What are the investigational medications for dystocia (dysfunctional labor)?

From the Guidelines

Investigational medications for dysfunctional labor should prioritize oxytocin infusion as the first-line treatment, with a recommended dosage and administration protocol, to enhance uterine contractions and promote acceptable progress in cervical dilatation, as evidenced by the most recent study 1.

Key Considerations

• The optimal response to uterotonic stimulation is enhancement of uterine contractions and acceptable progress in cervical dilatation, signaling a good prognosis for safe vaginal delivery 1.
• If postarrest dilatation does not occur, proceeding to cesarean delivery (CD) is a better and safer option, especially if evidence of cephalopelvic disproportion (CPD) emerges 1.
• Oxytocin receptor antagonists, calcium channel blockers, prostaglandin receptor modulators, Rho-kinase inhibitors, and nitric oxide donors are being investigated for their potential in managing dysfunctional labor, but their use is off-label and requires careful patient selection and monitoring 1.

Treatment Options

• Oxytocin infusion is the primary treatment for dysfunctional labor, with a recommended protocol of administration to enhance uterine contractions and promote cervical dilatation 1.
• Artificial rupture of membranes may be considered, but its effectiveness is not supported by objective evidence, and it should only be performed for overriding reasons, such as applying fetal monitoring scalp electrodes or inserting an intrauterine pressure transducer 1.
• Cesarean delivery is a safer option if evidence of CPD is found or if it cannot be ruled out with a reasonable degree of certainty, due to the increased risk of damage to the mother and fetus 1.

Patient Selection and Monitoring

• Clinicians should carefully select patients for investigational medications and obtain informed consent, as these medications are not FDA-approved for dysfunctional labor 1.
• Close monitoring of maternal and fetal effects is essential when using investigational medications, and clinicians should be aware of the potential risks and benefits associated with each treatment option 1.

From the FDA Drug Label

PRECAUTIONS General All patients receiving intravenous oxytocin must be under continuous observation by trained personnel with a thorough knowledge of the drug and qualified to identify complications. When properly administered, oxytocin should stimulate uterine contractions similar to those seen in normal labor Except in unusual circumstances, oxytocin should not be administered in the following conditions: prematurity, borderline cephalopelvic disproportion, previous major surgery on the cervix or uterus including Caesarean section, overdistention of the uterus, grand multiparity or invasive cervical carcinoma DOSAGE AND ADMINISTRATION Dosage of oxytocin is determined by uterine response. The following dosage information is based upon the various regimens and indications in general use. Induction or Stimulation of Labor Intravenous infusion (drip method) is the only acceptable method of administration for the induction or stimulation of labor. Patients in whom oxytocic drugs are generally contraindicated or where prolonged contractions of the uterus are considered inappropriate, such as: o cases with a history of cesarean section or major uterine surgery o cases in which cephalopelvic disproportion is present o cases in which there is a history of difficult labor and/or traumatic delivery o grand multiparae with six or more previous term pregnancies cases with non-vertex presentation o cases with hyperactive or hypertonic uterine patterns o cases of fetal distress where delivery is not imminent o in obstetric emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention

Investigational medications for dysfunctional labor are oxytocin (IV) and dinoprostone (PV).

• Oxytocin (IV) is used for induction or stimulation of labor and should be administered under continuous observation by trained personnel with a thorough knowledge of the drug.
• Dinoprostone (PV) is used in patients where oxytocic drugs are not contraindicated and prolonged contractions of the uterus are considered appropriate. The decision to use these medications can only be made by carefully weighing the potential benefits against the rare but definite potential for the drug to produce hypertonicity or tetanic spasm 2, 2, 3.

From the Research

Investigational Medications for Dysfunctional Labor

• The ideal agent for induction of labor when the cervix is unripe is unknown, but several prostaglandin derivatives are currently available, including misoprostol and dinoprostone 4.
• Misoprostol has been used with good success for induction of labor and is a cost-effective option compared to dinoprostone 4.
• A prospective, randomized trial comparing the efficacy and safety of misoprostol and dinoprostone for induction of labor found that misoprostol resulted in a faster delivery time and less need for oxytocin augmentation 4.

Comparison of Misoprostol and Dinoprostone

• A systematic review and meta-analysis of 53 randomized controlled trials found that misoprostol was more effective at inducing labor than dinoprostone, but may be less safe due to a higher incidence of uterine hyperstimulation and tachysystole 5.
• Another systematic review and meta-analysis found that intravaginal misoprostol was an effective and safe alternative to dinoprostone for labor induction at term, requiring less oxytocin augmentation 6.
• A comparison of oxytocin and vaginal dinoprostone for labor induction found that both agents had similar effects on delivery outcomes and safety concerns in pregnant women with a gestational age of 36 weeks or more 7.

Safety and Efficacy of Misoprostol and Dinoprostone

• The incidence of fetal distress, cesarean section, and adverse neonatal outcomes was similar between misoprostol and dinoprostone groups in several studies 4, 5, 6.
• However, misoprostol was associated with a higher incidence of uterine hyperstimulation and tachysystole compared to dinoprostone 4, 5.
• The Apgar score at one and five minutes was similar between misoprostol and dinoprostone groups in some studies, but was lower in the misoprostol group in others 4, 6.