Obstetrics & Gynecology 2001;97:381-384
© 2001 by The American College of Obstetricians and Gynecologists
Oxytocin Dose and the Risk of Uterine Rupture in Trial of Labor After Cesarean
LAURA GOETZL, MD, MPH,
THOMAS D. SHIPP, MD,
AMY COHEN,
CAROLYN M. ZELOP, MD,
JOHN T. REPKE, MD and
ELLICE LIEBERMAN, MD, DrPH
From the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; the Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts; the Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, Massachusetts; and the Departments of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, Nebraska.
Address reprint requests to: Laura Goetzl, MD, MPH, 1921 North Boulevard, Houston, TX 77098, E-mail: lgoetzl{at}hotmail.com
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Abstract
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Objective: To examine the association between uterine rupture and oxytocin use in trial of labor after cesarean.
Methods: A case-control study was performed. Cases were all women with uterine ruptures who received oxytocin during a trial of labor after a single cesarean delivery within a 12-year period (n = 24). Four controls undergoing trial of labor after a single cesarean delivery were matched to each case by 500 g birth weight category, year of birth, and by induction or augmentation (n = 96). The study had an 80% power to detect a 40% increase in oxytocin duration or a 65% increase in total oxytocin dose.
Results: No significant differences were seen in initial oxytocin dose, maximum dose, or time to maximum dose. Although women with uterine ruptures had higher exposure to oxytocin as measured by mean total oxytocin dose (544 mU higher) and oxytocin duration (54 minutes longer), these differences were not statistically significant. Women with uterine rupture who received oxytocin were more likely to have experienced an episode of uterine hyperstimulation (37.5% compared with 20.8%, P = .05). However, the positive predictive value of hyperstimulation for uterine rupture was only 2.8%.
Conclusion: Although no significant differences in exposure to oxytocin were detected between cases of uterine rupture and controls, the rarity of uterine rupture limited our power to detect small differences in exposure. In women receiving oxytocin, uterine rupture is associated with an increase in uterine hyperstimulation, but the clinical value of hyperstimulation for predicting uterine rupture is limited.
Efforts to reduce the cesarean delivery rate have led to an increased emphasis on encouraging a trial of labor in women with a prior cesarean delivery. Whereas the overall risk of uterine rupture is reported at 0.2–1.5% for women with a prior low transverse incision,1 the risk of uterine rupture appears to be higher in certain clinical situations. We recently reported an increased risk of uterine rupture associated with oxytocin induction after controlling for potential confounders.2 Oxytocin augmentation was associated with a somewhat higher rate of uterine rupture, but the difference was not statistically significant. Other studies have reported an increased risk associated with either high-dose oxytocin,3 or use of oxytocin in the latent phase.4,5
Given these findings, we performed the current analysis to examine whether differences in dose or pattern of oxytocin use influence the risk of uterine rupture during trial of labor. Studies of this nature may distinguish subgroups of women who are appropriate candidates for induction from others who may benefit from elective cesarean delivery. In addition, more information is needed to guide protocols for oxytocin administration in patients with a prior uterine scar.
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Materials and Methods
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The discharge diagnoses of all patients admitted to the labor and delivery floor at the Brigham and Women’s Hospital during a 12-year period (July 1984 to June 1996) were searched to identify women undergoing a trial of labor after a prior cesarean delivery. For the current study, eligible patients were selected from all full-term primiparas undergoing a trial of labor after one prior cesarean (n = 1650) with no other deliveries. The population included women with a low-transverse incision, a low-vertical incision, or an unknown incision type. Within this cohort, a nested matched case-control study was performed. For the current analysis, cases comprised the 24 women with uterine rupture who received oxytocin for induction or augmentation. Four controls were matched to each case by birth weight (within the same 500-g category), year of delivery, and by whether they were induced or augmented, resulting in 96 controls. For two cases, only two controls each were available within the same calendar year. For each of these cases, two additional controls were chosen from the adjoining calendar year; for all controls, the date of delivery was within 5 months of the reference case. When more than four controls were available, controls were randomly selected.
The pattern of oxytocin dosing in cases and controls was reviewed. In general, oxytocin increased in increments of 1 to 2 mU/minute every 15–30 minutes, to a maximum of 20 mU/minute, according to the individual care provider. Information was also collected on reported episodes of hypertonus and hyperstimulation. Hypertonus was defined as a physician diagnosis of hypertonus in the medical record that resulted in reduced administration of oxytocin. Hyperstimulation was defined as documented uterine contractions more frequent than every 2 minutes that resulted in reduced administration of oxytocin. Exposure to prostaglandin E2 gel was recorded. One case of uterine rupture was missing information regarding frequency of uterine contractions. Given the absence of a physician diagnosis of hyperstimulation or hypertonus the case was placed in the normal uterine activity group.
Only women with symptomatic uterine rupture were included as cases in our analysis. Symptomatic rupture was defined as a complete disruption of the prior uterine scar in association with at least one of the following symptoms or signs: laparotomy for hemorrhage or hemoperitoneum, excessive injury to the bladder or extrusion of any part of the fetus or placenta into the peritoneal cavity, cesarean delivery for nonreassuring fetal heart rate tracing, or acute onset of abdominal pain. Cases of asymptomatic dehiscence were excluded.
Statistical analyses used the PHREG procedure in the SAS System (SAS Institute, Cary, NC) to carry out conditional logistic regression analyses that took into account matched sets in evaluating case-control data. Analyses controlled for the potential confounding effect of maternal age. The 
2 or Fisher exact test was used to test the statistical significance for proportions and the t test was used for continuous variables. Results were considered statistically significant when P < .05. Power analyses were performed using the Power and Precision program (Dataxiom Software Inc., Los Angeles, CA). The study had an 80% power to detect a 40% increase in oxytocin duration or a 65% increase in total oxytocin dose.
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Results
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The matching process was successful in producing cases and controls that were similar with respect to their baseline characteristics (Table 1
) except for maternal age. On average, cases of uterine rupture were 2.5 years older than controls. Birth weight (3693 and 3676 g), rate of public insurance (12.5% and 18.5%), gestational age (39.3 and 39.4 weeks), and use of epidural analgesia (88% and 83%) were similar in cases and controls. Fifty-four percent of both cases and controls were induced, whereas the remainder were augmented. Women who later experienced uterine rupture during their trial of labor after cesarean delivery presented with similar cervical examinations, and labored exactly the same number of hours, on average, as women who did not experience uterine rupture. Most women had a prior low-transverse incision (83% in both groups) whereas the remainder had low-vertical or unknown prior incisions. We did not stratify our results by type of incision as the literature does not support a higher rate of rupture with low-vertical incision.6,7 In addition, we have demonstrated in our population that women with a prior low-vertical incision are not at increased risk for uterine rupture.8
The pattern of oxytocin use was similar for women who experienced uterine rupture during a trial of labor after cesarean delivery and women who did not (Table 2). Mean initial dose of oxytocin, interval to dose increase, maximum oxytocin dose, and time to maximum dose were similar in cases and controls. The mean duration at maximum dose of oxytocin was somewhat lower in rupture cases (122 minutes compared with 140 minutes) but not statistically different (P = .84). Women with ruptures had a somewhat higher mean total oxytocin dose (5235 compared with 4691 mU, P = .14) and mean duration of oxytocin use (530 minutes compared with 476 minutes, P = .08). Whereas the trend toward a higher duration of oxytocin use did not reach statistical significance, our study had only 14% power to detect a difference of this magnitude. We therefore examined the data to determine whether there might be a cutoff that was clinically useful for predicting rupture (Table 3). Because the proportion of women receiving more than 12 hours of oxytocin was similar in the case and control groups, it is unlikely that this would provide useful clinical guidance, even if there was a small difference in oxytocin duration. When patients were stratified by induction and augmentation, the same patterns for duration and total dose were present (Table 4), but again, none of the differences was statistically significant.
Because it has been suggested that receiving oxytocin for augmentation in the latent phase may be associated with an increased risk of rupture,4,5 we examined this issue in the subset of augmented women. Oxytocin was administered at greater than 4 cm in 14% of cases and 24% of controls (P = .3), suggesting that early administration did not increase the risk of rupture in our population.
Episodes of abnormal uterine activity were examined in the case and control groups (Table 5). A significantly higher rate of uterine hyperstimulation associated with uterine rupture was found in the overall group (37.5% rupture, 20.8% no rupture) and in the augmented group (36.4% rupture, 9.1% no rupture). There was also a slightly higher rate of hyperstimulation in cases of uterine rupture in the induced group as well (38.5% rupture, 30.8% no rupture), but the difference was not statistically significant. No association was observed between risk of uterine rupture and uterine hypertonus in the overall, induced, or augmented group.
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Discussion
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Prior studies have shown an association between induction, oxytocin use, and uterine rupture during trial of labor after cesarean delivery.2–5 One aim of our study was to determine if any clear, clinically useful differences in pattern of oxytocin use could be identified between women who experience uterine rupture and those who do not. Our study does not indicate that differences in the dose or patterns of use of oxytocin are substantial enough to use as the basis for safer induction protocols in women desiring trial of labor after prior cesarean delivery. Although not statistically significant, total oxytocin dose was 11.6% higher and oxytocin duration was 10.2% higher in women with uterine ruptures. However, duration at maximum dose was 12.9% lower in cases of uterine rupture. This lack of a consistent pattern suggests that these differences may be due to chance alone.
Given the rarity of uterine rupture, the power of this study was limited to detect differences of this magnitude. Our study had an 80% power to detect a 40% increase in oxytocin duration. However, even if total oxytocin dose or duration is 10% higher in cases of uterine rupture, the lack of clear cutoff levels limits the clinical usefulness of this information. Very large studies would be needed to determine if small increases in oxytocin exposure are associated with rupture.
Although the increased rate of uterine hyperstimulation during induction in cases of uterine rupture is intriguing, the positive predictive value of this finding in a clinical setting is limited. In this population, women exposed to oxytocin during labor had a 1.5% rate of uterine rupture,2 resulting in a positive predictive value for uterine hyperstimulation of only 2.8%. Thus, whereas women with uterine hyperstimulation can be considered at somewhat increased risk, most will not experience an adverse outcome. It was not possible to determine from these data whether oxytocin-associated hyperstimulation increased the risk of uterine rupture by weakening the uterine scar, or whether hyperstimulation is a symptom of uterine irritation in a uterus undergoing rupture. Although the risk of uterine rupture is low, women exposed to oxytocin who later develop uterine hyperstimulation should be followed vigilantly for signs of uterine rupture. Our study is reassuring in that very large differences in the use of oxytocin are not an important factor in predicting uterine rupture. Larger studies are needed to refine the management of oxytocin use in trial of labor after cesarean delivery.
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Footnotes
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PII S0029-7844(00)01171-6
Received June 5, 2000.
Received in revised form September 26, 2000.
Accepted October 12, 2000.
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References
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1. American College of Obstetricians and Gynecologists. Vaginal delivery after previous cesarean delivery. ACOG practice bulletin no. 2. Washington DC: American College of Obstetricians and Gynecologists, 1999.
2. Zelop CM, Shipp TD, Repke JT, Cohen A, Caughey AB, Lieberman E. Uterine rupture during induced or augmented labor in gravid women with one prior cesarean delivery. Am J Obstet Gynecol 1999;181:882–6.[Medline]
3. Johnson C, Oriol N, Flood K. Trial of labor: A study of 110 patients. J Clin Anesth 1991;3:216–8.[Medline]
4. Grubb DK, Kjos SL, Paul RH. Latent labor with an unknown uterine scar. Obstet Gynecol 1996;88:351–5.[Abstract]
5. 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.[Medline]
6. Naef RW, Ray MA, Chauhan SP, Roach H, Blake PG, Martin JN. Trial of labor after cesarean delivery with a lower-segment, vertical uterine incision: Is it safe? Am J Obstet Gynecol 1995;172:1666–73.[Medline]
7. Adair CD, Sanchez-Ramos L, Whitaker D, McDyer DC, Farah L, Briones D. Trial of labor in patients with a previous lower uterine vertical cesarean section. Am J Obstet Gynecol 1996;174:966–70.[Medline]
8. Shipp TD, Zelop CM, Repke JT, Cohen A, Caughey AB, Lieberman E. Intrapartum uterine rupture and dehiscence in patients with prior low uterine segment vertical and transverse incisions. Obstet Gynecol 1999;94:735–740.[Abstract/Free Full Text]
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Abstract
Materials and Methods
