrine, a β-sympathicomimetic drug which is administered as a tocolytic, on the blood glucose concentrations and the insulin secretion of women in their last 3 months of pregnancy, whose metabolism was normal, was demonstrated by means of the oral glucose tolerance test. Upon administration of ritodrine, the insulin levels as well as the mean glucose values significantly exceed the results obtained from the standard glucose tolerance test. In 12 out of 21 patients abnormally high blood glucose levels were encountered following additional administration of ritodrine.     

Contribution of nitric oxide to beta2-adrenoceptor mediated vasodilatation in human forearm arterial vasculature

AIMS: beta2-adrenoceptor agonists are generally considered to produce endothelium independent vasodilatation through adenylate cyclase. We determined whether nitric oxide contributes to beta2-adrenoceptor vasodilatation in human arterial vasculature. METHODS: Forearm blood flow responses to brachial intra-arterial infusions of ritodrine (2.5-50 microg min(-1)), a selective beta2-adrenoceptor agonist, were determined in 24 healthy, normotensive subjects (mean age 22 years, 5F) on two occasions with initial and concomitant administration of L-NMMA (800 microg min(-1)), an NO synthase inhibitor, or noradrenaline (5-30 ng min(-1)), a control constrictor not affecting basal NO activity. Responses to the endothelium dependent vasodilator scrotonin (n = 6) and an endothelium independent vasodilator GTN (n = 9) were also determined. RESULTS: Maximal dilatation to ritodrine during L-NMMA infusion (310+/-32%; mean+/-s.e.mean) was reduced compared to that during noradrenaline infusion (417+/-41%, P<0.05), as were summary responses (1023+/-101 vs 1415+/-130; P<0.05). Responses to GTN were unaffected by L-NMMA compared to noradrenaline; max 177+/-26 vs 169+/-20%, 95% CI for difference -33,48; P=0.68; summary response 361+/-51 vs 396+/-37, 95% CI -142,71; P=0.46. Dilator responses to serotonin were reduced by L-NMMA; max 64+/-20 vs 163+/-26%, P<0.01; summary response 129+/-36 vs 293+/-60; P<0.05) and to a greater extent than ritodrine (58+/-7 vs 25+/-14%, P<0.05). CONCLUSIONS: beta2-adrenoceptor mediated vasodilatation in the human forearm has an NO mediated component. The underlying mechanism for this effect is unclear, but flow mediated vasodilatation is unlikely to be responsible.     

The safety of tocolytics used for the inhibition of preterm labour

ABSTRACT

Introduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%.

Areas covered: Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use.

Expert opinion: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β₂-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.     

Anaesthesia for Caesarean section in a parturient with quintuplet gestation,pulmonary oedema and thrombocytopaenia

The case of a 32-year-old parturient with a quintuplet pregnancy is described. The pregnancy had been complicated by premature labour which was treated with ritodrine tocolysis. Betamethasone was administered to hasten fetal lung maturation. The ritodrine therapy was complicated with fluid overload and pulmonary oedema requiring intravenous diuretic treatment. The patient presented urgently for Caesarean section, with fluid overload and worsening thrombocytopaenia. Life-threatening pulmonary oedema was manifest in the immediate preinduction period, following insertion of a pulmonary artery catheter and surgery was delayed to improve the mother's condition with intravenous diuretic therapy. Induction was carried out with the patient in the sitting position, with cricoid pressure maintained to protect the airway as the patient was lowered to a wedged, supine position. Intravenous nitroglycerin was used to control blood pressure. Low pressure mask-bag ventilation was utilized to maintain oxygen saturation and the patient was intubated and ventilated with positive end-expiratory pressure. Positive pressure ventilation was continued for 24 hours postoperatively. The perioperative course is reviewed and followed by a discussion of the anaesthetic considerations for multiple gestation pregnancies.     

盐酸利托君联合黄体酮治疗先兆早产的疗效观察

目的对盐酸利托君联合黄体酮治疗先兆早产的临床疗效进行回顾性研究。方法对应用硫酸镁、单独应用盐酸利托君和应用盐酸利托君联合黄体酮等三种疗法治疗先兆早产的疗效进行回顾性分析,每组各30例,对患者用药后的保胎效果、显效时间、延长妊娠时间等进行比较。结果盐酸利托君组的保胎有效率为83．3％,联合用药组为80％,两组显著优于硫酸镁组的60％（P〈0．05）。盐酸利托君组和联合用药组在保胎有效率、延长妊娠时间、显效时间等方面无显著差异（P〉0．05）,但均优于硫酸镁组（P〈0．05）。结论盐酸利托君是治疗先兆早产的安全有效方法,值得临床推广应用。盐酸利托君联合黄体酮对孕中、晚期保胎治疗的协同作用不显著。     

Recent pharmacological advances in the treatment of preterm membrane rupture,labour and delivery

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17α-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, β₂-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.     

保胎灵联合盐酸利托君治疗先兆早产的临床疗效观察

目的探讨保胎灵联合盐酸利托君治疗先兆早产的临床疗效。方法选取2008年7月至2010年12月于本院确诊的198例先兆早产孕妇为研究对象。按照治疗方案将其分为观察组(保胎灵+盐酸利托君,n=96)和对照组(单用盐酸利托君,n=102)。观察两种方案治疗先兆早产的显效时间、治疗时间、住院时间、保胎成功率、延长孕龄时间和保胎至≥35孕周分娩率、产后出血量/率、新生儿预后及不良反应发生率等的作用。两组孕妇年龄、孕周、孕次、产次、宫缩及宫颈扩张情况比较,差异无显著意义(P>0.05)。(本研究遵循的程序符合本院人体试验委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书)。结果两组显效时间、治疗时间及住院时间比较,差异均有显著意义(P<0.05)。观察组保胎成功率、延长孕龄时间和保胎至≥35孕周分娩率均明显高于对照组,差异有显著意义(P<0.05)。两组产后出血量、产后出血率比较,差异无显著意义(P>0.05)。观察组新生儿预后较对照组好(P<0.05),不良反应发生率低于对照组,差异有显著意义(P<0.05)。结论保胎灵联合盐酸利托君治疗先兆早产可提高盐酸利托君疗效,改善新生儿预后,降低盐酸利托君不良反应,但是否值得临床进一步推广,尚需大样本、多中心的前瞻性随机对照研究证实。