Also, the reference lists of the retrieved studies and recent reviews were manually checked to avoid missing any studies meeting the inclusion criteria. Uterine rupture was defined as a disruption of the uterine muscle extending to, or involving the uterine serosa, or disruption of the uterine muscle with extension to the bladder or broad ligament non-reassuring fetal heart rate, abdominal pain, vaginal bleeding, signs of intra-abdominal hemorrhage, hematuria, disengagement of fetal presentation, and signs of maternal shock [ 19 , 20 ].
Two independent reviewers performed the double-extraction of the data and cross-checked the results for the discrepancy, which were discussed for correction. A third independent reviewer assessed the coding for accuracy by randomly selecting and recoding five articles and examining potential outliers in the data. The authors were contacted by e-mail and relevant data were requested if these values were not reported so as to collect the complete dataset. In the case of no feedback, the studies with missing information were abandoned.
In order to evaluate the effect of oxytocin, studies were grouped according to those that used oxytocin and those that did not. To explore the factors likely to enhance the effect on uterus, studies were grouped as follows: those reporting on oxytocin augmentation among women with spontaneous labor, and those reporting on women who had successfully induced labor.
We calculated the usage rate of oxytocin, rate of VBAC, and rate of uterine rupture by the number of TOLAC, the number of spontaneous delivery, the number of induction labor, the number of VBAC, the number of patients using oxytocin, and the number of uterine ruptures. Due to the anticipated heterogeneity, the random-effects model or fixed-effects model were used to calculate the overall effect size.
Also, we used a two-sample Z test to compare the difference in synthetic rates between groups. Heterogeneity was tested using the I 2 statistic and Q test. Sensitivity analyses and meta-regression were used to explore the potential sources of heterogeneity. Besides, the critical evaluation of the bias risk of the included studies was conducted by two independent reviewers using the Newcastle-Ottawa Scale NOS [ 22 ].
In addition, all statistical analyses were conducted using Stata We evaluated the quality of evidence for each outcome across studies using four levels high, moderate, low or very low confidence according to the Grading of Recommendations Assessment, Development and Evaluation GRADE criteria [ 23 ].
The summary of the screening process is presented in Fig. A total of 36, women had spontaneous delivery, and 11, had induced labor. In the spontaneous delivery group, 11, women had successful VBAC, women used oxytocin augmentation, and women presented with uterine rupture. Among those with induced labor, had successful VBAC, used oxytocin induction, and 41 presented with uterine rupture in the induction of labor.
In addition, in 11 studies, the uterine rupture was clearly described, while it was unclear in 3 studies [ 24 , 25 , 26 ]. Other demographic and clinical information for each study are shown in Table 1. The rates of VBAC, oxytocin use and uterine rupture in women with spontaneous and induction labor were listed in Table 2.
In addition, the methodological quality of the studies assessed by NOS is presented in the Supplement materials.
Most included studies were scored with six or more stars, representing high quality. According to the including criteria, a literature search was conducted through. Finally, 14 relevent studies were included after screening. The pooled usage rate of oxytocin, rate of VBAC and rate of uterine rupture in spontaneous delivery group were To explore possible sources of heterogeneity, we calculated the synthetic effect size in the spontaneous delivery group and induced labor group; 3 studies which did not have a clear definition of uterine rupture were excluded [ 24 , 25 , 26 ].
The pooled usage rate of oxytocin, rate of VBAC and rate of uterine rupture in spontaneous delivery were However, heterogeneity obviously increased after re-analyzing. To assess the influence of outliers, the standardized residual was examined for all studies. We conducted the sensitivity analysis by removing one study at the time to evaluate the weights of individual studies on the pooled SMDs.
S4 showed that sensitivity analysis was relatively robust for the meta-analysis, with no reverse outcomes see Supplementary materials. Despite high methodological quality, direct evidence, and precision, the included studies were characterized by moderate heterogeneity, thus providing the evidence to understand the way of moderate quality GRADE rating system see Supplementary materials.
The pooled rates of uterine rupture in women who were using oxytocin and those who were not in TOLAC were 1. On the basis of the previous results, we calculated the pooled rates of uterine rupture in oxytocin augmentation among women with spontaneous labor and those with induction of labor, which were 1. The pooled rates of uterine rupture in oxytocin augmentation among women with spontaneous labor and those with induction of labor were 1.
ES, effect size; CI, confidence interval. The primary purpose of the current meta-analysis was to systematically identify the effect of oxytocin on the risk of uterine rupture in TOLAC. In addition, we also explored differences in the usage rate of oxytocin, rate of VBAC between spontaneous delivery and induction of labor. The results showed that women with spontaneous delivery had a higher rate of VBAC and lower risk of uterine rupture than those with the induced labor.
Moreover, we compared the risk of uterine rupture in augmentation among women with spontaneous labor and women who had a successful induction of labor whilst controlling for potential factors, which revealed no significant statistical differences. These data revealed that the process labor induction or cervix condition might influence the effect of oxytocin on the uterine. In our study, the VBAC rates in women with spontaneous delivery and labor induction were We also found that the VBAC rate was significantly different between women with spontaneous and induction labor.
Some mechanisms, such as inflammatory cytokines, regulation of endocrine hormone, and mechanical stimulus, may contribute to these differences [ 41 ]. Besides, we found that the rates of oxytocin usage in women with spontaneous and induction labor were However, we were unable to obtain enough information to separately analyze these variables.
Our results demonstrated a low rate of uterine rupture in women attempting TOLAC with spontaneous versus induced labor 0. A previous study found that the rate of uterine rupture was from 0. Thus, we concluded that the rate of uterine rupture tends to vary from study to study, which may be partly due to the way uterine rupture is defined in researches.
Generally speaking, uterine rupture includes complete uterine rupture and incomplete rupture uterine scar dehiscence. This study took a definition of complete uterine rupture. However, incomplete uterine rupture is defined as a disruption of the uterine muscle with intact uterine serosa, which is mostly asymptomatic. Different conditions may lead to different outcomes.
Complete uterine rupture is associated with severe maternal risk of hemorrhage with a need for transfusion, hysterectomy and perinatal risks of anoxoischemic encephalopathy, and even fetal death morbidity and mortality. In addition, it remains one of the most catastrophic obstetrical emergencies [ 45 ].
However, uterine dehiscence has little to no consequence on immediate maternal or neonatal morbidity and is only detected in cases of emergency cesarean section [ 46 ]. To avoid the effect of ambiguous definition on heterogeneity, we have calculated the pooled effect by excluding the studies that did not have a clear explanation of uterine rupture.
The results showed that heterogeneity obviously increased, which proved that heterogeneity did not come from the ambiguous definition. Moreover, an unavoidable source of heterogeneity may come from the medical level in different areas. In a general way, senior or specialized hospitals may have more experience and the ability to prevent and treat a uterine rupture. In contrast, junior or comprehensive hospitals may have a higher rate of uterine rupture. It may cause the main heterogeneity of these results, but we need more detailed information to deal with this issue.
Consequently, we compared the rate of uterine rupture in women using oxytocin and not using oxytocin in TOLAC 1. According to the previous researches, the association between oxytocin and uterine rupture remains unknown. Contrary, Landon et al reported that augmentation and induction with oxytocin were associated with an increased risk of uterine rupture [ 6 ].
In the studies of Cahill et al, there was a dose-response relationship between maximum oxytocin dose and risk of uterine rupture. This provided an explanation for why women who had more labors induced with oxytocin were at greater risk of uterine rupture than those with spontaneous labor.
To further investigate how oxytocin increases the risk of uterine rupture, we compared the risk of uterine rupture in labor augmentation among women with spontaneous labor and women with successfully induced labor. We found no statistical significance between groups, which supported the premise that the process of induction labor or individual cervix condition may change the effect of oxytocin and increase the risk of uterine rupture.
Previous researches reported that other potential factors, such as induction of labor with prostaglandin or Foley catheters, could also increase the risk of uterine rupture compared to spontaneous delivery [ 50 , 51 ]. The process of induction may make scarred uteruses more sensitive and brittle. Our study also showed that neither oxytocin nor other way of induction could indirectly increase postpartum complications; however, this needs to be further investigated by future studies.
Another possible cause of increased risk may be the individual cervix condition. Unfavorable cervix could enhance the difficulty of parturition, which in turn could increase the chances of exposure to risk factors. The Bishop score is commonly used in most clinical evaluations for the ripeness of the cervix. A previous study reported that women who underwent induction with a favorable cervical score had a lower rate of uterine rupture [ 52 ].
While this assessment tool is not perfect in its repeatability and objectivity, currently it is the best option [ 53 ].
More suitable evaluation tools need to be developed to help clinical observation. The present meta-analysis has some limitations. First, we could only make the conclusion on the risk association between oxytocin and uterine rupture. Thus, more studies are needed in the future. Second, the high heterogeneity among the included studies could not be ignored. Though we have excluded the influence of the diagnosis, other potential factors, such as maternal age, ethnicity, BMI, gestational age, infant birth weight, higher admission bishop score, medical level, and so on could also be relevant.
However, it was not possible to obtain more detailed information from the included studies. Though it is common for meta-analyses of observational studies to present high heterogeneity, more studies in the future are necessary. In addition, we have made the Newcastle-Ottawa Scale to evaluate and ensure the quality of the included studies so as to reduce bias as much as possible. Overall, our study has demonstrated the risk association between oxytocin use in TOLAC and uterine rupture.
These data were compared between the groups. Any other adverse events like chest pain, nausea, vomiting, and flushing were noted. There was significant rise in heart rate and significant decrease in mean arterial pressure in bolus group compared to infusion group. No such complications were found in infusion group. Bolus oxytocin at a dose of 3 IU over 15 seconds and infusion of oxytocin at a dose of 3 IU over 5 minutes have comparable uterotonic effect.
However, the bolus regime shows significantly more adverse cardiovascular events. Oxytocin is the most commonly used uterotonic agent in obstetrics. It is routinely administered after both normal and operative delivery to initiate and maintain adequate uterine contractility for minimizing blood loss and preventing postpartum hemorrhage.
Larger dose of oxytocin injected rapidly is known to produce various adverse effects such as hypotension, nausea, vomiting, chest pain, headache, flushing, myocardial ischemia, ST-T segment changes, pulmonary edema, severe water intoxication, and convulsion. We aimed to compare the hemodynamic effects heart rate, mean arterial pressure, arrhythmias , uterine contraction, and adverse events chest pain, flushing, nausea, and vomiting of equivalent doses of oxytocin as IV bolus versus IV infusion.
This randomized, double-blind, active controlled trial was started after obtaining the clearance from the Institute's Ethics Committee and written informed consent from all patients. Patients with active labor pain, ruptured membrane, multiple gestation, cardiovascular instability, preeclampsia and eclampsia, diabetes mellitus, and placenta previa were excluded from this study. The patients were instructed to avoid solid food for 6 hours and allowed to drink plain water up to 2 hours before the operation.
All the patients were premedicated with slow metoclopramide 10 mg and ranitidine 50 mg IV. The procedure of SA was explained to all patients. Randomization was done following a computer-generated random numbers. Allocation concealment was ensured with sealed opaque envelope. Patients concerned as well as data collector were blind to the mode of administration of oxytocin. Both the groups received infusion; one of them received oxytocin among it to make similarity between them. Then 12 mg hyperbaric bupivacaine 0.
The patients were then made supine with left lateral uterine displacement using a wedge. Multichannel monitor was attached. Surgery was allowed to proceed after achieving a T6 sensory level to pinprick.
Oxytocin was administered as per the group allocated after childbirth. Uterine tone was assessed by obstetrician same obstetrician for all cases and designated as adequate or inadequate. Patients having a fall in MAP before the administration of oxytocin were treated with IV bolus of mcg phenylephrine and were excluded from the study. HR was measured at second interval up to 2. MAP was measured at 1-minute interval up to 5 minutes, then at 7 and 10 minutes.
Any EKG changes were monitored. If uterus was not adequately contracted after 3 minutes, oxytocin 3 IU IV was given as rescue dose. A maximum of 2 rescue doses were given. If still the uterus was not contracted, carboprost tromethamine 0. After the study period patients received a maintenance IV infusion of oxytocin 0.
Numerical data were analyzed with Student's t -test and categorical data were analyzed with Chi-square test. The study was conducted from January to June Eighty patients were recruited for the study. Both the groups were comparable demographic data [ Table 1 ].
There was a failure of spinal anesthesia procedure in 3 patients and so they received general anesthesia. Three patients developed significant hypotension and required vasopressor prior to oxytocin administration; four patients required rescue uterotonic other than oxytocin.
Ten patients violated the study protocol thus and were excluded from analysis. In case of infusion group heart rate increased by about 10 beats per minute at 60 seconds of starting infusion, gradually decreased to almost basal level at 10 minutes. For elective caesarean section, a slow 0. For the labouring parturient a slow 3 IU bolus of oxytocin, followed by an infusion of 5 to 10 IU. These doses represent a starting point in the control of postpartum haemorrhage after caesarean section and do not reduce the need for mandatory active observation of the clinical situation, to detect situations that require additional doses of oxytocin or other uterotonic drugs.
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