Effects of Patient-Controlled Epidural Analgesia on Uterine Electromyography During Spontaneous Onset of Labor in Term Nulliparous Women

Abstract

Objective:

To investigate the effect of patient-controlled epidural analgesia (PCEA) on uterine electromyography (EMG) activity in term pregnant women during labor.

Methods:

Nulliparous pregnant women in spontaneous term labor (N = 30) were enrolled (PCEA group, n = 20 and control group, n = 10). Five time periods (30 minutes each) were defined for noninvasive abdominal recordings and analysis of uterine EMG activity, that is, period I: before PCEA treatment with 2-cm cervical dilation; periods II to IV: each period successively at 30, 60, and 120 minutes after PCEA; and period V: second stage of labor with cervix at 10 cm dilation. Control patients without PCEA were monitored during the same times. The number of bursts/30 min, power density spectrum peak frequency, mean amplitude, and duration of uterine EMG bursts were measured to assess uterine EMG activity. Maternal, fetal, and labor characteristics were also recorded. Data were analyzed by analysis of variance followed by other tests.

Results:

Electromyography parameters are significantly lower (P < .001) after PCEA (periods II to IV) compared to controls but similar between groups by period V (P > .05). Also, patients with PCEA have a slower rate of cervical dilation (P < .003, period IV only) and longer labor in both stage 1 and stage 2 (P < .05). All patients have similar (P > .05) positive labor outcomes.

Conclusions:

Patient-controlled epidural analgesia initially suppresses uterine EMG and slows cervical dilation thereby prolonging labor. However, the EMG activity recovers with labor progress with no effects on delivery outcomes.

Keywords

patient-controlled epidural analgesia (PCEA)uterine electromyography EMG cervical dilation duration of labor

Introduction

Myometrial activation, required for effective contractions and true labor at term or preterm, is characterized by endocrine and molecular changes leading to an increase in coupling and excitability of the muscle cells and increased responsiveness to oxytocics.^1
–3 These events are thought to lead to progressive preparation of the myometrium, accompanied by dilatation of the cervix, and eventual successful labor and delivery.^4,5 Measurement of EMG activity represents the underlying basis for contractility as measured with any technique. Electrical activity of the myometrium can be monitored noninvasively by measuring the uterine electromyography (EMG) from the abdominal surface.^6

–9 Bursts of electrical signals responsible for contractions are more frequent and their duration more constant during labor.^10,11 Temporal and spectral characteristics of EMG activity also change from pregnancy to parturition.^9,12 The methodology for EMG recording and analysis can directly monitor uterine activity to assess the progress of labor, which directly measures electrical events that produce contractions and it is comfortable, convenient, and accurate when compared to other biochemical and biophysical methods such as standard tocodynamometer (Toco) and intrauterine pressure (IUP).^8,9,13,14 Thus, EMG has been used to identify patients in labor but EMG recordings have not been done systematically throughout labor and there are no studies of the effects of PCEA on EMG activity.

Labor, defined as regular forceful contractions of the uterus accompanied by cervical dilation, can be a painful experience for some patients. The degree of pain experienced and the quality of pain relief affect patient’s satisfaction with the birthing process and may have long-term emotional and psychological effects.¹⁵ Presently, epidural analgesic techniques are the gold standard for intrapartum labor pain relief.¹⁶ Patient-controlled epidural analgesia (PCEA) has now become established and a well-accepted technique providing pain relief during labor.¹⁷ Nevertheless, in spite of the proposed benefits and increased use of intrapartum epidural analgesia, and due to the different methods and indications, the effects of epidural labor analgesia on uterine contractions, progress of labor, the mode of delivery, and labor outcomes have generated considerable discussion. There are still debates in the obstetric and anesthesiology communities about the usefulness and problems associated with this treatment, such as prolongation of labor, increases in cesarean section, and increased instrumental deliveries.^18
–20 Other studies show that anesthetics suppress myometrial contractility in vivo²¹ and in vitro.²² It is possible that PCEA could inhibit uterine EMG contractile activity during labor and thereby prolong labor.

Uterine contractions depend upon the underlying electrical activity of the myometrium.²³ Thus, measurement of uterine EMG directly predicts the contractile ability of the uterus, and EMG has been used to identify patients in labor but EMG recordings have not been done systematically throughout labor. In addition, there are still no comprehensive studies of the effects of epidural analgesia, one of the most used techniques in obstetrics, on uterine electrical events during labor and delivery and few studies that have examined the effects of agents which could alter electrical function during labor. The aims of this study are to define the impact of epidural analgesia on uterine electrical activity to assess labor progress and provide an understanding of the trends in labor, clinical treatment, and neonatal well-being at birth.

Materials and Methods

Patients

This observational study utilized term nulliparous pregnant women. Data from patients who underwent cesarean section were not used for analysis based on several considerations, including those of fetal well-being and the subjective assessment of labor progress. This study was carried out on a total of 30 nulliparous women with ages <35 years and a gestational age of 37 to 41 weeks, calculated from the date of the first day of the last menstrual period and confirmed by ultrasound scan. Women were recruited from the delivery ward of the Guangzhou Women & Children’s Medical Center. The study was approved by the Institutional Review Board of the Guangzhou Women and Children’s Medical Center (#2013080905).

All women had singleton pregnancies with spontaneous onset of labor. For all patients, maternal age (years), body mass index, gestational age, duration of first stage of labor, and duration of second stage of labor were recorded. We also recorded cervical dilation in control and PCEA-treated patients during EMG recording by digital examination in stage 1 of labor until stage 2 when dilation was at 10 cm, newborn Apgar score at first and fifth minutes, and newborn weights. Women with any of the following were excluded: (1) unsure of gestational dates; (2) women with medical complications of pregnancy including hypertension, cholestasis, gestational diabetes, and pregestational diabetes; (3) multiple gestations; (4) patients on other forms of pain medication or patients who began the study with no PCEA and then requested it later in stage 1 of labor; and (5) malpresentations. No data were used for the analysis from patients who were treated with oxytocin and/or ultimately underwent cesarean section. A total of 37 patients were recruited for the study: 5 patients were excluded because of oxytocin treatment and 2 patients because of cesarean sections. These data were not included in the study, as there were not enough patients to adequately evaluate effects of oxytocin or cesarean section on uterine electrical activity in spontaneous labor.

Patients were enrolled into 2 groups. The PCEA group consisted of 20 patients who received PCEA during term labor with cervical dilatation of 2 cm and regular contractions.²⁴ The control group included 10 control patients with similar cervical dilatation in labor without PCEA or any pain medication. Before the establishment of labor epidural analgesia, an intravenous drip with 7 mL/kg of lactated Ringer solution was infused over 20 minutes after maternal request for pain relief and informed consent. In other words, the patient’s participation in either control or PCEA group was by self-selection after discussion of pain with their attending physician. The patients in this study were not randomly assigned to groups. Patients received a first analgesia agent of 0.1% levobupivacaine with 5 μg sufentanil, in normal saline for a total of 10 mL via an epidural catheter inserted at the lumbar spine (L2-L3and L3-L4). Analgesia was then maintained throughout labor and delivery with PCEA using a continuous epidural infusion with a 5 mL/h basal infusion rate and 5 mL patient-controlled analgesia boluses of 0.0625% levobupivacaine with 0.4 μg/mL sufentanil, 240 mL in total with an analgesia pump with a 15-minute lockout interval (15 mL/h limit). When patients entered second stage of labor, PCEA was usually temporarily discontinued until delivery, per standard protocol at this institution, during the advanced phase of labor just prior to delivery when active patient participation by contraction of the abdominal muscle is required. For each patient, pain intensity was assessed using a 10-point visual analogue score (VAS), and according to PCEA treatments and EMG measurements, 5 periods of time were defined (see subsequently).

Electromyography Recording

Uterine EMG activity was recorded noninvasively from the abdominal surface using a uterine EMG instrument as described previously.^6

–11 All patients were also monitored with standard Toco using a standard maternal–fetal monitor (Philips, Avalon FM20, Best, the Netherlands). The EMG signals were recorded by means of 4 Ag-AgCl Beckman differential bipolar electrodes (Shanghai Jun Kang Medical Supplies LTD, Co, Shanghai, China) placed around the navel and 1 reference electrode located on the patient’s hip. Analog EMG signals were digitally filtered to yield a final bandpass of 0.34 to 1.00 Hz to eliminate low- and high-frequency noise while preserving the main contraction power where 98% of uterine electrical activity is found.^6,11 Bursts were identified as continuous groups of spikes with the mean voltage peak values greater than 2 times the mean baseline voltage and were used in the calculations of EMG characteristics and to clearly see and compare uterine voltage peaks at adjacent electrodes. From every recording, EMG data were sampled at 1000 Hz and only the bursts of uterine electrical activity occurring during verifiable contractions as observed with the Toco were analyzed using Chart 4.0 software (AD Instruments, Castle Hill, Australia). Patients were monitored continuously for 30 minutes for any given time at 5 periods (periods I-V). For each PCEA-treated patient (PCEA group, n = 20), 5 time periods (30 minutes each) were defined for measurements of EMG: period I: 30 minutes before treatment with cervical dilatation of 2 cm in first-stage labor; period II-IV: each period successively 30, 60, and 120 minutes after PCEA in first-stage of labor; and period V: second stage of labor, cervix 10 cm. Thus, EMG was recorded periodically (periods I-V) for 30 minutes during the first and second stage of labor until immediately prior to delivery. Control patients (control group, n = 10) with no treatment were monitored during the same times. The EMG signals were collected and recorded using an online computer with data acquisition and analysis software, which applied a Fourier transformation to the uterine electrical data in order to calculate the EMG burst analysis. The EMG burst parameters for analysis including number of bursts/30 min, power density spectrum (PDS) peak frequency, burst mean amplitude, and burst duration were used to assess the variation in uterine EMG in 5 time periods, which were chosen based on previous publications.^6,7,10,25 All the EMG recordings and analysis are done by experienced and trained investigators. The sample size (number of patients needed for this study) was determined from previous EMG studies where differences in mean EMG burst frequency in labor versus nonlabor were compared and where power was set at 0.80 with an α of −.05 to give a desired sample size of a minimum of 5 patients/group.¹¹

Statistical Analysis

Demographic and obstetric data were collected and are presented as mean ± standard deviation or median values (minimum and maximum). Data were analyzed by SPSS software for Windows version 13.0, using parametric and nonparametric tests where appropriate. We performed the Kolmogorov-Smirnov to test normality of distribution. Various parameters and multiple parts in groups were tabulated and statistically analyzed by analysis of variance followed by student t test or the Mann-Whitney U test. Statistical significance was considered at P < .05.

Results

Demographic Data and Pain Levels

The data used for analysis was obtained from 30 nulliparous pregnant women in term all of who ultimately delivered spontaneously by the vaginal route. The demographic and obstetrical characteristics of all pregnant women are shown in Table 1. No significant differences (P > .05) were found in the control versus PCEA group, including maternal age, body mass index, gestational age at enrollment, or number of previous pregnancies.

Table 1.

Demographic and Clinical Data.^a

	Group I (PCEA group), n = 20	Group II (Control group), n = 10	P Value
Maternal age, years	29.05 ± 2.63	29.10 ± 2.42	.05
Maternal BMI	28.08 ± 1.13	28.06 ± 1.01	.05
GA at enrollment, weeks	39 (37-40)	39 (37-40)	.05
Newborn’s weight, g	3462.62 ± 400.34	3458.83 ± 406.05	.05
Apgar score first minute	9 (8-10)	9 (8-10)	>.05
Apgar score fifth minute	10 (9-10)	10 (9-10)	>.05

Abbreviations: GA, gestational age; BMI, body mass index; SD, standard deviation; PCEA, patient-controlled epidural analgesia.

^a Data are reported as mean ± SD or median (min-max). Demographic characteristics of women enrolled in 2 groups. Group I = PCEA group, group II = control group. Data = mean ± SD or median (min-max). P values represent differences between groups. Shown are also the mean values for the newborn weights for the control and PCEA-treated patients and also the Apgar scores presented as median (min-max) at the first and fifth minute.

Patients who received PCEA compared to untreated control patients have significantly lower (P < .001) maternal pain and higher maternal satisfaction during all periods. Control patients had moderate VAS values throughout first stage of labor with higher values during second stage. In PCEA-treated patients, the VAS values were significantly lower during initial steps of treatment (P < .001) and progressively increased to higher values during second stage of labor but were still significantly below (P < .001) the control levels.

Electromyography

Figure 1 shows typical examples of EMG activity recorded during 5 time periods from a control patient and a patient who received PCEA. Analysis of the EMG activity in control patients revealed EMG burst number per unit time gradually increased and was highest during second stage of labor (Figure 2). In patients treated with PCEA, there was a significant reduction (P < .001) in frequency of bursts/30 min after PCEA treatment compared to controls and thereafter burst frequency gradually increased and was not significantly different (P = .083) from controls during second stage of labor. The PDS peak frequency (frequency of spikes within a burst) gradually increases with labor progress in control patients (periods I to V), and control group has significantly higher (P < .05) values than the PCEA group (periods II to IV), but there was no significant difference (P = .705) with highest PDS peak frequency in groups during second stage of labor (Figure 3). Similar patterns of EMG activity were observed in analysis of the burst amplitudes (Figure 4) and duration (not shown) with significantly lower values observed in the PCEA-treated patients except during second stage of labor where EMG values were not different (P > .05) from controls. Thus, these results show all EMG parameters are initially significantly depressed by PCEA treatment but that activity gradually recovers until there is essentially no difference between control and PCEA values during second stage of labor.

Cervical Dilation and Duration of the Labor

The cervical dilatation (cervical os diameter, cm as measured digitally) was assessed in the labor ward and performed by the same examiner, a physician in service on the labor ward with many years of experience in dealing with patients in the labor. During periods II to V, the cervix of both the control and the PCEA-treated patients progressively increased in dilation and were similar (P > .05) except period IV, where PCEA cervical dilation values were significantly (P = .003) lower than the control patients. However, cervical dilation was again similar (P > .05) for control versus PCEA-treated patients during period V.

The duration of labor, including time (in minutes) during first stage (from 2 cm cervical dilatation to the starting of the second stage of labor) and time of second stage of labor were significantly longer in the PCEA-treated group compared to the controls. In control patients, the first stage of labor was 386.4 ± 86.5 minutes compared to 469.1 ± 89.9 minutes for PCEA-treated patients (P = 0.023). Similarly, the second state of labor was significantly longer (P = .035) in PCEA-treated patients (controls = 35.1 ± 15.8 minutes; PCEA = 51.95 ± 21.185 minutes).

Fetal Heart Rate, Apgar Scores, and Newborn Weights

The fetal heart rate (FHR) in the PCEA-treated patients temporarily declined in period II following PCEA compared to controls (controls vs PCEA = 140 ± 5.0 bpm vs 134 ± 3.0 bpm) then increased. During the periods I and III to V, there were no significant difference (P > .05) in FHR in controls versus PCEA-treated patients. However, overall, the changes in FHR are within the normal range from 120 to 160 bpm during labor. Shown in Table 1 are the newborn weights of the controls and PCEA-treated patients following delivery. There were no significant differences (P > .05) in the newborn weights and Apgar scores at the first or fifth minute between the control and the PCEA groups.

Discussion

This study systematically analyzed uterine electrical activity (EMG) during early to advanced stages of labor and demonstrates the effect of an agent, in this case PCEA, which suppresses activity and delays labor. Most importantly, PCEA-treated patients obtaining pain relief have decreased EMG activity following application during the first stage of labor but recover with progress of labor and become similar to controls during the second stage of labor. Similarly, PCEA-treated patients have delayed cervical ripening and initially reduced FHR. These studies indicate that PCEA suppresses uterine and cervical function and thus delays labor. Nevertheless, all pregnant women in treated and untreated groups have positive labor outcomes and good newborn Apgar scores.

The PCEA substantially relieves maternal pain as shown by reduced VAS pain scores of about 75% of that of controls in first stage of labor and a reduction of about 50% during the second stage. These results demonstrate PCEA can significantly alter the perception of pain in women in labor and thereby provide pregnant women with a more comfortable delivery.

Uterine electrical signals are directly responsible for contractility of the uterus.^23,26 In this study, bursts of uterine electrical activity corresponded to uterine contraction events and confirm that monitoring uterine EMG is a viable alternative to bulky, unreliable tocodynamometers and invasive IUP catheters.^6,12,27 There are many studies that show that EMG activity gradually increases prior to preterm and term.^8,9,28
–30 In the present study, uterine EMG burst characteristics were examined throughout the first and second stages of labor and estimated in the same patients. Measurable increases in the above-mentioned EMG burst parameters occur during labor in patients without labor analgesia in this present study, which may be explained by increases in energy of the electrical activity and a rise in the high-frequency content of the action potentials by the changes that occur in the electrical properties of the myometrium during labor to produce more forceful contractions.³

In this study, the EMG recordings for the control versus the PCEA-treated patients are not exactly taken during the same time frames because PCEA lengthens the duration of the first and second stages of labor. Nevertheless, we believe that our EMG records and analysis are representative of the activities and effects of PCEA during both stages of labor. In this study, reduced uterine electrical activity was found after PCEA. This may explained by the action of local anesthetics on ion exchange and excitability of the myometrium and an overall decrease in uterine activity. According to some studies, local anesthetics in vitro²¹ also suppress myometrial contractility, and in vivo studies²² with epidural bupivacaine have also demonstrated an effect to slow uterine activity. When patients entered second stage of labor, PCEA was usually temporarily discontinued until delivery. This discontinuation may in part explain why EMG activity resolves during the second stage of labor. Our present studies clearly demonstrate uterine activity resolves with time after starting PCEA and remains similar to control levels found in untreated patients during the second stage of labor. However, the mechanism by which the transient reduced EMG parameters lead to recovery is not evident. Our study emphasizes the importance of uterine electrical activity for progress of labor because EMG activity is significantly depressed by PCEA and this results in a longer duration of labor. No previous study has methodically analyzed EMG activity during the first and second stages of labor with PCEA or other agents that inhibit contractility.

Our study shows a slower rate of cervical dilation after PCEA (period IV) with depressed EMG activity. Period IV includes some patients with 6 cm cervical dilation values (ie, during the active phase of labor as defined by other obstetrical conventions), and thus PCEA may prolong the latent phase of labor. This may suggest that reduced mechanical activity of the uterus due to decreased EMG leads to reduced cervical changes or that epidural analgesia may cause a decrease in concentrations of hormones or endogenous agents known to augment uterine activity or influence cervical changes. Rahm and colleagues³¹ demonstrated lower plasma oxytocin concentrations 60 minutes after initiation of epidural analgesia. Behrens and colleagues³² observed women who received epidural analgesia during the first stage of labor had a decrease in the release of prostaglandin F2, a hormone known to increase uterine activity, and prostaglandins are known to be involved in cervical dilation and are used clinically for this purpose. Also, the present study shows significantly longer duration of first stage of labor in patients treated with PCEA (about 83 minutes longer), which is the result of decreased uterine activity revealed by EMG. This may suggest that the patients treated with PCEA may need to receive more oxytocin to aggressively stimulate uterine electrical activity for the progress of labor, and this may be consistent with the observation from other studies that the incidences of oxytocin augmentation are higher after epidural analgesia.³³ Effective epidural analgesia prolongs the second stage of labor (17 minutes longer in our study), which is consistent with a delay of 15 to 30 minutes found in the literature.^18,19,34,35 Why the second stage is prolonged after PCEA, when EMG activity recovers during this time frame, is not clear but may be due to reduced inertia of the muscle during recovery of EMG. Perhaps this longer labor with PCEA could also be due to difference in fetal position. Liebermann et al³⁶ suggest that there is a strong association of epidural analgesia with fetal occiput posterior position during labor. However, it appears that there was no increase in adverse maternal or neonatal outcomes owing to increased labor time with PCEA as shown in our study and other studies.^37,38

This study lacks the statistical power to satisfactorily examine all aspects of PCEA during delivery and does not include effects of oxytocin and lacks inclusion of patients who ultimately deliver by cesarean section and omits other confounding factors. It would be interesting to study these groups in the future. Following the results of this study, it is expected that uterine contractile stimulants would increase uterine EMG to advance delivery, and other uterine suppressants would decrease both events and prolong labor. Further, our study does not show exactly how much PCEA each patient used during the trial and whether there are differences in rate of self-administration. These are factors that should also be considered in any additional studies.

In summary, this study demonstrates that PCEA initially reduces uterine EMG activity and thereby prolongs labor. However, the EMG activity recovers with labor progress with no effects on delivery outcomes. Uterine EMG recording is a noninvasive method to monitor the uterine activity and should be extremely helpful in diagnosis of the progress of labor and assist in analysis of interventions.

Footnotes

Acknowledgments

We thank the investigators who participated in the study and nurses who assisted in patient care during the course of this study.

Authors’ Note

This study has not been published but an abstract of this study was presented at the Annual Meeting of the Society Reproductive Investigation (SRI) in March 2014.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by funds from the Guangzhou Women & Children’s Medical Center to Huishu Liu.

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