Effects of different bupivacaine concentrations with dural puncture epidural technique for labor analgesia: a prospective randomized controlled trial

Abstract

Background

Dural puncture epidural (DPE) is a newer and more advantageous method in labor analgesia. It provides a faster analgesia onset and higher-quality block compared to the conventional epidural (CE) method, while causing fewer adverse effects than the combined spinal-epidural (CSE) technique. This study aims to compare the effects of bupivacaine at different concentrations, but equal volumes administered via DPE on the mother, fetus, and labor process, and reduce total bupivacaine requirement and its potential side effects.

Methods

Seventy ASA II primigravid pregnant women with cervical dilatation between 4 and 6 cm were included in the study. Participants were randomly divided into two groups. Group 1 received a high concentration of bupivacaine (0.125%) + 2 mcg/mL fentanyl; Group 2 received a low concentration of bupivacaine (0.0625%) + 2 mcg/mL fentanyl, both using DPE. The numeric rating scale (NRS) score was aimed to be < 4. The total amount of bupivacaine and fentanyl administered through the epidural catheter, the time between applications, the time between applications and birth, the number of doses administered, complications, maternal vital signs, fetal heart rate and maternal satisfaction were recorded.

Results

The mean amount of bupivacaine administered was 31.7 ± 7.6 mg in Group 1 and 15.1 ± 3.4 mg in Group 2, showing a significant difference (P = 0.001, Mean ± SD, Student’s t test). There were no significant differences in NRS scores, duration between doses, duration between doses and delivery, satisfaction, and complications.

Conclusion

This study compared the effects of different bupivacaine concentrations with DPE and found that using low-concentration bupivacaine (0.0625%) for labor provides adequate analgesia without increasing complications or delivery time while reducing the amount of bupivacaine needed.

Trial registration

Registration number: NCT05499234. Registration date: 2022-08-02 (Retrospectively registered). Registration URL: https://clinicaltrials.gov/ct2/show/NCT05499234.

Background

Conventional epidural (CE) has been used in labor analgesia for years, now considered the gold standard [1]. Dural puncture epidural (DPE) provides a faster, higher-quality block than CE and causes fewer adverse effects, such as hypotension, maternal pruritus, and fetal bradycardia, than the combined spinal-epidural (CSE) [2, 3]. In addition, DPE shows no increase in adverse effects compared to CE[4]. These advantages have led to DPE gaining popularity in labor analgesia in recent years. While there are many studies on the use of different concentrations of local anesthetics in CE[5], only a few studies to date have compared different concentrations of local anesthetics using the DPE technique. We aimed to compare the effects of different concentrations of bupivacaine on labor analgesia to determine the appropriate clinical dosage and minimize excessive administration and potential adverse effects.

Methods

Following the approval of the Istanbul Medipol University Non-Interventional Clinical Research Ethics Committee (Decision No. 562, dated 20/05/2021), our single-center prospective randomized study commenced. The study was also registered in clinical trials on August 1 st, 2022, with registration number NCT 05499234. The principal investigator of this study is Fatma Pınar Uçar. All volunteer participants were included after being informed about the study and signing the Informed Volunteer Consent Form.

Seventy primigravid women in the ASA II risk group, who applied to the Medipol Mega University Hospital Gynecology and Obstetrics Clinic between July 1, 2021, and April 30, 2022, requested epidural analgesia during spontaneous vaginal birth and had a cervical dilation between 4 and 6 cm, were informed of the procedure to be applied.

Patients with pregnancy-related diseases (such as gestational hypertension, gestational diabetes, preeclampsia) and neuraxial block contraindications (skin infection at the site of spinal needle puncture, coagulation disorders, severe hypovolemia, intracranial hypertension, sepsis, presence of neurological deficit, heart valve stenosis, or hypertrophic obstructive cardiomyopathy) were excluded from the study. Patients with fetal malpresentation and fetal anomaly were also excluded from the study.

Patients were randomly divided into two groups of 35 individuals each. With the DPE method, a 20 mL solution consisting of 0.125% bupivacaine + 2 mcg/mL fentanyl was given to the first group (Group 1). The other group (Group 2) received a 20 mL solution consisting of 0.0625% bupivacaine + 2 mcg/mL fentanyl as an initial dose, also using the DPE method. The Numeric Rating Scale (NRS) score was aimed to be < 4 in both groups. Patients with an NRS score of 4 or above after fifteen minutes from the first dose were planned to be administered an additional dose of 10 mL of the first applied solution (containing 0.125% bupivacaine + 2 mcg/mL fentanyl for Group 1, 0.0625% bupivacaine + 2 mcg/mL fentanyl for Group 2). When the NRS score was 4 or above until the moment of crowning, each group continued to be administered an additional dose of 10 mL of its solution. An NRS score of 4 or above 15 minutes after the additional dose would be considered a ‘failed epidural’ and the patient would be excluded. Pain management for these patients is planned with meperidine and paracetamol.

In both groups, the same volume of epidural solution was used at each administration: 20 mL as the initial dose and 10 mL as each additional dose when required. Thus, the groups differed only in bupivacaine concentration, not in the administered volume.

Maternal and fetal monitoring (fetal heart rate, electrocardiography, non-invasive blood pressure measurement, and pulse oximetry) was performed on each patient before, during, and after epidural catheter insertion. Before the induction dose, patients were asked to evaluate their pain between 0 (no pain) and 10 (the worst possible pain), and the NRS score was recorded. After the induction dose, the NRS score was evaluated every 2 min for 15 min. Adequate analgesia was considered as an NRS score < 4. Epidural analgesia was maintained by manual bolus administration when the patient’s NRS exceeded 4. After successful analgesia was achieved the NRS score was assessed on an hourly basis, and patients were additionally instructed to contact the study team if their NRS score reached 4 or above. Before placing the epidural catheter, the patient’s age, weight, body mass index (BMI), blood pressure, heart rate, whether oxytocin was used during birth or not, the amount of cervical dilatation and effacement before the procedure, and fetal heart rate were recorded.

Maternal hypotension, fetal bradycardia, pruritus, nausea, vomiting, and motor block were monitored after each dose. Fetal heart rate < 100/min for more than 10 min was considered fetal bradycardia. Patients who could not complete the spontaneous vaginal birth process and underwent cesarean section were identified. Spontaneous vaginal births were monitored and recorded to determine whether they turned into instrumental births or not.

Epidural was performed with an 18G Tuohy needle, and dura was punctured with a 27G Quincke needle (Espocan + Docking System + Perifix Soft Tip, Braun, Germany).

The total amount of bupivacaine and fentanyl administered through the epidural catheter, the time between applications, the time between applications and birth, as well as the number of bolus doses administered, were recorded. Patients were monitored for post-dural puncture headaches after birth. Motor power was assessed using the Modified Bromage Scale. Systolic blood pressure < 90 mmHg or 20% below the basal value was considered maternal hypotension. In case of hypotension, it was planned to intervene with 5 mg ephedrine. Pruritus was evaluated on a scale between zero and three (0 = absent, 1 = mild, 2 = moderate, 3 = severe). At fifteen minutes after the induction dose and again at the time of epidural catheter removal after delivery, mothers were asked about their satisfaction with the technique applied. Analgesia satisfaction was graded as ‘poor’, ‘moderate’, or ‘good’.

The primary outcome was the total dose of bupivacaine administered during labor. Secondary outcomes included NRS pain scores, number of additional doses administered, incidence of motor block (Modified Bromage Scale), delivery type (spontaneous vaginal or cesarean), maternal satisfaction, and complications such as hypotension, fetal bradycardia, pruritus, and nausea/vomiting.

The primary aim of this study is to reduce the total bupivacaine requirement. In a preliminary pilot study conducted before this trial, the mean total bupivacaine requirement was observed to be approximately 30 mg in Group 1 and 15 mg in Group 2, with standard deviations of 6.84 mg and 3.42 mg, respectively. Based on an expected minimum difference of 5 mg between the groups, assuming a standard deviation of 6.84 mg for Group 1 and 3.42 mg for Group 2, with a two-sided α error of 0.05 and a β error of 0.10 (i.e., 90% power), the calculated sample size was 26 participants per group. To account for potential dropouts or exclusions, we included 35 patients in each group. The trial was completed as planned.

Statistical analysis

All statistical analyses were performed using the SPSS 26 program. All randomized patients were analyzed in the groups to which they were initially assigned. Randomization was performed using computer-generated random number tables, and allocation concealment was ensured via sealed opaque envelopes. The patients, care providers, and outcome assessors were blinded to the group allocation. Descriptive statistics are the mean and standard deviation for continuous variables, and median (minimum-maximum); for categorical variables, they were expressed using numbers and percentage values. Before all analyses, whether the data conformed to normal distribution was evaluated using skewness-kurtosis values, normality tests, and histogram graphs. In determining the differences in mean values between groups, an independent variables T-test or dependent variables T-test was used for variables that complied with normal distribution, whereas the Mann-Whitney U test was used for variables that did not comply with normal distribution. The chi-square test or Fisher’s exact test was used to determine the differences in categorical variables between groups. Accordingly, continuous variables that met the normality assumption are reported as mean ± standard deviation, whereas non-normally distributed data are presented as median (minimum–maximum). P < 0.05 was considered the statistical significance level in all analyses. There were no missing data for the primary or secondary outcomes: the participants were included in the final analysis.

Results

The CONSORT flow diagram was used for the enrollment of the patients during the study period. In comparing the demographic data of the patients and their vital signs before drug administration, no significant difference was observed between the two groups (p > 0.05, Table 1).

Table 1.

Demographic data and baseline vital values (Mean ± SD)

Variables	Group 1	Group 2	p-value
Age (years)	28.8 ± 3.8	28.4 ± 4.2	0.639
Weight (kg)	76.1 ± 10.3	77.6 ± 10.3	0.551
BMI (kg/m2)	27.5 ± 3.1	28.9 ± 4.3	0.124
Systolic Blood Pressure (mmHg)	118.9 ± 10.3	121.7 ± 11.9	0.289
Diastolic Blood Pressure (mmHg)	72.7 ± 9.14	75.3 ± 8	0.216
Heart Rate (beats/minute)	82 ± 8	82 ± 7	0.755
Fetal Heart Rate (beats/minute)	141 ± 7	141 ± 7	0.755

BMI Body Mass Index

Data are presented as mean ± standard deviation (SD). Group comparisons were performed using the Independent Samples t-test. P < 0.05 was considered statistically significant

When oxytocin use between the two groups was compared, it was observed that oxytocin was administered to 28 patients in Group 1 and 24 patients in Group 2. The p-value was 0.274, indicating no statistically significant difference between the groups. When the induction dose applied through the epidural catheter and the time between birth were compared, no significant difference was observed between the two groups. The number of patients requesting only one additional dose between the induction dose and birth was 14 in Group 1 and 13 in Group 2; the number of patients who requested additional doses twice was two in Group 1 and one in Group 2. In comparing the durations between the induction dose and the first additional dose, no significant difference was found. When the duration between the first additional dose and birth was compared, no significant difference was found between the two groups (p > 0.05, Table 2).

Table 2.

Intervals between the induction dose and additional doses. Median (min-max)

Time interval	Group 1		Group 2		p-value
	Patient Number	Duration (min.)	Patient Number	Duration (min.)
Induction dose - Birth	35	130 (30–630)	35	140 (45–390)	0.755
Induction dose − 1 st additional dose	16	110 (15–180)	14	95 (15–190)	0.163
1 st additional dose - Birth	16	80 (15–510)	14	74 (20–270)	0.803

min minutes

Data are presented as median (minimum–maximum). Comparisons between groups were performed using the Mann–Whitney U test. P < 0.05 was considered statistically significant

In reviewing the data of two patients in Group 1 who requested a second additional dose, the durations of one of the patients were recorded as 305 min between the induction and 2nd additional doses, 140 min between the 1 st and 2nd additional doses, and 180 min between the 2nd additional dose and birth. For the other patient, durations were 270 min between the induction and 2nd additional doses, 150 min between the 1 st and 2nd additional doses, and 360 min between the 2nd additional dose and birth. For the single patient in Group 2 who requested a 2nd additional dose, the duration between the induction dose and the 2nd additional dose was detected to be 150 min, the time between the 1 st and 2nd additional doses was 75 min, and the time between the 2nd additional dose and birth was 10 min. No significant differences were found between the two groups when NRS scores before the induction dose and NRS scores 15 min after the induction dose were compared. When the NRS scores were compared after the first additional dose in patients who requested additional doses, no significant difference was detected (p > 0.05, Table 3).

Table 3.

NRS values after drug administration. Median (min-max)

	Group 1		Group 2		p-value
	n	NRS	n	NRS
Before the induction dose	35	9 (7–10)	35	8 (6–10)	0.114
Post-induction dose	35	2 (1–5)	35	2 (1–7)	0.633
After the first additional dose	16	3 (1–3)	14	2 (1–3)	0.609

NRS Numerical Rating Scale

Data are presented as median (minimum–maximum). Comparisons between groups were performed using the Mann–Whitney U test. P < 0.05 was considered statistically significant

At 15 min after the induction dose, one patient in each group was found to have an NRS score above 4. The patient in Group 1 had an NRS score of 5, which decreased to 2 fifteen minutes after the additional dose. The patient in Group 2 had a post-induction NRS score of 7, which decreased to 3 after the additional dose.

In Group 1, 19 patients completed delivery with only the induction dose without requiring an additional dose, while in Group 2, this number was 21. The p-value was calculated as 0.809, and no significant difference was found.

No ‘failed epidural’ was seen during the study, so intervention with meperidine and paracetamol was not needed.

Mild pruritus was observed in one patient in Group 1, and severe pruritus occurred in one patient in Group 2. Other complications such as paresthesia, rate of conversion to cesarean section, nausea, vomiting, maternal hypotension, fetal bradycardia, and post-dural puncture headache were not found to be significantly different (p > 0.05, Table 4).

Table 4.

Comparison of complications between groups

Complications	Group 1 n (%)	Group 2 n (%)	p-value
Paresthesia	5 (14.3)	2 (5.7)	0.232
Cesarean section	4 (11.4)	2 (5.7)	0.673
Nausea	3 (8.6)	2 (5.7)	1
Vomiting	1 (2.9)	0 (0.0)	1
Hypotension	0 (0.0)	0 (0.0)	1
Fetal bradycardia	1 (2.9)	1 (2.9)	1
Post-dural puncture headache	0 (0.0)	0 (0.0)	1

Data are presented as n (%). The Chi-square test was used for comparisons between groups, except for variables with expected cell counts < 5, where Fisher’s exact test was applied. P < 0.05 was considered statistically significant

Cesarean delivery occurred in 4 patients (11.4%) in Group 1 and in 2 patients (5.7%) in Group 2, with no statistically significant difference (p = 0.673). When the patients who underwent cesarean section were excluded to compare the rate of instrumental vaginal birth between the two groups, the remaining 31 patients in Group 1, as well as the remaining 33 patients in Group 2, did not require the use of instruments during labor.

When patient satisfaction with analgesia was evaluated 15 min after the induction dose, it was observed that in Group 1, 4 women reported moderate satisfaction and 31 reported good satisfaction, while in Group 2, 1 woman reported poor satisfaction, 2 reported moderate satisfaction, and 32 reported good satisfaction, P = 0.431, indicating no significant difference. Regarding postpartum satisfaction, it was observed that in Group 1, 2 women reported poor satisfaction, 4 reported moderate satisfaction, and 29 reported good satisfaction, while in Group 2, 1 woman reported poor satisfaction, 1 reported moderate satisfaction, and 33 reported good satisfaction, P = 0.302, also indicating no significant difference.

When the modified Bromage scores of the patients after the induction dose were compared, it was found to be 0 (0–1) in Group 1 and 0 (0–1) in Group 2 (P = 0.539). No significant difference was observed. When the modified Bromage scores after the first additional dose of the patients requesting an additional dose were examined, it was observed as P = 0.367, whereas no significant difference was found. In Group 1, modified Bromage score of 2 was observed in two patients after the first additional dose. No patient with a modified Bromage score of 2 was observed in Group 2. Since the number of patients who requested an additional dose for the second time was 3 in total, no statistical findings could be obtained regarding modified Bromage scores after the second additional dose. The modified Bromage score of 3 patients who needed the second additional dose was observed to be 0 after the second additional dose.

The mean number of requested doses from the placement of the epidural catheter until delivery was observed to be 1.54 ± 0.6 in Group 1 and 1.49 ± 0.5 in Group 2. When the two groups were compared, the p-value was found to be 0.685, indicating no significant difference. Accordingly, since the same concentration of fentanyl was used in both groups, the amount of fentanyl administered through the epidural catheter was 50.8 ± 12 µg in Group 1 and 48.5 ± 11.1 µg in Group 2 (p = 0.416), showing no statistically significant difference between the groups.

The mean total amount of bupivacaine administered throughout labor, including both the initial and all additional bolus doses, was found to be 31.7 ± 7.6 mg in Group 1 and 15.1 ± 3.4 mg in Group 2, with a statistically significant difference between the groups (p < 0.001) (Fig. 1).

Fig. 1.

Comparison of total drug doses between groups

Bars indicate mean values; error bars represent standard deviation. n = 35 per group. p < 0.001, Independent Samples t-test.

The mean difference in total bupivacaine dose between Group 1 and Group 2 was 16.6 mg (95% CI: 13.74 to 19.46; p < 0.001), indicating a statistically and clinically significant reduction in anesthetic requirement with the use of 0.0625% bupivacaine.

Discussion

Although the effects of local anesthetic concentration differences have been compared in other regional analgesia techniques, there is only a few publication about concentration differences in DPE. Thus, in this study, we compared the effects of bupivacaine concentration differences in DPE. At the end of this comparison, no major difference in pain control or complications was observed. We found that the use of low-concentration bupivacaine (0.0625%) in labor analgesia with DPE significantly reduced the total amount of bupivacaine consumption for adequate analgesia.

Previous studies on the CE have recommended that low concentrations of local anesthetic should be used [5]. With this study, we compared the effects of bupivacaine concentration differences on labor analgesia with DPE and managed to reduce the amount of local anesthetic used.

When the NRS scores before and after the induction dose were compared between the two groups, no significant difference was found. This indicates that the use of low-concentration (0.0625%) bupivacaine provides analgesia equivalent to that of high-concentration (0.125%) bupivacaine. The absence of a significant difference in post-administration NRS scores among patients who requested additional doses further supports this finding. The lack of a significant difference in the number of additional doses requested until delivery also indicates that low-concentration bupivacaine provides sufficient analgesia. Furthermore, the absence of a difference in patient satisfaction both after the induction dose and postpartum is another indication that low-concentration bupivacaine ensures adequate analgesia.

The meta-analysis by Halliday et al. suggested that the use of bupivacaine at concentrations higher than 0.08% may prolong the first stage of labor by blocking autonomic nerves responsible for uterine contractions [5]. However, in our study, we found no difference in the effect on labor duration between the use of 0.125% and 0.0625% bupivacaine.

Mohammad et al. compared different bupivacaine concentrations for postoperative pain control using CE and demonstrated that complications were more frequent in the high-concentration (0.125%) group [6]. Halliday et al. also showed that the use of 0.0625% bupivacaine reduced the likelihood of assisted vaginal delivery and cesarean section compared to higher concentrations [5]. In our study, we compared complications between the two groups, including pruritus, paresthesia, rate of conversion to cesarean section, nausea, vomiting, maternal hypotension, fetal bradycardia, and post-dural puncture headache. Although no statistically significant difference was found, some adverse events like paresthesia, nausea, vomiting, cesarean section were numerically more frequent in the high-concentration group. We also noted that in Group 1, two patients had a modified Bromage score of 2, whereas no patients with a modified Bromage score of 2 were observed in Group 2.

A previous study [7] reported that differences in local anesthetic concentration did not affect fetal outcomes. In our study, fetal bradycardia was monitored as an indicator of fetal status, also no differences were observed between the groups.

When the amount of bupivacaine needed at the induction of labor analgesia with DPE and CE is compared, bupivacaine needed with DPE was found to be significantly lower [8]. Therefore, the use of the DPE method was also beneficial in achieving our primary goal of reducing the amount of bupivacaine. According to this study, the amount of bupivacaine providing adequate analgesia in 90% of patients (ED90) at the induction dose with DPE was determined to be 29.3 mg. In our study, we showed that 12.5 mg bupivacaine is sufficient as an induction dose using low-concentration (0.0625%) bupivacaine. The differences between our findings and those of Maeda et al. may be partly attributable to methodological variations. In our study, all patients received bupivacaine combined with 2 µg/mL fentanyl, whereas Maeda et al. used plain bupivacaine without opioids. The opioid additive likely enhanced analgesic efficacy, reducing total local-anesthetic consumption.

Halliday et al. demonstrated that, in the conventional epidural method, the use of 0.0625% bupivacaine resulted in comparable or even better fetal/maternal outcomes compared to higher concentrations, while reducing the amount of local anesthetic used [5]. With this study, we have shown that the same outcome can be achieved with the DPE method as well.

When intermittent bolus with DPE, continuous infusion with DPE, and continuous infusion with CE were compared, it was shown that the total amount of local anesthetic required with DPE + intermittent bolus is the least [9]. It was also found that the development of motor block is less with intermittent bolus than with continuous infusion [10]. For these reasons, we chose to apply intermittent bolus dosing in our study and managed to provide an effective level of analgesia.

For dural puncture, 25, 26, and 27G needles can be used. No significant differences have been reported between 25G and 27G spinal needles in terms of block level, number of additional doses required, or the quality of analgesia [11]. When DPE performed with a 27G needle was compared to the conventional epidural (CE) technique, DPE was still shown to provide faster onset and higher-quality analgesia [12, 13]. Accordingly, in our study, a 27G spinal needle was preferred both to achieve effective analgesia and minimize the risk of post-dural puncture headache.

This study has several limitations. Neonatal outcomes such as Apgar scores, umbilical cord pH, and the need for NICU admission were not assessed. This omission represents a limitation of the present study and should be addressed in future research to fully evaluate neonatal safety. The second limitation is that sensory block levels were not systematically assessed. This limits the ability to correlate analgesic adequacy with dermatomal block height. Because of the small sample size and non-normal data distribution, repeated measurements such as NRS scores and hemodynamic parameters were analyzed separately at each time point rather than using repeated-measures models. Future studies with larger sample sizes may apply mixed-effects or repeated-measures ANOVA to better account for within-subject variability over time.

Conclusions

In our study, it was observed that the same level of analgesia and patient satisfaction was achieved in two groups, without detecting a significant difference in complications and delivery time. While adequate analgesia was achieved with the use of low-concentration bupivacaine, the significant decrease in the amount of bupivacaine used was an important result for our study. Thus, with this study, we concluded that a low-concentration solution is sufficient to provide labor analgesia with the DPE method.

Abbreviations

ASA

American Society of Anesthesiologists

APGAR

Appearance, Pulse, Grimace, Activity, Respiration

BMI

Body Mass Index

CE

Conventional Epidural

CSE

Combine Spinal-Epidural

DPE

Dural Puncture Epidural

NRS

Numeric Rating Scale

Authors’ contributions

Study conception and design: all authorsLiterature search: all authorsData collection: F.P.U., H.G.D., P.K.Data analysis and supervision: P.K., H.A.AWriting of the manuscript: F.P.U., B.Ö.All authors revised the manuscript for significant intellectual content, gave approval for the version to be published, and agreed to be accountable for the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was initiated following the approval of the Non-Interventional Clinical Research Ethics Committee of Istanbul Medipol University dated 20/05/2021 with decision number 562. All volunteers were included in the study after being informed about the study and signing the Informed Consent Form. This study was conducted in accordance with the principles of the Declaration of Helsinki. This randomized controlled trial was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.