Randomised, double-blind, placebo controlled pilot study assessing nitroglycerin as a tocolytic. Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor. Glyceryl trinitrate and ritodrine in tocolysis: an international multicenter randomized study. GTN Preterm Labour Investigation Group. Corticotropin-releasing hormone: a biochemical predictor of preterm delivery in a pilot randomized trial of the treatment of preterm labor.
Thirty-three women in preterm labour were randomised in a double-blind fashion to receive either transdermal nitroglycerin (n = 17) or placebo (n = 16). Both groups had significant (P < 0.001) change in the cervix prior to randomisation. The primary outcome measure was delivery within 48 hours of randomisation. Fewer women randomised to nitroglycerin treatment (6/17) were delivered within 48 hours, compared with the placebo treatment (10/16) (RR 0.56, 95% CI 0.27 to 1.19). This pilot study lends support to two case series published that suggest that transdermal nitroglycerin may be promising as a safe, effective means for tocolysis. To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.
                Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.
                Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.
                Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor. To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics.
                Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat.
                Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) -10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference -11%; 95% CI -24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate.
                We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine. We assessed the ability of maternal plasma corticotropin-releasing hormone measurements to predict preterm delivery in the setting of a pilot study comparing transdermal glyceryl trinitrate with standard beta-mimetic therapy for preterm labor and to determine the effect of these tocolytics on maternal plasma corticotropin-releasing hormone concentrations.
                Twenty-six consecutive patients with preterm labor were randomized to tocolytic treatment with transdermal glyceryl trinitrate (n=13) or intravenous albuterol (n=13).
                Plasma corticotropin-releasing hormone immunoreactivity levels were higher in women who were delivered within 7 days (41.4+/-13.5 pmol/L) than in those continuing to term (14.2+/-2.4 pmol/L, p=0.011) and were not altered by treatment. Two women in each of the treatment groups delivered within 7 days of the initiation of treatment, two women in the glyceryl trinitrate group were changed to albuterol because of persistence of contractions. Glyceryl trinitrate treatment was associated with significantly fewer maternal side effects. Neither treatment altered umbilical artery Doppler ultrasonographic findings.
                Transdermal glyceryl trinitrate is better tolerated than intravenous albuterol but may be no more efficacious than albuterol for the treatment of preterm labor. Biologic markers such as plasma corticotropin-releasing hormone levels may be an important method of identifying women at high risk of preterm delivery.
There is currently insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labour.
[Note: The 26 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]