General Obstetrics and Gynecology: Obstetrics
Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: A randomized controlled trial to determine effects on maternal and fetal hemodynamics

https://doi.org/10.1067/mob.2001.111797Get rights and content

Abstract

Objective: Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term. Study Design: We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes. Results: Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination–only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination–only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination–only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index. Conclusions: Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant. (Am J Obstet Gynecol 2001;184:958-64.)

Section snippets

Methods

The study was performed at the Glasgow Royal Maternity Hospital between August 1998 and July 1999. Primigravid women who were to undergo induction of labor were asked to participate in the study. Approval was granted by the local ethics committee. Written informed consent was obtained from each participant before recruitment.

Women who wished to participate in the study were assessed by vaginal examination. Assessment of the cervix included an assessment of consistency, length, dilatation,

Results

By the end of the 1-year study period, 38 women had been recruited to the study. Two of the women recruited were excluded from the study after a treatment had been allocated but before its administration. One of these women was excluded because of breech presentation and the other because treatment administration was delayed and, in the interval, spontaneous labor ensued. These women were excluded from the analysis.

Thirteen women received isosorbide mononitrate, 20 mg. These women had a median

Comment

Nitric oxide, also known as endothelium-dependent relaxing factor, is an important biologic mediator in human beings.13, 14 Nitric oxide is a small, highly reactive free radical gas with a half-life of 4 seconds. Nitric oxide is synthesized from the amino acid L -arginine by the action of the enzyme nitric oxide synthase. There are 3 isoforms of the enzyme—neuronal, inducible, and endothelial (forms I, II, and III). Nitric oxide exerts its effects in part by stimulation of guanylate cyclase and

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