PREINDUCTION CERVICAL RIPENING
METHODS OF INDUCTION AND AUGMENTATION
AMNIOTOMY FOR INDUCTION AND AUGMENTATION
Induction implies stimulation of contractions before the spontaneous onset of labor, with or without ruptured membranes. When the cervix is closed and uneffaced, labor induction will often commence with cervical ripening, a process that generally employs prostaglandins to soften and open the cervix.
Augmentation refers to enhancement of spontaneous contractions that are considered inadequate because of failed cervical dilation and fetal descent. In the United States, the incidence of labor induction more than doubled from 9.5 percent in 1991 to 23.2 percent in 2011 (Martin, 2013). The incidence is variable between practices. At Parkland Hospital approximately 35 percent of labors are induced or augmented. By comparison, at the University of Alabama at Birmingham Hospital, labor is induced in approximately 20 percent of women, and another 35 percent are given oxytocin for augmentation—a total of 55 percent. This chapter includes an overview of indications for labor induction and augmentation and a description of various techniques to effect preinduction cervical ripening.
Induction is indicated when the benefits to either mother or fetus outweigh those of pregnancy continuation. The more common indications include membrane rupture without labor, gestational hypertension, oligohydramnios, nonreassuring fetal status, postterm pregnancy, and various maternal medical conditions such as chronic hypertension and diabetes (American College of Obstetricians and Gynecologists, 2013b).
Methods to induce or augment labor are contraindicated by most conditions that preclude spontaneous labor or delivery. The few maternal contraindications are related to prior uterine incision type, contracted or distorted pelvic anatomy, abnormally implanted placentas, and uncommon conditions such as active genital herpes infection or cervical cancer. Fetal factors include appreciable macrosomia, severe hydrocephalus, malpresentation, or nonreassuring fetal status.
Oxytocin has been used for decades to induce or augment labor. Other effective methods include prostaglandins, such as misoprostol and dinoprostone, and mechanical methods that encompass stripping of membranes, artificial rupture of membranes, extraamnionic saline infusion, transcervical balloons, and hygroscopic cervical dilators. Importantly, and as recommended in Guidelines for Perinatal Care, each obstetrical department should have its own written protocols that describe administration of these methods for labor induction and augmentation (American Academy of Pediatrics and American College of Obstetricians and Gynecologists, 2012).
Maternal complications associated with labor induction consist of cesarean delivery, chorioamnionitis, uterine scar rupture, and postpartum hemorrhage from uterine atony.
Cesarean Delivery Rate
This is especially increased in nulliparas undergoing induction (Luthy, 2004; Yeast, 1999). Indeed, several investigators have reported a two- to threefold increased risk (Hoffman, 2003; Maslow, 2000; Smith, 2003). Moreover, these rates are inversely related with cervical favorability at induction, that is, the Bishop score (Vahratian, 2005; Vrouenraets, 2005). The increased risk for cesarean delivery with labor induction does not appear to be lowered with preinduction cervical ripening in the nullipara with an unfavorable cervix (Mercer, 2005). In fact, the cesarean delivery rate following elective induction was significantly increased even in women with a Bishop score of 7 or greater compared with that in those with spontaneous labor (Hamar, 2001). Station and position of the fetal vertex may also affect success rates. For example, in nulliparas at > 41 weeks’ gestation and with an unengaged vertex, the cesarean delivery rate was increased 12-fold compared with that in women with an engaged fetal vertex (Shin, 2004).
The premise that elective labor induction increases the risk of cesarean delivery has been questioned (Macones, 2009). Many studies have compared women undergoing labor induction to those laboring spontaneously. However, using women undergoing expectant management, Osmundson and colleagues (2010, 2011) reported similar cesarean delivery rates in more than 4000 women undergoing elective induction between 39 and nearly 41 weeks with or without a favorable cervix. Currently, this subject remains unresolved.
Amniotomy is often selected to augment labor (p. 531). Women whose labor is managed with amniotomy have an increased incidence of chorioamnionitis compared with those in spontaneous labor (American College of Obstetricians and Gynecologists, 2013a).
Rupture of a Prior Uterine Incision
Uterine rupture during labor in women with a history of prior uterine surgery can be catastrophic (Chap. 31, p. 613). Some of these risks were quantified by Lydon-Rochelle and associates (2001), who reported that the uterine rupture risk is increased threefold for women in spontaneous labor with a uterine scar. With oxytocin labor induction without prostaglandins, the risk was fivefold increased, and with prostaglandins, it was strikingly increased 15.6-fold. The Maternal-Fetal Medicine Units Network also reported a threefold increased risk of uterine scar rupture with oxytocin, and this was even higher when prostaglandins were also used (Landon, 2004). The American College of Obstetricians and Gynecologists (2013d) recommends against the use of misoprostol for preinduction cervical ripening or labor induction in women with a prior uterine scar (Chap. 31, p. 615).
Postpartum hemorrhage from uterine atony is more common in women undergoing induction or augmentation. And, atony with intractable hemorrhage, especially during cesarean delivery, is a frequent indication for peripartum hysterectomy (Shellhaas, 2009). In a study from Parkland Hospital, labor induction was associated with 17 percent of 553 emergency peripartum hysterectomies (Hernandez, 2013). In the United States, Bateman and coworkers (2012) reported that the postpartum hysterectomy rate increased 15 percent between 1994 and 2007. This was largely attributable to increased rates of atony associated with more medical labor inductions and more primary and repeat cesarean deliveries. Finally, elective induction was associated with more than a threefold increased rate of hysterectomy in the analysis by Bailit and colleagues (2010).
Elective Labor Induction
There can be no doubt that elective induction for convenience has become more prevalent. In the United States between 1991 and 2006, rates of early term labor induction increased significantly for all race and ethnicity groups (Murthy, 2011). This was highest for non-Hispanic white women in 2006. In this group, the rate was 20.5 percent if there was either diabetes or hypertension and was 9 percent for women without these indications. Clark and coworkers (2009) reported data from 14,955 deliveries at 37 weeks or greater. They noted that 32 percent were elective deliveries, and 19 percent were elective labor inductions.
The American College of Obstetricians and Gynecologists (2013b) does not endorse this widespread practice. Occasional exceptions might include logistical and other reasons such as a risk of rapid labor, a woman who lives a long distance from the hospital, or psychosocial indications. We are also of the opinion that routine elective induction at term is not justified because of the increased risks for adverse maternal outcomes. Elective delivery before 39 completed weeks is also associated with significant and appreciable adverse neonatal morbidity (Chiossi, 2013; Clark, 2009; Tita, 2009). If elective induction is considered at term, inherent risks must be discussed, informed consent obtained, and guidelines followed as promulgated by the American College of Obstetricians and Gynecologists (2013b), which are detailed in Chapter 31 (p. 610).
Guidelines to discourage elective inductions have been described by Fisch (2009) and Oshiro (2013) and their associates. Both groups reported significant decreases in elective delivery rates following guideline initiation. Tanne (2013) surveyed more than 800 United States hospitals and reported that efforts to reduce early term deliveries are succeeding.
Factors Affecting Successful Induction
Several factors increase or decrease the ability of labor induction to achieve vaginal delivery. Favorable factors include multiparity, body mass index (BMI) < 30, favorable cervix, and birthweight < 3500 g (Peregrine, 2006; Pevzner, 2009). For both nulliparas and multiparas, Kominiarek and colleagues (2011) found that labor duration to reach the active phase and to complete dilatation was adversely affected by a higher BMI.
In many cases, the uterus is simply poorly prepared for labor. One example is an “unripe cervix.” Indeed, investigators with the Consortium on Safe Labor reported that elective induction resulted in vaginal delivery in 97 percent of multiparas and 76 percent of nulliparas, but that induction was more often successful with a ripe cervix (Laughon, 2012a). The increased cesarean delivery risk associated with induction is likely also strongly influenced by the induction attempt duration, especially with an unfavorable cervix (Spong, 2012). Simon and Grobman (2005) concluded that a latent phase as long as 18 hours during induction allowed most of these women to achieve a vaginal delivery without a significantly increased risk of maternal or neonatal morbidity. Rouse and associates (2000) recommend a minimum of 12 hours of uterine stimulation with oxytocin after membrane rupture.
PREINDUCTION CERVICAL RIPENING
As noted, the condition of the cervix—described as cervical “ripeness” or “favorability”—is important to successful labor induction. That said, at least some estimates of favorability are highly subjective. In either case, there are pharmacological and mechanical methods that can enhance cervical favorability—also termed preinduction cervical ripening.
Some of the techniques described may have benefits when compared with oxytocin induction alone (Table 26-1). Some are also quite successful for initiating labor. That said, few data support the premise that any of these techniques results in a reduced cesarean delivery rate or in less maternal or neonatal morbidity compared with that in women in whom these methods are not used.
TABLE 26-1. Some Commonly Used Regimens for Preinduction Cervical Ripening and/or Labor Induction
One quantifiable method used to predict labor induction outcomes is the score described by Bishop (1964) and presented in Table 26-2. As favorability or Bishop score decreases, the rate of induction to effect vaginal delivery also declines. A Bishop score of 9 conveys a high likelihood for a successful induction. Put another way, most practitioners would consider that a woman whose cervix is 2-cm dilated, 80-percent effaced, soft, and midposition and with the fetal occiput at –1 station would have a successful labor induction. For research purposes, a Bishop score of 4 or less identifies an unfavorable cervix and may be an indication for cervical ripening.
TABLE 26-2. Bishop Scoring System Used for Assessment of Inducibility
Laughon and coworkers (2011) attempted to simplify the Bishop score by performing a regression analysis on 5610 singleton, uncomplicated deliveries by nulliparas between 370/7 and 416/7 weeks. Only cervical dilation, station, and effacement were significantly associated with successful vaginal delivery. Thus, a simplified Bishop score, which incorporated only these three parameters, had a similar or improved positive- or negative- predictive value compared with that of the original Bishop score.
Transvaginal sonographic measurement of cervical length has been evaluated as a Bishop score alternative. Hatfield and associates (2007) performed a metaanalysis of 20 trials in which cervical length was used to predict successful induction. Because of study criteria heterogeneity—including the definition of “successful induction”—the authors concluded that the question remains unanswered. Both this study and the one by Uzun and colleagues (2013) found that sonographically determined cervical length was not superior to the Bishop score for predicting induction success.
Unfortunately, women frequently have an indication for induction but also have an unfavorable cervix. Thus, considerable research has been directed toward techniques to “ripen” the cervix before uterine contraction stimulation. Importantly, more often than not, techniques used to improve cervical favorability also stimulate contractions and thereby aid subsequent labor induction or augmentation. Techniques most commonly used for preinduction cervical ripening and induction include several prostaglandin analogues.
Dinoprostone is a synthetic analogue of prostaglandin E2. It is commercially available in three forms: a gel, a time-release vaginal insert, and a 10-mg suppository. The gel and time-release vaginal insert formulations are indicated only for cervical ripening before labor induction. However, the 10-mg suppository is indicated for pregnancy termination between 12 and 20 weeks and for evacuation of the uterus after fetal demise up to 28 weeks.
Local application of dinoprostone is commonly used for cervical ripening (American College of Obstetricians and Gynecologists, 2013b). Its gel form—Prepidil—is available in a 2.5-mL syringe for an intracervical application of 0.5 mg of dinoprostone. With the woman supine, the tip of a prefilled syringe is placed intracervically, and the gel is deposited just below the internal cervical os. After application, the woman remains reclined for at least 30 minutes. Doses may be repeated every 6 hours, with a maximum of three doses recommended in 24 hours.
A 10-mg dinoprostone vaginal insert—Cervidil—is also approved for cervical ripening. This is a thin, flat, rectangular polymeric wafer held within a small, white, mesh polyester sac (Fig. 26-1). The sac has a long attached tail to allow easy removal from the vagina. The insert provides slower release of medication—0.3 mg/hr—than the gel form. Cervidil is used as a single dose placed transversely in the posterior vaginal fornix. Lubricant should be used sparingly, if at all, because it can coat the device and hinder dinoprostone release. Following insertion, the woman should remain recumbent for at least 2 hours. The insert is removed after 12 hours or with labor onset and at least 30 minutes before the administration of oxytocin.
FIGURE 26-1 Cervidil vaginal insert contains 10 mg of dinoprostone designed to release approximately 0.3 mg/hr during a 10-hour period.
Most metaanalyses of dinoprostone efficacy report a reduced time to delivery within 24 hours. However, they do not consistently show a reduction in the cesarean delivery rate. Kelly and coworkers (2009) provided a Cochrane review of 63 trials and 10,441 women given vaginal prostaglandins or either placebo or no treatment. These investigators reported a higher vaginal delivery rate within 24 hours when prostaglandins were used. They also found that cesarean delivery rates were unchanged. Similar results were reported after another Cochrane review of intracervical dinoprostone gel by Boulvain and associates (2008). Compared with placebo or no treatment, a reduced risk of cesarean delivery was found only in a subgroup of women with an unfavorable cervix and intact membranes. Finally, the Foley catheter versus vaginal prostaglandin E2 gel for induction of labor at term (PROBAAT trials) were unblinded, randomized trials comparing these two options (Jozwiak, 2011, 2013a, 2014). There was no difference in cesarean delivery rate, a finding consistent with accompanying metaanalyses.
Side Effects. Uterine tachysystole has been reported to follow vaginally administered prostaglandin E2 in 1 to 5 percent of women (Hawkins, 2012). Although definitions of uterine activity vary among studies, most use the definition recommended by the American College of Obstetricians and Gynecologists (2013c):
1. Uterine tachysystole is defined as > 5 contractions in a 10-minute period. It should always be qualified by the presence or absence of fetal heart rate abnormalities.
2. Uterine hypertonus, hyperstimulation, and hypercontractility are terms no longer defined, and their use is not recommended.
Because uterine tachysystole associated with fetal compromise may develop when prostaglandins are used with preexisting spontaneous labor, such use is not recommended. If tachysystole follows the 10-mg insert, its removal by pulling on the tail of the surrounding net sac will usually reverse this effect. Irrigation to remove the gel preparation has not been shown to be helpful.
The manufacturers recommend caution when these preparations are used in women with ruptured membranes. Caution is also recommended when they are used in women with glaucoma or asthma. In a review of 189 women with asthma, however, dinoprostone was not associated with asthma worsening or exacerbation (Towers, 2004). Other contraindications listed by the manufacturers include a history of dinoprostone hypersensitivity, suspicion of fetal compromise or cephalopelvic disproportion, unexplained vaginal bleeding, women already receiving oxytocin, those with six or more previous term pregnancies, those with a contraindication to vaginal delivery, or women with a contraindication to oxytocin or who may be endangered by prolonged uterine contractions, for example, those with a history of cesarean delivery or uterine surgery.
Administration. Prostaglandin E2 preparations should only be administered in or near the delivery suite. Moreover, uterine activity and fetal heart rate should be monitored (American College of Obstetricians and Gynecologists, 2013b). These guidelines stem from the risk of uterine tachysystole. When contractions begin, they are usually apparent in the first hour and show peak activity in the first 4 hours. According to manufacturer guidelines, oxytocin induction that follows prostaglandin use for cervical ripening should be delayed for 6 to 12 hours following prostaglandin E2 gel administration or for at least 30 minutes after removal of the vaginal insert.
Misoprostol—Cytotec—is a synthetic prostaglandin E1 that is approved as a 100- or 200-μg tablet for peptic ulcer prevention. It has been used “off label” for preinduction cervical ripening and may be administered orally or vaginally. The tablets are stable at room temperature. Although widespread, the off-label use of misoprostol has been controversial (Wagner, 2005; Weeks, 2005). Specifically, G. D. Searle & Company (Cullen, 2000) notified physicians that misoprostol is not approved for labor induction or abortion. At the same time, however, the American College of Obstetricians and Gynecologists (2013b) reaffirmed its recommendation for use of the drug because of proven safety and efficacy. It currently is the preferred prostaglandin for cervical ripening at Parkland Hospital.
Vaginal Administration. Numerous studies have reported equivalent or superior efficacy for cervical ripening or labor induction with vaginally administered misoprostol tablets compared with intracervical or intravaginal prostaglandin E2. A metaanalysis of 121 trials also confirmed these findings (Hofmeyr, 2010). Compared with oxytocin or with intravaginal or intracervical dinoprostone, misoprostol increased the vaginal delivery rate within 24 hours. Moreover, although the uterine tachysystole rate increased, this did not affect cesarean delivery rates. Compared with dinoprostone, misoprostol decreased the need for oxytocin induction, but it increased the frequency of meconium-stained amnionic fluid. Higher doses of misoprostol are associated with a decreased need for oxytocin but more uterine tachysystole with and without fetal heart rate changes. The American College of Obstetricians and Gynecologists (2013b) recommends the 25-μg vaginal dose—a fourth of a 100-μg tablet. The drug is evenly distributed among these quartered tablets.
Wing and colleagues (2013) recently described use of a vaginal polymer insert containing 200 μg of PGE1. They compared its efficacy with 10-mg dinoprostone inserts, and preliminary observations are favorable.
Oral Administration. Prostaglandin E1 tablets are also effective when given orally. Ho and coworkers (2010) performed a randomized controlled trial comparing titrated oral misoprostol with oxytocin. They found similar rates of vaginal delivery and side effects. In a metaanalysis of nine trials including nearly 3000 women, however, there were reported improvements in various outcomes with oral misoprostol (Kundodyiwa, 2009). In particular, there was a significantly lower cesarean delivery rate for the five trials comparing oral misoprostol with dinoprostone—relative risk 0.82. For the two trials comparing oral with vaginal misoprostol, oral misoprostol was associated with a lower rate of uterine tachysystole with fetal heart rate changes, but there were no significant differences with respect to rates of cesarean delivery or other outcomes.
Nitric Oxide Donors
Several findings have led to a search for clinical agents that stimulate nitric oxide (NO) production locally (Chanrachakul, 2000a). This is because nitric oxide is likely a mediator of cervical ripening (Chap. 21, p. 423). Also, cervical nitric oxide metabolite concentrations are increased at the beginning of uterine contractions. Last, cervical nitric oxide production is very low in postterm pregnancy (Väisänen-Tommiska, 2003, 2004).
Bullarbo and colleagues (2007) reviewed rationale and use of two nitric oxide donors, isosorbide mononitrate and glyceryl trinitrate. Isosorbide mononitrate induces cervical cyclooxygenase 2 (COX-2), and it also brings about cervical ultrastructure rearrangement similar to that seen with spontaneous cervical ripening (Ekerhovd, 2002, 2003). Despite this, clinical trials have not shown nitric oxide donors to be as effective as prostaglandin E2 for cervical ripening (Chanrachakul, 2000b; Osman, 2006). Moreover, the addition of isosorbide mononitrate to either dinoprostone or misoprostol did not enhance cervical ripening either in early or term pregnancy nor did it shorten time to vaginal delivery (Collingham, 2010; Ledingham, 2001; Wölfler, 2006). A metaanalysis of 10 trials including 1889 women concluded that nitric oxide donors do not appear to be useful for cervical ripening during labor induction (Kelly, 2011).
These include transcervical placement of a Foley catheter with or without extraamnionic saline infusion, hygroscopic cervical dilators, and membrane stripping. In a recent metaanalysis of 71 randomized trials including 9722 women, Jozwiak and associates (2012) reported that mechanical techniques reduced the risk of uterine tachysystole compared with prostaglandins, although cesarean delivery rates were unchanged. Trials comparing mechanical techniques with oxytocin found a lower rate of cesarean delivery with mechanical methods. Trials comparing mechanical techniques with dinoprostone found a higher rate of multiparous women undelivered at 24 hours with mechanical techniques. Another metaanalysis done to compare Foley catheter placement with intravaginal dinoprostone inserts also found similar rates of cesarean delivery and less frequent uterine tachysystole (Jozwiak, 2013a).
Generally, these techniques are only used when the cervix is unfavorable because the catheter tends to come out as the cervix opens. In most cases, a Foley catheter is placed through the internal cervical os, and downward tension is created by taping the catheter to the thigh (Mei-Dan, 2014). A modification of this—extraamnionic saline infusion (EASI)—consists of a constant saline infusion through the catheter into the space between the internal os and placental membranes (Fig. 26-2). Karjane and coworkers (2006) reported that chorioamnionitis was significantly less frequent when infusion was done compared with no infusion—6 versus 16 percent. A systematic review and metaanalysis of 30 trials found that Foley catheter induction alone compared with prostaglandins resulted in higher infection rates unless saline was infused (Heinemann, 2008).
FIGURE 26-2 Extraamnionic saline infusion (EASI) through a 26F Foley catheter that is placed through the cervix. The 30-mL balloon is inflated with saline and pulled snugly against the internal os, and the catheter is taped to the thigh. Room-temperature normal saline is infused through the catheter port of the Foley at 30 or 40 mL/hour by intravenous infusion pump.
Most studies of transcervical catheters do not show a reduction in the cesarean delivery rate compared with prostaglandins. Cromi and colleagues (2012) compared a double-tipped Foley catheter and the dinoprostone vaginal insert. They found higher rates of delivery within 24 hours with the mechanical technique, but no differences in the cesarean delivery rates. The PROBAAT trials, in which cervical ripening with a Foley catheter was compared with vaginal dinoprostone gel, dinoprostone vaginal inserts, and vaginal misoprostol, reported similar outcomes between the mechanical technique and the prostaglandin agents. Also, fewer overall cases of cardiotocographic changes were seen in the mechanical technique group (Jozwiak, 2011, 2013a, 2014; Wang, 2014).
Hygroscopic Cervical Dilators
Cervical dilatation can be accomplished using hygroscopic osmotic cervical dilators, as described for early pregnancy termination (Chap. 18, p. 365). These mechanical dilators have been successfully used for more than 40 years when inserted before pregnancy termination. They have also been used for cervical ripening before labor induction. Intuitive concerns of ascending infection have not been verified. Thus, their use appears to be safe, although anaphylaxis has rarely followed laminaria insertion (Lichtenberg, 2004). Dilators are attractive because of their low cost. However, placement generally requires a speculum and positioning of the woman on an examination table, which can be cumbersome and uncomfortable. A handful of studies performed in the 1990s compared hygroscopic cervical dilators and prostaglandins. There were few benefits of this mechanical technique other than cost.
METHODS OF INDUCTION AND AUGMENTATION
Labor induction has primarily been effected with the use of amniotomy, prostaglandins, and oxytocin, alone or in combination. Because preinduction cervical ripening frequently eventuates in labor, studies to determine induction efficacy for some of these agents have produced sometimes confusing results. The use of prostaglandins for labor augmentation has generally been considered experimental.
As discussed on page 527, both vaginal and oral misoprostol are used for either cervical ripening or labor induction. Hofmeyr and associates (2010) performed a Cochrane systematic review of agents for labor induction. They reported that vaginal misoprostol, followed by oxytocin if needed, compared with oxytocin alone resulted in fewer failures within 24 hours. As expected, prostaglandin use led to a higher incidence of uterine tachysystole, but cesarean delivery rates were similar.
It appears that 100 μg of oral or 25 μg of vaginal misoprostol are similar in efficacy compared with intravenous oxytocin for labor induction in women at or near term with either prematurely ruptured membranes or a favorable cervix (Lin, 2005; Lo, 2003). Misoprostol may be associated with an increased rate of uterine tachysystole, particularly at higher doses. Also, induction with prostaglandin E1 may prove ineffective and require subsequent induction or augmentation with oxytocin. Thus, although there are trade-offs regarding the risks, costs, and ease of administration of each drug, either is suitable for labor induction.
For labor augmentation, results of a randomized controlled trial showed oral misoprostol, 75 μg given at 4-hour intervals for a maximum of two doses, to be safe and effective (Bleich, 2011). The 75-μg dose was based on a previous dose-finding study (Villano, 2011). Although there was more uterine tachysystole among women with labor augmented with misoprostol, there were no significant differences in the frequency of nonreassuring fetal status or cesarean delivery.
As discussed, in most instances, preinduction cervical ripening and labor induction are simply a continuum. Thus, “ripening” will also stimulate labor. If not, induction or augmentation may be continued with solutions of oxytocin given by infusion pump. Synthetic oxytocin is one of the most frequently used medications in the United States. It was the first polypeptide hormone synthesized, an achievement for which the 1955 Nobel Prize in chemistry was awarded (du Vigneaud, 1953). Oxytocin may be used for labor induction or for augmentation. With oxytocin use, the American College of Obstetricians and Gynecologists (2013b) recommends fetal heart rate and contraction monitoring similar to that for any high-risk pregnancy. Contractions can be monitored either by palpation or by electronic means (Chap. 24, p. 497).
Intravenous Oxytocin Administration
The goal of induction or augmentation is to effect uterine activity sufficient to produce cervical change and fetal descent, while avoiding development of a nonreassuring fetal status. In general, oxytocin should be discontinued if the number of contractions persists with a frequency of more than five in a 10-minute period or more than seven in a 15-minute period or with a persistent nonreassuring fetal heart rate pattern. Oxytocin discontinuation nearly always rapidly decreases contraction frequency. When oxytocin is stopped, its concentration in plasma rapidly falls because the half-life is approximately 3 to 5 minutes. Seitchik and coworkers (1984) found that the uterus contracts within 3 to 5 minutes of beginning an oxytocin infusion and that a plasma steady state is reached in 40 minutes. Response is highly variable and depends on preexisting uterine activity, cervical status, pregnancy duration, and individual biological differences. Caldeyro-Barcia and Poseiro (1960) reported that the uterine response to oxytocin increases from 20 to 30 weeks’ gestation and increases rapidly at term (Chap. 24, p. 498).
Oxytocin Dosage. A 1-mL ampule containing 10 units usually is diluted into 1000 mL of a crystalloid solution and administered by infusion pump. A typical infusate consists of 10 or 20 units, which is 10,000 or 20,000 mU or one or two 1-mL vials, mixed into 1000 mL of lactated Ringer solution. This mixture results in an oxytocin concentration of 10 or 20 mU/mL, respectively. To avoid bolus administration, the infusion should be inserted into the main intravenous line close to the venipuncture site.
Oxytocin is generally very successful when used to stimulate labor. A Cochrane metaanalysis of 12 trials involving 12,819 women comparing oxytocin with expectant management reported that fewer women—8 versus 54 percent—failed to deliver vaginally within 24 hours when oxytocin was used (Alfirevic, 2009). This metaanalysis studied different oxytocin dosing regimens. A smaller metaanalysis of four trials involving 660 women and comparing high-dose and low-dose oxytocin regimens reported that high-dose regimens were associated with reduced length of labor and cesarean delivery rate and with a concomitant increased spontaneous vaginal delivery rate (Mori, 2011).
As a result of numerous studies, several regimens for labor stimulation are now recommended by the American College of Obstetricians and Gynecologists (2013a). These and others are shown in Table 26-3. Initially, only variations of low-dose protocols were used in the United States. Then O’Driscoll and colleagues (1984) described their Dublin protocol for the active management of labor that called for oxytocin at a starting dosage of 6 mU/min and advanced in 6-mU/min increments. Subsequent comparative trials during the 1990s studied high-dose—4 to 6 mU/min—versus conventional low-dose—0.5 to 1.5 mU/min—regimens, both for labor induction and for augmentation.
TABLE 26-3. Various Low- and High-Dose Oxytocin Regimens Used for Labor Induction
From Parkland Hospital, Satin and associates (1992) evaluated an oxytocin regimen using an initial and incremental dosage of 6 mU/min compared with one using 1 mU/min. Increases at 20-minute intervals were provided as needed. Among 1112 women undergoing induction, the 6-mU/min regimen resulted in a shorter mean admission-to-delivery time, fewer failed inductions, and no cases of neonatal sepsis. Among 1676 women who had labor augmentation, those who received the 6-mU/min regimen had a shorter duration-to-delivery time, fewer forceps deliveries, fewer cesarean deliveries for dystocia, and decreased rates of intrapartum chorioamnionitis or neonatal sepsis. With this protocol, uterine tachysystole is managed by oxytocin discontinuation followed by resumption when indicated and at half the stopping dosage. Thereafter, the dosage is increased at 3 mU/min when appropriate, instead of the usual 6-mU/min increase used for women without tachysystole. No adverse neonatal effects were observed.
Xenakis and coworkers (1995) reported benefits using an incremental oxytocin regimen starting at 4 mU/min. In a comparative study of 1307 women by Merrill and Zlatnik (1999), 816 women were randomized for labor induction and 816 for augmentation with incremental oxytocin given at either 1.5 or 4.5 mU/min. Women randomized to the 4.5 mU/min dosage had significantly decreased mean durations of induction-to-second-stage labor and induction-to-delivery. Nulliparas randomized to the 4.5 mU/min dosage had a significantly lower cesarean delivery rate for dystocia compared with those given 1.5 mU/min dosage—5.9 versus 11.9 percent.
Thus, benefits favor higher-dose regimens of 4.5 to 6 mU/min compared with lower dosages of 0.5 to 1.5 mU/min. In 1990 at Parkland Hospital, routine use of the 6-mU/min oxytocin beginning and incremental dosage was incorporated and continues through today. In other labor units, a 2-mU/min beginning and incremental oxytocin regimen is preferred and administered. With either regimen, these dosages are employed for either labor induction or augmentation.
Interval between Incremental Dosing
Intervals to increase oxytocin doses vary from 15 to 40 minutes as shown in Table 26-3. Satin and colleagues (1994) addressed this aspect with a 6-mU/min regimen providing increases at either 20- or 40-minute intervals. Women assigned to the 20-minute interval regimen for labor augmentation had a significantly reduced cesarean delivery rate for dystocia compared with that for the 40-minute interval regimen—8 versus 12 percent. As perhaps expected, uterine tachysystole was significantly more frequent with the 20-minute escalation regimen.
Other investigators reported even more frequent incremental increases. Frigoletto (1995) and Xenakis (1995) and their coworkers gave oxytocin at 4 mU/min with increases as needed every 15 minutes. Merrill and Zlatnik (1999) started with 4.5 mU/min, with increases every 30 minutes. López-Zeno and associates (1992) began at 6 mU/min with increases every 15 minutes. Thus, there are several acceptable oxytocin protocols that at least appear dissimilar. But a comparison of protocols from two institutions indicates that this is not so:
1. The Parkland Hospital protocol calls for a starting dose of oxytocin at 6 mU/min and with 6-mU/min increases every 40 minutes, but it employs flexible dosing based on uterine tachysystole.
2. The University of Alabama at Birmingham Hospital protocol begins oxytocin at 2 mU/min and increases it as needed every 15 minutes to 4, 8, 12, 16, 20, 25, and 30 mU/min.
Thus, although the regimens at first appear disparate, if there is no uterine activity, either regimen is delivering 12 mU/min by 45 minutes into the infusion.
The maximal effective dose of oxytocin to achieve adequate contractions in all women is different. Wen and colleagues (2001) studied 1151 consecutive nulliparas and found that the likelihood of progression to vaginal delivery decreased at and beyond an oxytocin dosage of 36 mU/min. Still, at a dosage of 72 mU/min, half of the nulliparas were delivered vaginally. Thus, if contractions are not adequate—less than 200 Montevideo units—and if the fetal status is reassuring and labor has arrested, an oxytocin infusion dose greater than 48 mU/min has no apparent risks.
Risks versus Benefits
Unless the uterus is scarred, uterine rupture associated with oxytocin infusion is rare, even in parous women (Chap. 41, p. 790). Flannelly and associates (1993) reported no uterine ruptures, with or without oxytocin, in 27,829 nulliparas. There were eight instances of overt uterine rupture during labor in 48,718 parous women. Only one of these was associated with oxytocin use.
Oxytocin has amino-acid homology similar to arginine vasopressin. Because of this, it has significant antidiuretic action, and when infused at doses of 20 mU/min or more, renal free water clearance decreases markedly. If aqueous fluids are infused in appreciable amounts along with oxytocin, water intoxication can lead to convulsions, coma, and even death. In general, if oxytocin is to be administered in high doses for a considerable period of time, its concentration should be increased rather than increasing the flow rate of a more dilute solution. Consideration also should be given to use of crystalloids—either normal saline or lactated Ringer solution.
Uterine Contraction Pressures
Contraction forces in spontaneously laboring women range from 90 to 390 Montevideo units. As described in Chapter 24 (p. 498), the latter are calculated by subtracting the baseline uterine pressure from the peak contraction pressure for each contraction in a 10-minute window. The pressures generated by each contraction are then summed. Caldeyro-Barcia (1950) and Seitchik (1984) with their coworkers found that the mean or median spontaneous uterine contraction pattern resulting in a progression to a vaginal delivery was between 140 and 150 Montevideo units.
In the management of active-phase arrest, and with no contraindication to intravenous oxytocin, decisions must be made with knowledge of the safe upper range of uterine activity. Hauth and colleagues (1986) described an effective and safe protocol for oxytocin augmentation for active-phase arrest. With it, more than 90 percent of women achieved an average of at least 200 to 225 Montevideo units. Hauth and associates (1991) later reported that nearly all women in whom active-phase arrest persisted despite oxytocin generated more than 200 Montevideo units. Importantly, despite no labor progression, there were no adverse maternal or perinatal effects in those undergoing cesarean delivery. There are no data regarding safety and efficacy of contraction patterns in women with a prior cesarean delivery, with twins, or with an overdistended uterus.
First-stage arrest of labor is defined by the American College of Obstetricians and Gynecologists (2013a) as a completed latent phase along with contractions exceeding 200 Montevideo units for more than 2 hours without cervical change. Some investigators have attempted to define a more accurate duration for active-phase arrest (Spong, 2012). Arulkumaran and coworkers (1987) extended the 2-hour limit to 4 hours and reported a 1.3-percent cesarean delivery rate in women who continued to have adequate contractions and progressive cervical dilatation of at least 1 cm/hr. In women without progressive cervical dilatation who were allowed another 4 hours of labor, half required cesarean delivery.
Rouse and colleagues (1999) prospectively managed 542 women at term with active-phase arrest and no other complications. Their protocol was to achieve a sustained pattern of at least 200 Montevideo units for a minimum of 4 hours. This time frame was extended to 6 hours if activity of 200 Montevideo units or greater could not be sustained. Almost 92 percent of these women were delivered vaginally. As discussed in Chapter 23 (p. 459), these and other studies support the practice of allowing an active-phase arrest of 4 hours (Rouse, 2001; Solheim, 2009).
Zhang and coworkers (2002) analyzed labor duration from 4 cm to complete dilatation in 1329 nulliparas at term. They found that before dilatation of 7 cm was reached, lack of progress for more than 2 hours was not uncommon in those who delivered vaginally. Alexander and associates (2002) reported that epidural analgesia prolonged active labor by 1 hour compared with duration of the active phase as defined by Friedman (1955). Consideration of these changes in the management of labor, especially in nulliparas, may safely reduce the cesarean delivery rate.
As data have accrued, investigators have increasingly questioned the thresholds for labor arrest disorders established by Friedman and others in the 1960s. In particular, investigators with the Consortium on Safe Labor reported that half of cases of dystocia after labor induction occurred before 6 cm of cervical dilation (Boyle, 2013; Zhang, 2010c). Even for women with spontaneous labor, these researchers found that active-phase labor was more likely to occur at 6 cm, and after slow progress between 4 and 6 cm (Zhang, 2010a). Additionally, they reported that a 2-hour threshold for diagnosing arrest disorders may be too brief when cervical dilation is < 6 cm (Zhang, 2010b). It was also shown that the duration of first-stage labor was more than 2 hours longer than had been reported using data from the Collaborative Perinatal Project (Laughon, 2012b).
Amniotomy for Induction and Augmentation
A common indication for artificial rupture of the membranes—surgical amniotomy—includes the need for direct monitoring of the fetal heart rate or uterine contractions or both. During amniotomy, to minimize cord prolapse risk, dislodgement of the fetal head is avoided. For this, fundal or suprapubic pressure or both may be helpful. Some clinicians prefer to rupture membranes during a contraction. If the vertex is not well applied to the lower uterine segment, a gradual egress of amnionic fluid can sometimes be accomplished by several membrane punctures with a 26-gauge needle held with a ring forceps and with direct visualization using a vaginal speculum. In many of these, however, membranes tear and fluid is lost rapidly. Because of the risk of cord prolapse or rarely abruption, the fetal heart rate is assessed before and immediately after amniotomy.
Membrane rupture with the intention of accelerating labor is often performed. In the investigations presented in Table 26-4, amniotomy at approximately 5-cm dilation accelerated spontaneous labor by 1 to 1½ hours. Importantly, neither the need for oxytocin stimulation nor the overall cesarean delivery rate was increased. Although mild and moderate cord compression patterns were increased following amniotomy, cesarean delivery rates for fetal distress were not increased. Most importantly, there were no adverse perinatal effects.
TABLE 26-4. Randomized Clinical Trials of Elective Amniotomy in Early Spontaneous Labor at Term
Artificial rupture of the membranes—sometimes called surgical induction—can be used to induce labor, and it always implies a commitment to delivery. The main disadvantage of amniotomy used alone for labor induction is the unpredictable and occasionally long interval until labor onset. That said, in a randomized trial, Bakos and Bäckström (1987) found that amniotomy alone or combined with oxytocin was superior to oxytocin alone. Mercer and colleagues (1995) randomized 209 women undergoing oxytocin induction to either early amniotomy at 1 to 2 cm or late amniotomy at 5 cm. Early amniotomy was associated with a significant 4-hour reduction in labor duration. With early amniotomy, however, there was an increased incidence of chorioamnionitis.
It is common practice to perform amniotomy when labor is abnormally slow. Rouse and associates (1994) found that amniotomy with oxytocin augmentation for arrested active-phase labor shortened the time to delivery by 44 minutes compared with that of oxytocin alone. Although amniotomy did not alter the delivery route, one drawback was that it significantly increased the incidence of chorioamnionitis. The American College of Obstetricians and Gynecologists (2013a) recommends the use of amniotomy to enhance progress in active labor, but cautions that this may increase the risks of infection and maternal fever.
Membrane Stripping for Labor Induction
Labor induction by membrane “stripping” is a frequent practice. Several studies have suggested that membrane stripping is safe and decreases the incidence of postterm pregnancy without consistently increasing the incidence of ruptured membranes, infection, or bleeding. Authors of a metaanalysis of 22 trials including 2797 women reported that membrane stripping reduced the number of women remaining undelivered after 41 weeks without increasing the infection risk. They concluded that eight women would need to undergo membrane stripping to avoid one labor induction. Downsides are discomfort and associated bleeding (Boulvain, 2005).
ACTIVE MANAGEMENT OF LABOR
This term describes a codified approach to the management of labor, which is discussed in detail in Chapter 22 (p. 452).
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