Over the past decade, the rate of induction has risen steadily in the United States to an all-time high of 18% of all pregnancies requiring induction of labor in 1999.1 Many women who require induction of labor present with an “unripe” cervix.2 This has been associated with a longer duration in labor and higher rates of failed induction, requiring cesarean delivery.3–5 Performing preinduction cervical ripening appears to improve induction success in these patients.6–8 However, this often adds significantly to the time necessary for the induction of labor. Increasing induction rates and an often lengthy induction process have overburdened many already busy labor and delivery suites and most likely contributed to rising costs.
Moving preinduction cervical ripening from an inpatient to an outpatient setting appears to decrease cost significantly.9 Furthermore, 50% of all patients requiring the induction of labor may be eligible for outpatient cervical ripening.9 Multiple studies have attempted to perform cervical ripening in the outpatient setting.10–16 All but one of these trials used PGE2 preparations. These reports have used differing doses and preparations of PGE2 with varying results, which led the American College of Obstetricians and Gynecologists to recommend that larger controlled trials be performed before outpatient use of PGE2 can be recommended.17
Preinduction cervical ripening can be performed with either hormonal or mechanical methods. Hormonal methods are most commonly used in the United States. Currently there are two agents approved by the Federal Drug Administration, of which both have dinoprostone (PGE2) as their active form. We have shown previously that a mechanical method, the Foley catheter, had significant advantages over a dinoprostone gel Prepidil (Pharmacia & Upjohn, Kalamazoo, MI) for preinduction cervical ripening.18 Although it is approved to prevent the occurrence of gastric ulcers in patients taking nonsteroidal anti-inflammatory drugs, misoprostol (Cytotec; Searle Canada, Oakville, Ontario, Canada), a PGE1 analogue has been shown recently to be effective as an induction agent.19 In a randomized trial comparing misoprostol to the Foley catheter for preinduction cervical ripening, we found that they were equally efficacious, but found an increased risk of meconium passage and uterine contractile abnormalities in the misoprostol group.20
The Foley catheter, because of its effectiveness and apparent safety, appears to be a good option for outpatient preinduction cervical ripening. However, in our previous trials, the Foley catheter was frequently checked and tension readjusted as needed. Although we could understand the economic benefits of outpatient cervical ripening and the social advantages for patients, we could not be assured similar clinical results with patients managing the catheter as an outpatient. Furthermore, we were concerned that women may need to return to the hospital as a result of anxiety or questions caused from having to care for the catheter, thus negating any benefits in outpatient ripening.
In an effort to determine if cervical ripening with the Foley catheter was feasible and effective in the outpatient setting, we performed a randomized prospective comparison of inpatient to outpatient use in a carefully selected low-risk population.
MATERIALS AND METHODS
After approval from the Institutional Review Board and Human Experimentation Committee at the Christiana Hospital and Thomas Jefferson University Hospital, we began a prospective, randomized trial from May 1998 to December 1999. All deliveries occurred at Christiana Hospital or Thomas Jefferson University Hospital. Although Christiana Hospital and Thomas Jefferson University Hospital serve as tertiary referral hospitals, patients who were transferred from an outlying hospital were not eligible for the trial. Patients were eligible if their attending physician had requested preinduction cervical ripening using the Foley catheter. The trial was explained to the patient, and, if they agreed to the potential randomization to outpatient ripening, they were offered entry. Women who were greater than or equal to 37 weeks' gestation with a single vertex pregnancy and a Bishop score of no more than 5 were included. Exclusion criteria included the following: placenta previa, low-lying placenta, undiagnosed vaginal bleeding, preeclampsia, fetal anomaly, intrauterine growth restriction, Rh isoimmunization, fetal demise, rupture of the membranes, maternal heart disease, known latex allergy, active genital herpes infection, previous transfundal uterine surgery, poor or no access to a telephone, excessive distance (more than 30 minutes) from the hospital, and/or unreliable transportation.
Upon presentation to the pre-admission area, an initial assessment was conducted and a history and physical examination completed by the house staff. The procedure for Foley catheter placement was explained to the patient. Before placement of the Foley, a digital exam was performed and a Bishop score assigned by the attending or senior-level resident. A No. 16 Foley catheter with a 30-mL balloon was inserted into the endocervical canal under direct visualization by sterile speculum exam. The Foley catheter was advanced to or past the internal os, and the balloon was filled with 30 mL of sterile water. The catheter was then placed on gentle traction by taping the end of the catheter to the medial portion of the thigh. A nonstress test was performed after Foley catheter placement. If the fetal heart rate was reactive and there was no sign of uterine tachysystole (six or more contractions in two consecutive 10-minute time periods), uterine hypertonus (a contraction lasting over 3 minutes), or uterine hyperstimulation (uterine tachysystole or hypertonus with a nonreassuring fetal heart rate), the patient was randomized. If the test was nonreactive or nonreassuring, they were not offered randomization. An amniotic fluid index was also performed, and, if less than the fifth percentile,21 the patient was not offered entry.
Randomization was performed by a computer-generated random number table and placed in sequentially numbered envelopes.
Patients randomized to the inpatient arm of the trial were admitted to the labor and delivery suite and allowed to ambulate with hourly fetal heart rate assessment until they became tired or until painful contractions ensued. The Foley catheter was checked every 2–4 hours for extrusion and adjusted to maintain steady gentle traction. Oxytocin was administered when the Foley catheter was extruded.
Patients who were randomized to the outpatient arm of the trial were given detailed written and oral instructions before discharge. The written discharge instructions included a telephone number for 24-hour telephone access to a physician or nurse for any questions or concerns. The patients were instructed to notify their doctor for heavy vaginal bleeding, rupture of the membranes, painful uterine contractions every 5 minutes or less, severe abdominal discomfort or decreased movement of the baby. Patients were informed that extrusion of the Foley might occur while at home. They were asked to record time of extrusion and that this was expected and normal. If they were not experiencing any of the aforementioned symptoms, they were asked to dispose of the catheter and remain at home. They were then asked to return to the hospital at 6:00 AM the following morning.
Upon presentation to the labor and delivery suite, the status of the Foley catheter was evaluated. Patients presenting with the Foley in place were treated by initiating oxytocin until the Foley was extruded. If the Foley was extruded, the patient was immediately started on intravenous oxytocin. No other induction agent could be used. The oxytocin management and timing of rupture of the membranes was left to the discretion of the attending physician.
Because the intent of this trial was to evaluate the effectiveness of preinduction cervical ripening in the outpatient setting versus the inpatient setting, the primary outcome variable was change in Bishop score. This was defined as the change from initial Bishop score assignment to the Bishop score at extrusion of the Foley catheter or at the time when the outpatient group presented for induction of labor at 6:00 AM. To detect a difference of at least 1 in change in Bishop score between the groups maintaining a power of 80% with an α level of .05 and using a variance of 1.75 from our previous trial,18 49 women were needed in each group. We chose a change in Bishop score of at least 1, because we felt any less change would not be clinically relevant. Secondary outcome measures included maximum dose and total time on oxytocin, delivery route, time for preinduction cervical ripening, total induction time, total time spent in the hospital, neonatal intensive care unit admission, and 5-minute Apgar score. The Student t test, the Fisher exact test, and χ2 were used where appropriate to compare the two groups.
One hundred eleven women were entered into the trial. Sixty-one women were randomized to the outpatient group and 50 women to the inpatient group. All patients remained in their original allocation group. Thirty-one patients were not offered entrance into the trial: twenty-three for oligohydramnios and eight for bishop score of over 5. The reason for induction is described in Table 1. No differences in maternal age, gravidity, gestational age at entry, or amniotic fluid index were noted between the two groups (Table 2). There were three women in the outpatient group and four women in the inpatient group who had a previous cesarean delivery.
The rate of epidural anesthesia was not statistically different between the groups (97.7% compared with 97.6%; P = .96). There were no significant differences in neonatal outcomes between the groups, and the fetal weights were not different between the groups (Table 3).
The primary outcome variable was change in Bishop score (Table 3). This was not different between the groups (3.0 versus 3.0; P = .74). In addition, Bishop score after preinduction cervical ripening (Bishop II) was not different between the groups (Table 3). The maximum dose of oxytocin and total time on oxytocin were not different between the groups (Table 3).
Because the amount of time spent in the hospital often translates into patient charges, we examined the amount of time in the hospital between the groups. On average, the outpatient group avoided 9.6 hours of time in the hospital. Because the outpatient group was asked not to return to the hospital until a predetermined time, the outpatient group spent significantly more time in preinduction cervical ripening, defined as time between Foley catheter placement and Foley catheter extrusion (Table 3). However, the total time for induction of labor (placement of Foley catheter until delivery) was not different between the groups (Table 3).
There were no significant differences between the groups for 1-minute Apgar score, 5-minute Apgar score, or cord pH.
The difference in preinduction cervical ripening time is most likely attributable to the following two factors: 1) patients in the outpatient group were asked to recall extrusion times, as opposed to the inpatient group, in which the extrusion time was documented by the labor nurse; 2) when the women in the outpatient group returned the following morning for induction, the Foley was occasionally found in the vagina upon examination. The inpatient group was checked frequently for extrusion of the Foley.
The inpatient group had a higher rate of cesarean delivery, but this was not statistically significant (Table 3). A power analysis was performed to determine the number of patients needed to detect a difference in cesarean delivery between the groups, maintaining an 80% power and an α error of .05. Two hundred eighty-four patients would be needed in each group to reach adequate power.
Patients were asked to describe their discomfort during the preinduction cervical ripening phase using a visual analogue test. This was based on a scale from 1 to 10, with 1 being no discomfort or minimal discomfort, and 10 being the worst pain imaginable. The outpatient group reported a mean discomfort level of 4.8 ± 2.4 and the inpatient group of 3.9 ± 2.3 (P = .16). Most of the discomfort was reported immediately after placement of the Foley catheter and was described by the patients as mild to moderate cramping.
Five of 61 (8%) women in the outpatient group returned to the hospital before 6 AM the following morning either for rupture of membranes or onset of labor.
There were no adverse events or maternal morbidity in either group.
For many patients, preinduction cervical ripening is becoming more common. We have previously shown that the Foley catheter is an effective form of preinduction cervical ripening in the inpatient setting.18,20 Preinduction cervical ripening in the outpatient setting may result in a significant decrease in hospital charges.9 With the apparent safety of the transcervical Foley catheter, moving preinduction cervical ripening using this method to the outpatient setting seemed a logical progression. In this trial, we demonstrated that the Foley catheter has similar efficacy and safety when used in the outpatient setting.
Previous trials performed outpatient cervical ripening using various methods. The most commonly used form of outpatient preinduction cervical ripening is PGE2 preparations. All but one of these trials has used a hospital-prepared PGE2 gel from ground or shaved PGE2 suppositories.10–15 These reports have used varying dosages by both the intravaginal and intracervical routes. Combined with the often liberal Bishop score required for entry,11–13 observational study design,15 inhospital management of some of the patients assigned to outpatient ripening,10 and small number of patients with a questionably significant power, the results of these trials are difficult to interpret.13 Furthermore, hospital-prepared extemporaneous gels have been criticized for the lack of standardized preparation and dosages.22 In our trial, we used a standardized protocol, which was based upon our two previous trials and our vast clinical experience with the Foley. Also, the Bishop score for entry clearly placed these patients at a low risk for spontaneous labor and vaginal delivery.
One of the key clinical questions for outpatient ripening has been the return rate to the hospital after the initiation of outpatient cervical ripening. Due to the experimental design of most of the previous trials, the rate of return to the hospital during outpatient cervical ripening had not been reported. However, two trials have reported return rates of 10%15 and 25%10 using a PGE2 preparation. Because of the nature of cervical ripening by the Foley catheter, we expected that there would be a higher rate of return to the hospital. Reassuringly, we found a similar return rate of 8%. This was most likely the result of careful counseling and reassurance that took place before and after randomization, as well as the comprehensive instruction form given to the outpatient group. We highly recommend using a similar approach when using outpatient cervical ripening, regardless of the method.
One of the considerations for both the patient and practitioner is the time involved in the induction process. The outpatient group spent a significantly longer time in preinduction cervical ripening. This was to be expected based on our experimental design. Women were asked to stay home even after the Foley was spontaneously expulsed. We designed the outpatient portion of the trial in this fashion with the intention that vaginal deliveries would occur at an earlier time in the day. In fact, 90.5% of women in the outpatient group and 86% of the inpatient group who delivered vaginally did so before midnight.
The lower cesarean delivery rate in the outpatient group is of interest, despite the lack of statistical significance. The reason for this is unclear, but may be attributed to the perception of a longer induction process in the inpatient group.23
One of the concerns with preinduction cervical ripening with hormonal methods is uterine tachysystole and hyperstimulation. In the literature, the rate has been reported as high as 3.3% using standardized PGE2 preparations24 and 1.6–3.6% with extemporaneous gels.25 Two previous outpatient trials have reported hyperstimulation rates. O'Brien et al,14 using an intravaginally applied extemporaneous PGE2 gel, reported a rate of 2%; and Farmer et al,9 using Prepidil (Pharmacia & Upjohn, Kalamazoo, MI), reported a rate of 1.3%. One patient in the latter trial required intravenous terbutaline to correct the hyperstimulation. Neither of these rates was significantly higher than would be expected, but bring attention to the necessity for detailed patient consent and careful fetal and maternal monitoring before the consideration of outpatient cervical ripening with a PGE2 preparation. We had no uterine contraction abnormalities during preinduction cervical ripening in either the inpatient or outpatient groups.
Controlled-release PGE2 inserts have recently become available in the United States. These inserts have the potential advantage of a slow constant release of PGE2. The uterine hyperstimulation rates appear similar to PGE2 gel. A study by Rayburn26 recently examined the use of Cervidil (Forrest Pharmaceuticals Inc., New York, NY) PGE2 vaginal insert for outpatient cervical ripening. Due to a high premature removal rate for regular contractions (24.3%) and hyperstimulation (4.5%), the authors came to the conclusion that Cervidil should be limited to inpatient therapy only.
There have been anecdotal reports of documenting the use of misoprostol in the outpatient setting. Recently, a preliminary report described the potential dangers of using misoprostol in this manner. After entering only 30 patients in a trial examining the possible use of misoprostol in the outpatient setting, there was a fetal death in the 200 μg oral misoprostol arm of the trial.27 Although it is hard to make meaningful conclusions based on this small sample size, this report certainly demonstrates the need for caution when considering the use of misoprostol in the outpatient setting, until a larger trial can address safety issues.
Safety must always be a concern when performing outpatient cervical ripening. One of the unique properties of the Foley catheter for cervical ripening is its apparent safety. Although its use has been associated with rupture of the membranes, chorioamnionitis, and endomyometritis,28 these instances appear to be highest with the addition of extra-amniotic saline infusion. In this trial, there were no cases of endomyometritis or chorioamnionitis in either group. Furthermore, inclusive of this time, 246 total patients have received Foley catheters in our most recent report. There has been only one case of endomyometritis and no cases of chorioamnionitis. Rupture of the membranes after placement has been noted, but very infrequently.
We have been using the Foley catheter almost exclusively for preinduction cervical ripening for the last 5 years and have had few complications. The only notable adverse event with the use of the Foley catheter was in a patient (not enrolled in a trial) with a previously undiagnosed low-lying placenta in which insufflation of the balloon caused a marginal separation of the placenta and resultant vaginal bleeding. For this reason, we recommend that patients who have not had a previous sonogram documenting the placement of the placenta have one before the Foley catheter placement.
Despite the randomized prospective nature of this trial, there are some limitations: 1) we did not control or have consistent guidelines for oxytocin use and the performance of cesarean delivery; 2) it was impossible to blind the practitioner to which group the patient was randomized; and 3) safety of outpatient cervical ripening was not the focus of the trial. Unfortunately, based on the uncommon occurrence of untoward outcomes in both groups, the ability to find a significant difference in poor outcomes between the groups would require a significant number of patients.
In conclusion, the Foley catheter appears to be a viable alternative for outpatient cervical ripening. Although our extensive experience with the Foley catheter for preinduction cervical ripening has shown that it is a safe and effective method, further experience will be needed to substantiate our findings in the outpatient setting. Until that information is available, we recommend that strict guidelines be developed for patient inclusion and clinical management. These guidelines should include some method or methods of fetal assessment before considering outpatient cervical ripening. Finally, all patients should be counseled about the risks and benefits before the initiation of outpatient cervical ripening.
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