Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Gyetvai K et al., 1999 · Obstet Gynecol
To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
Prescribing Safety · Medication Safety in Pregnancy
Higby K et al., 1993 · Am J Obstet Gynecol
Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.
Hormonal Agents · Progesterone and Progestins
Travis BE et al., 1993 · Pharmacotherapy
Preterm labor is defined as the onset of uterine contractions in a woman who has completed less than 37 weeks of pregnancy. It may be due to maternal, placental, fetal, or idiopathic causes, and it is associated with a number of risk factors. Nondrug measures such as bedrest and hydration have been used alone or in combination with drug therapy to treat the disorder. Pharmacologic (tocolytic) agents include ethanol, progesterone, indomethacin, nifedipine, beta-adrenergic agonists, and magnesium salts. The three most commonly used drugs are ritodrine, terbutaline, and magnesium.
Labor and Birth · Physiologic Birth
Katz Z et al., 1983 · Int J Gynaecol Obstet
The results of combined ritodrine and indomethacine treatment (RI) in premature labor contractions were compared with ritodrine alone (R). One hundred and twenty patients with threatened premature labor in weeks 26-34 were studied. Sixty RI women received 100 mg ritodrine in infusion followed by 60 mg daily orally until 35 weeks and indomethacine 200 mg on the first day of treatment only. The R group included 60 women with identical tocolysis indices, age of pregnancy and anamnestic parameters who received ritodrine only. The mean prolongation index (PI) was 18.2 in the RI group, against 11.5 in the R patients (P less than 0.05). The mean prolongation of pregnancy was 5.6 weeks in the first and 3.6 in the control group (P less than 0.05). Birthweight and Apgar scores were similar in the two groups. In order to examine the possible early closure of the ductus arteriosus due to the indomethacin therapy, echocardiograms were done on all newborn in the RI group: the pre-ejection period and right ventricular ejection time ratio was 0.19-0.26 after delivery and 0.17-0.22 1 month later, which excludes pulmonary diastolic hypertension due to premature closure of the duct. The combined RI treatment is more effective that R alone and does not give rise to any complications in the mother or the fetus.
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