Use of intravenous (IV) oxytocin is extremely common in modern obstetrics. Approximately 25% of all parturients require oxytocin for either induction or augmentation of labor.1 Despite its common use, no unanimity exists as to the optimal dosage regimen. Currently recommended starting doses range from 0.5 to 6 mU/minute.2–4 Dosage increments range from 1 to 6 mU/minute, and the interval between dosage increases ranges from 15 to 60 minutes.2–4
These wide ranges reflect discrepant results from various studies. Some studies suggest that the higher oxytocin dosages are associated with less need for cesarean delivery,5–7 others suggest an equivalent need for cesarean delivery,8–16 and a remaining study suggested less need in “augmentation cases” for cesarean birth for dystocia, but more need in “induction cases” for cesarean birth for fetal distress.17 Furthermore, higher-dose regimens in some studies were associated with shorter labors5,6,17–19; in others, labors did not differ significantly in length8,9,16,20; and in at least one widely quoted, nonrandomized study, labors were longer.21 The latter finding presumably occurred because oxytocin infusion is stopped or decreased more often for uterine hyperstimulation or fetal distress when higher dosages are being infused. Other investigators concur that higher doses are associated with a greater tendency toward hyper-stimulation, but that this hyperstimulation has no clinically significant effect.10
Considerable interest continues in understanding and determining the optimal dosages of oxytocin to improve obstetric outcomes. Clearly, important end points for studies of oxytocin administration include time spent in labor and need for cesarean delivery. Because these end points depend to a certain extent on the judgments of those caring for the patients involved, it is notable that no previous studies have masked the care practitioners to the oxytocin dosages being administered. Because of the strong possibility of observer bias complicating all previous reports, we designed and conducted large, double-masked, randomized trials of oxytocin use for the induction and augmentation of labor.
Materials and Methods
Any patient beyond 24 weeks' gestation with a living fetus who was scheduled to receive oxytocin for the induction or augmentation of labor in the labor and delivery unit of the University of Iowa Hospitals and Clinics was eligible for participation in this study, which had been approved by the institution's human subjects review committee. The patients who agreed to participate were divided into two groups: those who were prescribed oxytocin for augmentation of labor and those who were to receive oxytocin for induction of labor. For the purpose of the study (and randomization), we used the following definitions based on cervical dilatation and uterine contractions. All patients with cervical dilatation less than 3 cm were included in the induction group. Those with cervical dilatation of 3 cm or greater were assigned to the augmentation or induction group based on the number of uterine contractions noted before randomization (augmentation: at least ten contractions per hour; induction: fewer than ten contractions per hour). Those patients who were induced initially with a cervical ripening agent (ie, prostaglandin gel) were randomized also by the above schema as judged by the cervical dilatation and uterine contractions at the time at which they were to receive oxytocin (after receiving the ripening agent). The purpose of these definitions of induction and augmentation was to make it straightforward for the obstetric personnel on labor and delivery to correctly assign subjects to the induction or augmentation trials. Our concern was that the women with minimal cervical dilatation and some uterine contractions would, in the absence of such definitions, be assigned by some to the induction group and by others to the augmentation group.
Participants were given one of two oxytocin dosing regimens (described later). Assignment to high dose or low dose was determined by means of random-number tables located in the central pharmacy. After assignment by the staff to either the augmentation or induction group based on clinical criteria, this information was communicated to the pharmacy by means of a prescription. Separate random-number tables for the augmentation and induction groups were maintained in the central pharmacy, which assigned patients to the high or low dose.
To ensure double-masking of the oxytocin dose, all solutions were then prepared in the pharmacy according to the random assignment. For low dose, 5 U of oxytocin/500 mL 5% dextrose, ½ normal saline, was prepared, compared with 15 U of oxytocin/500 mL 5% dextrose, ½ normal saline, for the high-dose group. The IV solution was sent to the labor and delivery unit for administration. The bags containing the high-dose and low-dose solutions were identical except for an indistinguishable volume difference (500.5 mL compared with 501.5 mL). Low-dose infusion was begun at 1.5 mU/minute (9 mL/hour) and increased by 1.5 mU/minute every 30 minutes until adequate labor was established. High-dose infusion was begun at 4.5 mU/minute (9 mL/hour) and increased by 4.5 mU/minute every 30 minutes. Thus, infusion volumes were identical in both groups. If infusion volumes were deemed excessive, the solutions were “double concentrated” again using the same formula as above. No maximum dosage of oxytocin was specified.
Oxytocin was decreased or discontinued for hyper-stimulation in the absence of fetal heart rate (FHR) abnormalities only if there were more than seven contractions in a 15-minute period. If severe FHR abnormalities occurred, the oxytocin infusion was discontinued. For milder abnormalities, discretion was left to those attending the patient as to whether the oxytocin should be discontinued or whether the rate of infusion should be slowed.
If oxytocin was given for 8–12 hours without any progress in the induction process, the clinical staff could elect to discontinue the oxytocin solution and either reapply a cervical ripening agent or reinitiate oxytocin the next day. For the purposes of this study, these patients were described as having “failed inductions.” These patients were then given oxytocin in an unmasked fashion. Route of delivery, labor data, and neonatal outcomes were not included for this group.
All outcome data for this study were tabulated and entered into a computer database before breaking the code and revealing the dosages of oxytocin received. All values are expressed as mean ± standard error of the mean or percent. Groups were compared by one-way analysis of variance, χ2, or Fisher exact test (for small cells). All analyses were conducted on an intent-to-treat basis. P < .05 was considered statistically significant. Power calculations were performed before initiation of the study to determine the necessary sample size. Power calculations were conducted by using the necessary sample size to detect a shortening of labor by 1 hour in the induction group and by 45 minutes in the augmentation group. Based on previously published5,9–11 standard deviations, α = .05, and β = .20, we determined that 393 patients in each arm (high dose, low dose) were necessary in the induction group and 175 patients were necessary in each arm of the augmentation group (two-tailed test).
A participation profile diagram of the randomized trials is depicted in Figure 1. Between March 1994 and March 1997, a total of 816 patients (low dose 412; high dose 404) were randomized in the induction portion and 491 patients (low dose 242; high dose 249) were randomized in the augmentation portion. Only a single enrolled patient was excluded from the final analysis. This patient was enrolled in the induction group and was randomized to receive the high dose. An initial decision was made to proceed with induction in this patient, who was diagnosed with mild preeclampsia. However, after this patient received oxytocin (on the study) for approximately 10 minutes, a second faculty member reversed the decision, and the induction was discontinued. A total of 36 patients were randomized but did not receive oxytocin because they progressed spontaneously (induction: 17 of 815, 2.1%; augmentation: 19 of 491, 3.9%). These patients were included in the analysis, however (intent to treat). During the study period (March 1994 to March 1997), a total of 363 patients received oxytocin outside of the study; thus, 1307 of 1670 (78.3%) of the patients receiving oxytocin at the University of Iowa Hospitals and Clinics were enrolled in the study.
Results of the induction portion of the study are presented in Tables 1–4. There were no significant differences in the maternal age or gestational age between the low-dose and high-dose groups. In addition, similar numbers of patients were nulliparous (approximately 50%) in both groups. Despite randomization, there were more multiple gestations noted in the low-dose compared with the high-dose group (3.4% and 0.2%). All were twins. Maternal race was also not significantly different between the groups, with the vast majority (approximately 80%) in each group being white. The most common indications for induction in both groups were premature rupture of membranes (PROM) without labor, preeclampsia, and fetal complications. Overall, there were no significant differences in the indications for induction between the groups.
Mean cervical dilatation at the initiation of oxytocin was identical in both groups (Table 2). The percentage of patients with a Bishop score of less than 4 at the time of initiation of oxytocin was also not significantly different between groups. The other factors of interest in Table 2 were likewise similar.
With high-dose oxytocin, we observed a significant shortening of labor as determined by both the time from initiation of oxytocin to complete dilatation and the time from initiation of oxytocin to delivery (Table 3). For both, high-dose oxytocin significantly shortened labor by approximately 2 hours. The mean maximum dose of oxytocin used was significantly higher in the high-dose group (high dose: 29.5 ± 0.9 mU/minute; low dose: 14.9 ± 0.4 mU/minute). Oxytocin dosages in the low-dose group ranged from 1.5 to 48 mU/minute, compared with 4.5–117 mU/minute in the high-dose group. The total cesarean delivery rate for the low-dose group was 15.0%, compared with 11.3% in the high-dose group (P = .17). It is interesting that cesareans for both cephalopelvic disproportion and fetal distress tended to be lower in the high-dose group. Approximately 6% of the patients in each group had failed inductions (as defined in the Materials and Methods section).
We observed that oxytocin was decreased or discontinued more commonly in the high-dose group both for uterine hyperstimulation and for FHR abnormalities. The mean total number of times that oxytocin was decreased or discontinued in the high-dose group was 1.6, compared with 1.2 in the low-dose group (P = .002). Presenting the data in a different manner, we found that the percentage of patients in the low-dose group who did not have the oxytocin decreased or discontinued at all was 43%, compared with 35% in the high-dose group (P = .02). In contrast, 30% of the patients in the low-dose group had the oxytocin decreased or discontinued two or more times, compared with 41% in the high-dose group (P = .002).
We observed no significant differences in the incidence of placental abruption, chorioamnionitis, postpartum hemorrhage, or endometritis between the low-dose and high-dose groups. In addition, the number of maternal hospital days was not significantly different between the groups. We observed one uterine rupture in each group. Both occurred in women having vaginal birth after cesarean (VBAC) who had previously undergone two low transverse cesarean deliveries.
Neonatal outcomes are shown in Table 4. We observed no significant difference in birth weight between the low-dose and high-dose groups. In addition, various measures of fetal distress such as a 5-minute Apgar score less than 7, umbilical vein pH less than 7.20, or umbilical artery pH less than 7.10 were not significantly different between the groups. The mean number of neonatal hospital days and the incidence of neonatal death were also not significantly different. All neonatal deaths were secondary to severe anomalies (n = 7), karyotypic abnormalities (n = 1), or severe prematurity (n = 1).
A total of 423 nulliparous women were randomized in the induction portion of the study (low dose 216; high dose 207). In nulliparous women, high-dose oxytocin was associated with a significant shortening of labor by approximately 2 hours (oxytocin to complete dilatation: 10.6 ± 0.4 hours compared with 8.7 ± 0.3 hours, P < .001; oxytocin to delivery: 11.7 ± 0.5 hours compared with 9.9 ± 0.4 hours, P = .002). The cesarean delivery rate also tended to be lower, but not significantly, in nulliparous women receiving high-dose oxytocin (17.3% compared with 11.7%, P = .15), especially the rate for cephalopelvic disproportion or failure to progress (11.9% compared with 5.9%, P = .06). In nulliparas, cesareans for fetal distress were equally common in the two groups (low dose 5.0%, high dose 5.3%; P = .95).
When only women with unscarred uteri were included in the analysis (low dose: n = 362; high dose: n = 358), high-dose oxytocin was again associated with significantly shorter labors (oxytocin to complete dilatation: 9.6 ± 0.3 compared with 7.7 ± 0.3 hours, P < .001; oxytocin to delivery: 10.4 ± 0.3 compared with 8.5 ± 0.3 hours, P < .001). Total cesarean rates also tended to be lower with high-dose oxytocin (13.1% compared with 9.9%, P = .23), especially those performed for cephalopelvic disproportion or failure to progress (8.4% compared with 4.8%, P = .08).
Results from the augmentation portion of the study are presented in Tables 5–7. Important maternal demographic variables are listed in Table 5. There were no significant differences in maternal age, gestational age, percentage of nulliparous women, percentage of epidural use, percentage with PROM, or percentage of VBACs between the groups. Only a small percentage of patients in each group had intact membranes at the time oxytocin was initiated (low dose 4.0%, high dose 6.1%; P = .39). Despite randomization, significantly more patients receiving high-dose oxytocin had originally been induced (low dose 21.5%, high dose 32.5%; P = .008). These patients underwent labor induction either by amniotomy or with cervical ripening agents. In addition, significantly more patients receiving high-dose oxytocin had previously received cervical ripening (low dose 7.9%, high dose 16.9%; P = .004).
When used for augmentation, high-dose oxytocin was associated with a significant shortening of labor as demonstrated by the time from initiation of oxytocin to delivery (low dose: 5.1 ± 0.2 hours; high dose: 4.4 ± 0.2 hours; P = .03) (Table 6). This shortening of labor occurred even though oxytocin was decreased or stopped more frequently when given in the high dose. It should be noted, however, that more than 50% of the patients in each group did not need to have the oxytocin infusion decreased or discontinued during augmentation. No significant differences were noted in the need for cesarean delivery (for cephalopelvic disproportion, failure to progress, or fetal distress) between the groups. In addition, there were no significant differences in the various neonatal outcome variables (Table 7). There were four neonatal deaths in the augmentation arm of the study. These occurred in the high-dose group and all four were secondary to severe fetal or karyotypic abnormalities.
Because of the differences in the percentages of patients who had undergone labor induction, we examined the subgroup of patients (n = 358; low dose 190, high dose 168) who had proceeded into labor spontaneously and subsequently received oxytocin for augmentation of dysfunctional labor.
In this subgroup, high-dose oxytocin was again associated with a significant shortening of labor as demonstrated by the interval from initiation of oxytocin to delivery (low dose: 5.0 ± 0.2 hours; high dose: 4.3 ± 0.2 hours; P = .04). Neither the total cesarean rate (low dose 9.5%, high dose 8.9%) nor the cesarean rate for various indications differed significantly between the groups (cephalopelvic disproportion or failure to progress: low dose 8.4%, high dose 7.7%; distress: low dose 0.5%, high dose 0.6%). There were no differences between the groups in maternal age, percentage of nulliparas, maternal race, epidural use, or percentage of women undergoing VBAC. In addition, only a small number of patients in each group had intact membranes at the time oxytocin was initiated (low dose 2.8%; high dose 4.2%). Interestingly, mean cervical dilatation at the time of initiation of oxytocin was significantly greater in the low-dose group (low dose 5.2 ± 0.1 cm compared with high dose 4.8 ± 0.1 cm; P = .01). No differences were noted in any of the neonatal outcome variables between the groups.
As part of this study, we also conducted a cost analysis for the use of low-dose compared with high-dose oxytocin. At the University of Iowa Hospitals and Clinics, there is an hourly charge for IV oxytocin administration with standard maternal and fetal monitoring ($140.00). The charge for oxytocin currently is $13.40 per ampule (10 U/mL). For the low-dose protocol, 5 U of oxytocin per 500 mL was used, compared with 15 U/500 mL for the high-dose solution (one or two ampules). Therefore, the total extra charge for oxytocin in the high-dose group averages $13.40. For the induction portion of this study, labor was shortened by approximately 2 hours with high-dose oxytocin. The average extra labor and delivery charge for the low-dose group thus approximates $260.00/patient [($140.00 × 2) − $13.40 = $266.10]. Therefore, if all 815 patients in the induction portion of the study had received high-dose oxytocin (compared with low dose), a total of $211,900.00 would have been saved without any demonstrable change in neonatal outcomes. A similar calculation for the augmentation arm (assuming shortening of labor by approximately 1 hour) results in savings of approximately $62,160.60. Thus, we estimate that over the 3-year study period, a total reduction of $274,060.00 in labor and delivery charges would have occurred through the use of high-dose oxytocin. These savings would have occurred secondary to shortening of labor and do not include any estimates of cost reduction secondary to a trend in decreased cesarean delivery rates with high-dose oxytocin in the induction group.
It is estimated that approximately 10% of all patients in the United States require oxytocin for induction of labor and 15% for augmentation. In 1996, more than 3.9 million births occurred in the United States,22 and thus we estimate that 390,000 inductions and 585,000 augmentations of labor occurred. If the results from the present study could be extrapolated to the United States as a whole, high-dose oxytocin use could result in substantial savings (more than $170,000,000 per year) of health care dollars (390,000 × $260.00/patient + 585,000 × $125.00 = $174,525,000.00/year).
Even though synthetic oxytocin is one of the most commonly used drugs in modern obstetric practice, considerable controversy exists concerning its administration. It is estimated that in most obstetric units, 15–25% of women require oxytocin for either augmentation or induction of labor.1 If misused, oxytocin can lead to important complications, such as uterine hyper-stimulation, fetal distress, uterine rupture, and, rarely, water intoxication. The goal in using oxytocin for the augmentation or induction of labor clearly is to increase the likelihood of vaginal delivery while not harming either mother or fetus. All previous studies concerning oxytocin use have suffered from a lack of masking and thus the strong potential for observer bias. In the present study, in which oxytocin was administered in a double-masked fashion, we observed that a higher dosage regimen was associated with significantly shorter labors and a statistically nonsignificant tendency for fewer cesarean deliveries, without any demonstrable adverse fetal or neonatal effects.
To lend historic perspective to the oxytocin controversy, it is important to point out that before 1980, most institutions used protocols that would be considered aggressive by today's standards. The work of Seitchik et al21,23–25 between 1982 and 1984 raised many questions concerning the use of oxytocin and subsequently led many institutions to change their oxytocin protocols. Before Seitchik's work, oxytocin protocols commonly began at 1 mU/minute and increased by 1–2 mU/minute every 15 to 20 minutes or, in some protocols, the dose was doubled every 15 to 20 minutes. Seitchik et al21 examined the outcomes of a small group of patients receiving oxytocin by various protocols for augmentation of labor. One group was given oxytocin by a computer-driven system whereby the dose was increased by 1.0 mU/minute at not less than 30-minute intervals, whereas a second group was managed by the obstetric residents and was given oxytocin per the discretion of the house officers. The authors found that the computer-managed patients had oxytocin stopped or the dosage reduced less often, had shorter intervals from the initiation of oxytocin to full dilatation, and required smaller maximum doses of oxytocin. In a separate study,23 they examined the pharmacokinetics of oxytocin and found that plasma oxytocin levels increased linearly with each dose for the first 40 minutes of the infusion. On the basis of these data, many institutions adopted oxytocin protocols that began at 1 mU/minute and increased by 1 mU/minute at 30–40-minute intervals. Furthermore, although the studies of Seitchik et al21,23–25 involved only labor augmentation, many institutions adopted similar low-dose protocols for both labor induction and augmentation.
In contrast to this less aggressive approach to oxytocin administration is the protocol used at the National Maternity Hospital in Dublin, Ireland, as part of its active management of labor.26,27 Clearly, the active management of labor involves more than just a higher dosage of oxytocin; however, their success in achieving vaginal delivery (cesarean delivery rates of 5–6%) is compelling. In this protocol, oxytocin is initiated at 6.0 mU/minute and is increased by 6.0 mU/minute at 15-minute intervals.
Because of the success of the protocol used in Ireland, considerable interest exists in determining the optimal protocol for oxytocin administration. Since 1990, a total of 12 randomized trials comparing low-dose with high-dose oxytocin have been conducted.6,8–16,20,28 All but two of the trials6,15 used oxytocin for the induction of labor only. In these studies, a variety of different oxytocin protocols were used, making comparisons difficult. Seven of the studies compared different dosing intervals,8,9,12–14,20,28 one compared different dosages with identical intervals,16 and four compared protocols in which both the dosage interval and dosage increases were different.6,10,11,15 Furthermore, all but two of these studies were relatively small, with fewer than 250 patients total. In the two largest studies,6,15 mixed results were obtained. Lazor et al15 found that high-dose oxytocin was not associated with any change in the cesarean delivery rate or in the overall length of labor. In contrast, Xenakis et al6 found that the use of high-dose oxytocin for labor augmentation was associated with a significant decrease in the cesarean delivery rate (25.7% to 10.4%) and in the time needed to correct the labor abnormality. Further controversy stems from the findings of a large, prospective, nonrandomized study of low-dose compared with high-dose oxytocin for both augmentation and induction of labor.17 In this study, a low-dose protocol was used first for 5 months in 1251 pregnancies, and the high-dose protocol was used in 1537 pregnancies during the subsequent 5-month period. In augmented labor, high-dose oxytocin was associated with fewer cesarean deliveries for dystocia and no difference in cesareans for fetal distress. However, with induced labor, high doses of oxytocin were associated with an increase in cesareans for fetal distress.
Three separate studies5,18,19 in the United States have addressed the efficacy and safety of an active management of labor program, as proposed by the Dublin group.26,27 In all three studies (none of which were masked), active management of labor that included high-dose oxytocin regimens was associated with significant shortening of labor. Only one of the three studies5 demonstrated a statistically significant decrease in cesarean deliveries in the active management of labor group.
Many of the previous studies indicated an increased incidence or tendency for uterine hyperstimulation with higher doses of oxytocin. In the study by Seitchik et al,21 an increased incidence of hyperstimulation with subsequent discontinuation of the infusion was offered as the explanation for the increased duration of labor with high-dose oxytocin. The results of the present study are particularly interesting in this regard. We observed that when oxytocin was given in higher dosages in a masked fashion, the infusion was decreased or discontinued more often for hyperstimulation, but this had no clinical consequences. In fact, even though the infusion was decreased or discontinued more often, the labor was significantly shorter, not longer.
In this study, we did not observe any differences in neonatal outcomes with high-dose oxytocin when used for either augmentation or induction of labor. Specifically, we did not observe any differences in any of the following: Apgar scores (less than 7 at 5 minutes), percentage with acidosis at birth, length of neonatal hospital stay, or neonatal mortality. All neonatal deaths in this study were secondary to severe fetal anomalies, karyotypic abnormalities, or extreme prematurity. It should be pointed out, however, that neonatal death was an infrequent outcome in this study and an even larger population would be needed to study this outcome variable.
We observed three cases of uterine rupture (all in patients attempting VBAC), with two of these occurring in the low-dose group and one in the high-dose group. In two of the three cases, the patients had undergone two previous cesareans. In none of the three cases was uterine rupture preceded by uterine hyperstimulation. Similar findings were noted in a recent case-control study,29 in which patients with uterine rupture were noted to have fewer hyperstimulation episodes than a group of women who had a successful VBAC. In previous retrospective studies,30–32 the use of oxytocin in patients laboring after previous cesarean was not found to predispose to uterine rupture. However, a case-control study of uterine ruptures implicated both excessive oxytocin, not otherwise defined, and the presence of two previous cesareans.33 Although the total number of VBAC patients who received high-dose oxytocin in the study was relatively small (71 total), we found no increased incidence of uterine rupture in this group compared with those who received low-dose oxytocin.
In addition to studies comparing high-dose and low-dose oxytocin, several reports have been published on the use of pulsatile oxytocin administration for labor induction or augmentation.34–37 In these studies, intermittent, pulsatile oxytocin administration was compared with continuous IV administration at relatively low dosages. No significant differences were found between the groups in these studies except for decreased mean dosages of oxytocin in the pulsatile group.
One could argue that the results of the present study may not be applicable to other patient populations. In this regard, two maternal demographic characteristics appear to be significant and deserve comment. In this study, the majority of patients received epidural anesthesia (approximately 70%) and the majority were white (approximately 80%). Satin et al38 examined factors that could affect the dose response to oxytocin and found that use of epidural anesthesia and maternal race were not important variables. In their study, the statistically significant predictors of the maximum dosage of oxytocin required included only cervical dilatation, parity, and gestational age. It is also important to note that Chestnut et al39 reported that early administration of epidural anesthesia did not prolong labor or alter the cesarean rate in nulliparous women who were receiving IV oxytocin.
1. Owen J, Hauth JC. Oxytocin for the induction or augmentation of labor. Clin Obstet Gynecol 1992;35:464–75.
2. ACOG technical bulletin. Dystocia and augmentation of labor. Number 218-December 1995. Int J Gynaecol Obstet 1996;53:73–80.
3. American College of Obstetricians and Gynecologists. Induction of labor. ACOG technical bulletin no. 217. Washington DC: American College of Obstetricians and Gynecologists, 1995.
4. American College of Obstetricians and Gynecologists. Dystocia and the augmentation of labor. ACOG technical bulletin no. 218. Washington DC: American College of Obstetricians and Gynecologists, 1995.
5. Lopez-Zeno JA, Peaceman AM, Adashek JA, Socol ML. A controlled trial of a program for the active management of labor. N Engl J Med 1992;326:450–4.
6. Xenakis EMJ, Langer O, Piper JM, Conway D, Berkus MD. Low-dose versus high-dose oxytocin augmentation of labor—a randomized trial. Am J Obstet Gynecol 1995;173:1874–8.
7. Satin AJ, Leveno KJ, Sherman ML, Mclntire D. High-dose oxytocin: 20- versus 40-minute dosage interval. Obstet Gynecol 1994;83:234–8.
8. Blakemore KJ, Qin N-G, Petrie RH, Paine LL. A prospective comparison of hourly and quarter-hourly oxytocin dose increase intervals for the induction of labor at term. Obstet Gynecol 1990;75:757–61.
9. Chua S, Arulkumaran S, Kurup A, Tay D, Ratnam SS. Oxytocin titration for induction of labour: A prospective randomized study of 15 versus 30 minute dose increment schedules. Aust N Z J Obstet Gynaecol 1991;32:134–7.
10. Satin AJ, Hankins GDV, Yeomans ER. A prospective study of two dosing regimens of oxytocin for the induction of labor in patients with unfavorable cervices. Am J Obstet Gynecol 1991;165:980–4.
11. Mueller PR, Stubbs TM, Laurent SL. A prospective randomized clinical trial comparing two oxytocin induction protocols. Am J Obstet Gynecol 1992;167:373–81.
12. Orhue AAE. Incremental increases in oxytocin infusion regimens for induction of labor at term in primigravidas: A randomized controlled trial. Obstet Gynecol 1994;83:229–31.
13. Orhue AAE. A randomized trial of 30-min and 15-min oxytocin infusion regimen for induction of labor at term in women of low parity. Int J Gynaecol Obstet 1995;40:215–25.
14. Orhue AAE. A randomised trial of 45 minutes and 15 minutes incremental oxytocin infusion regimens for the induction of labour in women of high parity. Br J Obstet Gynaecol 1993;100:126–9.
15. Lazor LZ, Phillipson EH, Ingardia CJ, Kobetitsch ES, Curry SL. A randomized comparison of 15- and 40-minute dosing protocols for labor augmentation and induction. Obstet Gynecol 1993;82:1009–12.
16. Hourvitz A, Alcalay M, Korach J, Lusky A, Barkai G, Seidman DS. A prospective study of high- versus low-dose oxytocin for induction of labor. Acta Obstet Gynecol Scand 1996;75:636–41.
17. Satin A], Leveno KJ, Sherman ML, Brewster DS, Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet Gynecol 1992;80:111–6.
18. Rogers R, Gilson GJ, Miller AC, Izquierdo LE, Curet LB, Quails CR. Active management of labor: Does it make a difference? Am J Obstet Gynecol 1997;177:599–605.
19. Frigoletto FD Jr, Lieberman E, Lang JM, Cohen A, Barss V, Ringer S, et al. A clinical trial of active management of labor. N Engl J Med 1995;333:745–50.
20. Mercer B, Pilgrim P, Sibai B. Labor induction with continuous low-dose oxytocin infusion: A randomized trial. Obstet Gynecol 1991;77:659–63.
21. Seitchik J, Castillo M. Oxytocin augmentation of dysfunctional labor. I. Clinical data. Am J Obstet Gynecol 1982;144:899–905.
22. Ventura SJ, Peters KD, Martin JA, Maurer JD. Births and deaths: United States, 1996. Monthly vital statistics report vol 46 (suppl 2):1–44. Hyattsville, Maryland: National Center for Health Statistics, 1997.
23. Seitchik J, Amico J, Robinson AG, Castillo M. Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol 1984;150:225–8.
24. Seitchik J, Castillo M. Oxytocin augmentation of dysfunctional labor. III. Multiparous patients. Am J Obstet Gynecol 1982;145:777–80.
25. Seitchik J, Castillo M. Oxytocin augmentation of dysfunctional labor. II. Uterine activity data. Am J Obstet Gynecol 1983;145:526–9.
26. O'Driscoll K, Foley M, MacDonald D. Active management of labor as an alternative to cesarean section for dystocia. Obstet Gynecol 1984;63:485–90.
27. O'Driscoll K, Jackson RJA, Gallagher JT. Active management of labour and cephalopelvic disproportion. J Obstet Gynaecol Br Commonw 1970;77:385–9.
28. Goni S, Sawhney H, Gopalan S. Oxytocin induction of labor: A comparison of 20- and 60-min dose increment levels. Int J Gynaecol Obstet 1995,48:31–6.
29. Phelan JP, Korst LM, Settles DK. Uterine activity patterns in uterine rupture: A case-control study. Obstet Gynecol 1998;92:394–7.
30. Rosen MG, Dickinson JC, Westhoff CL. Vaginal birth after cesarean: A meta-analysis of morbidity and mortality. Obstet Gynecol 1991;77:465–70.
31. Horenstein JM, Phelan JP. Previous cesarean section: The risks and benefits of oxytocin usage in a trial of labor. Am J Obstet Gynecol 1985;151:564–9.
32. Phelan JP, Ahn MO, Diaz F, Brar HS, Rodriguez MH. Twice a cesarean, always a cesarean? Obstet Gynecol 1989;73:161–5.
33. Leung AS, Farmer RM, Leung EK, Medearis AL, Paul RH. Risk factors associated with uterine rupture during trial of labor after cesarean delivery: A case-control study. Am J Obstet Gynecol 1993;168:1358–63.
34. Cummiskey KC, Gall SA, Dawood MY. Pulsatile administration of oxytocin for augmentation of labor. Obstet Gynecol 1989;74:869–72.
35. Cummiskey KC, Dawood MY. Induction of labor with pulsatile oxytocin. Am J Obstet Gynecol 1990;163:1868–74.
36. Willcourt RJ, Pager D, Wendel J, Hale RW. Induction of labor with pulsatile oxytocin by a computer-controlled pump. Am J Obstet Gynecol 1994;170:603–8.
37. Reid GJ, Helewa ME. A trial of pulsatile versus continuous oxytocin administration for the induction of labor. J Perinatal 1995;15:364–6.
38. Satin AJ, Leveno KJ, Sherman L, Mclntire DD. Factors affecting the dose response to oxytocin for labor stimulation. Am J Obstet Gynecol 1992;166:1260–1.
39. Chestnut DH, Vincent RD Jr, McGrath JM, Choi WW, Bates JN. Does early administration of epidural analgesia affect obstetric outcome in nulliparous women who are receiving intravenous oxytocin? Anesthesiology 1994;80:1193–200.