Drug Therapy During Labor and Delivery, Part 2

Gerald G. Briggs; Stephanie R. Wan

Disclosures

Am J Health Syst Pharm. 2006;63(12):1131-1139. 

In This Article

Cervical Ripening and Labor Induction

Labor is defined as an increase in myometrial activity, with uterine contractions and the effacement and dilation of the cervix, resulting in the delivery of the fetus from the uterus.[84] Induction of labor involves artificial stimulation of the uterus, leading to regular or rhythmic contractions, before the spontaneous onset of labor. The goal of labor induction is a vaginal delivery. Induction is indicated when the continuation of pregnancy clearly endangers the well-being of the mother or fetus.[85] Conditions that necessitate labor induction include preeclampsia or eclampsia, fetal death or nonreassuring status, placental abruption (separation of the placenta from the uterine wall), chorioamnionitis, and a pregnancy that has exceeded 42 weeks of duration.[85] Contraindications to labor induction are similar to those for spontaneous labor and vaginal delivery in general: mothers with absolute cephalopelvic disproportion, active genital herpes infection, previous high-vertical hysterotomy or cesarean section with a classic incision, uteroplacental complications such as complete placenta previa (i.e., the placenta covering the cervix) or umbilical cord prolapse, and fetal malpresentation.[85]

Induction of labor occurs in two phases: cervical ripening and induction of contractions. The status of the cervix plays an important role in the success or failure of labor induction. The Bishop scoring system is a tool used to evaluate the clinical cervical state and assigns points for dilation, effacement (thinning), station (degree of engagement of the fetal head in the maternal pelvis), consistency (firm to soft), and position (posterior to anterior) ( Table 1 ).[85,86] Studies have demonstrated that if the total Bishop score is greater than 8, the rate of vaginal delivery after induction is similar to that of spontaneous labor.[85] Low Bishop scores are associated with high rates of failed induction, leading to increased maternal-fetal morbidity and mortality and increased rates of cesarean section. ACOG recommends that the Bishop score be 6 or greater before proceeding with labor induction.[85] A favorable cervical status, and the labor induction that follows, may be achieved by pharmacologic and non-pharmacologic techniques. Non-pharmacologic methods for cervical ripening and induction of contractions include membrane stripping and amniotomy, placement of an intracervical balloon catheter, and insertion of hygroscopic or osmotic dilators. Mechanical dilators, such as laminaria, may cause discomfort to the patient and may increase infection. While they are equally as effective as pharmacologic agents, they may be indicated in patients for whom pharmacologic agents are contraindicated or unavailable due to supply or cost.[84,85]

Oxytocin and prostaglandins (i.e., misoprostol and dinoprostone) are used for labor induction. The dosages, routes of administration, and cost of these agents are summarized in Table 2 and Table 3 . Maternal vital signs, fetal heart rate, and uterine activity should be continuously monitored. Knowledge of the drugs' half-lives and duration of action is important in anticipating both their effectiveness and potential adverse effects.[87]

Misoprostol, a prostaglandin E1 analogue, is used both for cervical ripening and induction. Its only FDA-approved indication is for the prevention of gastric ulcers induced by nonsteroidal antiinflammatory drugs (NSAIDs); however, it is widely used in obstetrics for preinduction cervical ripening, stimulation of uterine contractions, treatment of postpartum hemorrhage in the presence of uterine atony, and as an adjunct to mifepristone in medical abortion.[88] When used for cervical ripening and labor induction, the 100-µg tablet is broken in halves and in quarters to achieve the 50- and 25-µg doses, respectively. Intravaginal misoprostol has been reported to be either superior or comparable to dinoprostone gel, and the benefits of misoprostol over dinoprostone include ease of administration, stability, storage (misoprostol may be stored at room temperature; dinoprostone requires sterile handling and refrigeration), and cost.[85]

A general complication associated with prostaglandins is uterine hyperstimulation. This is defined as either a series of single contractions lasting 2 minutes or more or a contraction frequency of five or more in 10 minutes.[85] Fetal heart rate abnormalities may also occur. Higher rates of hyperstimulation have been reported with intravaginal dinoprostone inserts when compared with the intracervical gel; removing the vaginal insert typically reverses the effect. Higher doses (e.g., ≥50 µg) and shorter administration intervals (e.g., every three hours) of misoprostol are also associated with greater rates of hyperstimulation compared with lower doses (e.g., 25 µg) and longer administration intervals (e.g., every six hours). Administration of a ß-sympathomimetic agent (e.g., terbutaline sulfate 0.125-0.25 mg subcutaneously or i.m.) usually resolves hyperstimulation by decreasing the frequency of uterine contractions. Unresolved hyperstimulation may result in uterine rupture or placental abruption. In patients with prior cesarean section, misoprostol should be avoided due to the increased risk for incisional uterine rupture. Other adverse effects and general precautions with prostaglandin use include gastrointestinal effects and relative precautions when used in patients with glaucoma or pulmonary disease.[85,87,88]

Oxytocin is a potent endogenous uterotonic agent.[87] Given exogenously, it is used for both artificial induction and augmentation of labor. Oxytocin increases the frequency, force, and duration of uterine contractions. Its uterine effects increase throughout pregnancy, starting at 20 weeks and leveling out at 34 weeks until term, when uterine sensitivity to oxytocin increases dramatically due to increases in the number of oxytocin receptors at term and during labor. Maternal parity, stage of cervical advancement, and gestational age are important predictors in individual oxytocin dose response. Both low- and high-dosage oxytocin regimens administered by continuous infusion are used; balancing oxytocin dosage selection and frequency of incremental rate increase requires special attention to the potential for uterine hyperstimulation or fetal distress, while still effectively promoting strong uterine contractions to shorten labor, decrease cesarean deliveries, and reduce perinatal morbidity.[85] One protocol recommended by ACOG initiates oxytocin at 0.5-2 milliunits/min, increasing by 1-2 milliunits/min every 30-60 minutes and using a cervical dilation rate of 1 cm/hr to gauge adequate progression of active labor.[85] The maximum doses of oxytocin range from approximately 20 milliunits/min for augmentation of delivery to 40 milliunits/min for induction of labor.[85,87] Oxytocin is generally prepared as 10 units diluted in 1000 mL of isotonic (electrolyte containing) solution of 10 milliunits/mL. Adverse effects of oxytocin include water intoxication (a rare effect secondary to its antidiuretic effect at large dosages), cardiovascular effects (premature ventricular contractions, hypotension, and mild and transient hypertension), and uterine hypertonicity.[87]

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