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 due to their high rates of uterine tachysystole.
Both vaginal and oral misoprostol are used for either cervical ripening or labor induction. For labor induction in women at or near term with either prematurely ruptured membranes or a favorable cervix, 100 μg of oral or 25 μg of vaginal misoprostol has similar efficacy compared with intravenous oxytocin. From these studies, evidence supports that oral misoprostol may be superior (Alfirevic, 2014; Hofmeyr, 2010; Lo, 2003). Misoprostol may be associated with a greater rate of uterine tachysystole, particularly at higher doses. Also, induction with PGE1 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. At Parkland Hospital, we administer an initial oral 100-μg dose, which may be repeated after 6 hours for inadequate labor. Six hours after the second dose or in those with tachysystole, an oxytocin infusion is begun, if needed, for hypotonic labor. Döbert and colleagues (2017) have described preliminary use of a misoprostol vaginal insert.
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, the frequency of nonreassuring fetal status or cesarean delivery did not differ between oxytocin and misoprostol.
In many instances, preinduction cervical ripening and labor induction are simply a continuum. Thus, “ripening” can also stimulate labor. If not, induction or augmentation may be continued with solutions of oxytocin given by infusion pump. Its use in augmentation is a key component in the active management of labor, described in Chapter 22 (Labor Management Protocols). With oxytocin use, the American College of Obstetricians and Gynecologists (2016) recommends fetal heart rate and uterine contraction monitoring. Contractions can be monitored either by palpation or by electronic means.
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 is 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 lowers contraction frequency. When oxytocin is stopped, its concentration in plasma rapidly falls because the half-life is approximately 3 to 5 minutes. Seitchik and associates (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 rises rapidly at term (Chap. 24, Intrapartum Surveillance of Uterine Activity).
A 1-mL ampule containing 10 units of oxytocin 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, respectively, 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. In one large Cochrane metaanalysis, oxytocin was compared with expectant management, and fewer women—8 versus 54 percent—failed to deliver vaginally within 24 hours with oxytocin (Alfirevic, 2009). This analysis studied different oxytocin dosing regimens.
Several evidence-based regimens for labor stimulation are now recommended by the American College of Obstetricians and Gynecologists (2016). These and others are shown in Table 26-3. Initially, only variations of low-dose protocols were used in the United States. Subsequently, 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 26-3Various Low- and High-Dose Oxytocin Regimens Used for Labor Induction ||Download (.pdf) TABLE 26-3 Various Low- and High-Dose Oxytocin Regimens Used for Labor Induction
|Regimen ||Starting Dose (mU/min) ||Interval (min) ||Incremental Increase (mU/min) |
|Low-dose ||0.5–1.5 ||15–40 ||1 |
| ||2 ||15 ||4, 8, 12, 16, 20, 25, 30 |
|High-dose ||4 ||15 ||4 |
| ||4.5 ||15–30 ||4.5 |
| ||6 ||20–40a ||6b |
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 lower rates of intrapartum chorioamnionitis or neonatal sepsis. With this protocol, uterine tachysystole was managed by oxytocin discontinuation followed by resumption when indicated and at half the stopping dosage. Thereafter, the dosage was 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 another study, 816 women were randomly assigned for labor induction and 816 for augmentation with incremental oxytocin given at either 1.5 or 4.5 mU/min (Merrill, 1999). Women randomized to the 4.5 mU/min dosage had significantly shorter mean durations of induction-to-second-stage labor and induction-to-delivery times. 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—6 versus 12 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, dosages are employed for either labor induction or augmentation. Although a Cochrane metaanalysis of randomized and quasi-randomized trials comparing high-dose versus low-dose regimens for labor induction at term reported no benefit of higher dosing, the metaanalysis included studies judged to have high potential bias. The authors concluded that the results might be confounded by these poor-quality studies (Budden, 2014).
Interval between Incremental Dosing
Intervals to increase oxytocin doses vary from 15 to 40 minutes (see Table 26-3). Satin and associates (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 doses and increased this every 30 minutes. López-Zeno and associates (1992) used 6 mU/min doses and 15-minute intervals. 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:
The Parkland Hospital protocol uses a starting dose of oxytocin at 6 mU/min, which is increased by 6-mU/min every 40 minutes, and employs flexible dosing based on uterine tachysystole.
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.
Unless the uterus is scarred, uterine rupture associated with oxytocin infusion is rare, even in parous women. Flannelly and associates (1993) reported no cases of 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. A population-based retrospective review from Denmark reported a rupture rate of 3.3 per 100,000 women without prior cesarean, with the highest risk among multiparas (Thisted, 2015). Our experiences from Parkland Hospital are that oxytocin induction and augmentation are associated with uterine rupture (Happe, 2017). During an 8-year period in which there were about 95,000 births, 15 women suffered a primary uterine rupture, and 14 of these cases were associated with oxytocin use. In half of these women, prostaglandins were also given before augmentation with oxytocin.
Oxytocin has amino-acid homology similar to arginine vasopressin and has significant antidiuretic action. When infused at doses of 20 mU/min or more, renal free water clearance drops 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 raising 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 (Chap. 24, Intrapartum Surveillance of Uterine Activity). Caldeyro-Barcia (1950) and Seitchik (1984) with their coworkers found that the mean or median spontaneous uterine contraction pattern between 140 and 150 Montevideo units resulted in progression to vaginal delivery.
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. They later reported that nearly all women in whom active-phase arrest persisted despite oxytocin generated more than 200 Montevideo units (Hauth, 1991). Importantly, despite no labor progression, no adverse maternal or perinatal effects were noted in those ultimately requiring 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 as a completed latent phase and contractions exceeding 200 Montevideo units for more than 2 hours without cervical change. Some 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 dilation of at least 1 cm/hr. In women without progressive cervical dilation 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 (Active-Phase Protraction), these and other studies support the practice of allowing an active-phase arrest of 4 hours (Rouse, 2001).
Zhang and coworkers (2002) analyzed labor duration from 4 cm to complete dilatation in 1329 nulliparas at term. They found that before dilation 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). This is discussed in detail in Chapter 23 (Obstetric Care Consensus Committee). Importantly, however, these studies of data from the Collaborative Perinatal Project included only singleton term gestation with spontaneous onset of labor, vaginal delivery, and a normal perinatal outcome. By excluding abnormal outcomes, cesarean deliveries, and those who were more than 6 cm dilated upon arrival, the above studies that sought to redefine the labor curve have been faulted for introducing biases that limit general use of these findings (Cohen, 2015a,b).
Amniotomy for Induction and Augmentation
Elective amniotomy with the intention of accelerating labor is often performed. Shown 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 the incidences of mild and moderate cord compression patterns were raised following amniotomy, cesarean delivery rates for fetal distress were not higher. Most importantly, there were no adverse perinatal effects.
TABLE 26-4Randomized Clinical Trials of Elective Amniotomy in Early Spontaneous Labor at Term ||Download (.pdf) TABLE 26-4 Randomized Clinical Trials of Elective Amniotomy in Early Spontaneous Labor at Term
| ||Effects of Amniotomy |
|Study ||Number ||Mean Dilation at Amniotomy ||Mean Shortening of Labor ||Need for Oxytocin ||Cesarean Delivery Rate ||Abnormal Tracing ||Neonatal Effects |
|Fraser (1993) ||925 ||<5 cm ||125 min ||None ||Nonea ||None ||None |
|Garite (1993) ||459 ||5.5 cm ||81 min ||Decreased ||None ||Increasedb ||None |
|UK Amniotomy Group (1994) ||1463 ||5.1 cm ||60 min ||None ||None ||NA ||None |
For labor induction, artificial rupture of the membranes—sometimes called surgical induction—can be used and 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) randomly assigned 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 4-hour reduction in labor duration. With early amniotomy, however, the incidence of chorioamnionitis was elevated.
For labor augmentation, amniotomy is commonly performed 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.
Regardless of the indication, amniotomy is associated with a risk of cord prolapse. To minimize this risk, disengagement of the fetal head during amniotomy is avoided. Toward this goal, 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 Stripping for Labor Induction
Labor induction by membrane “stripping” is a frequent practice. Several studies have suggested that membrane stripping is safe and lowers the incidence of postterm pregnancy without consistently raising the incidence of ruptured membranes, infection, or bleeding. Authors of one large metaanalysis found that membrane stripping reduced the number of women remaining undelivered after 41 weeks without elevating 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).