Comparative Study of Bupivacaine-Fentanyl versus Ropivacaine-Fentanyl for Epidural Analgesia in Labor.

Background: Labor pain is one of the most intense pains that a woman experiences. Almost 60% of primiparous women described the pain of uterine contractions as unbearable extremely severe or excruciating. Aims: Our study aimed to relieve pain suffering of mother and to decrease fetal acidosis to make the delivery process safer for mother and baby. Settings and Design: Thus, epidural labor analgesia was designed comparing ropivacaine-fentanyl (RF) and bupivacaine-fentanyl (BF) as intermittent bolus technique. Materials and
Methods: Sixty women who requested epidural analgesia having ≥3 cm cervical dilatation were allocated in two groups, one group received RF and the other group received BF. Each group received study drug 16 mL with 50 μg fentanyl and top of 10 mL and 25 μg fentanyl when visual analog scale (VAS) ≥3. The efficacy of analgesia, adverse effects, and obstetric and neonatal outcomes were compared. Statistical Analysis: For skewed data or ordered categorical data, nonparametric Mann-Whitney U-test was used for statistical analysis of two groups. For categorical data, comparisons were made by Pearson's Chi-square test or Fisher's exact test as appropriate (%).
Results: Both groups were comparable in terms of demographic data and obstetric and neonatal parameters at the onset of labor Comparison of heart rate, systolic blood pressure (BP), diastolic BP, and saturation between Group RF and Group BF. It was found statistically not significant. VAS score before the epidural study drug was given, was 5 (4-5) in RF group, and was 5 (3-6) in BF group, and after 1 min, VAS score was 1 in both the groups thereafter. The score remained zero till at 100 min in both the groups till the time when the top-up dose was given. Bearing down reflex was present in all the patients as judged by the obstetrician. It was sluggish in 20% of patients in Group RF as compared to 10% in Group BF. Conclusions: From clinical and safety perspective, both RF and BF were reasonable choice for labor analgesia. Copyright:

INTRODUCTION

The pain of childbirth is conceivably the most severe pain many women will endure in their lifetime. Labor pain was rated to be as painful as a digit amputation without anesthesia[1] or second-degree burns to the skin.[23] Since pain relief in labor has always been surrounded with misconception and contention, so providing effective and safe analgesia during labor has always remained an ongoing challenge.

The parley over the appropriateness of anesthesia for labor[4] continued till 1853, until John Snow administered chloroform to Britain's Queen Victoria during the birth of her eighth child, Prince Leopold.[5]

According to the American Society of Anesthesiologists (ASA) physical status classes I and II, who requested, “Labor causes severe pain for several women. There is no other circumstance where it is considered acceptable for any individual to experience untreated severe pain, amenable to safe intervention, while under a physician's care.”[6]

However, the fact needs to be emphasized that most nonneuraxial methods do not provide complete pain relief, but they do allow a woman to cope with her labor pain.[7]

In 1950s, when neuraxial techniques were introduced for labor analgesia, it was considered as the gold standard and incomparable due to its proven efficacy and flexibility with maternal satisfaction for intrapartum labor analgesia.[8]

It is the only technique which provides analgesia in the first and second stage of labor where analgesia can be converted to anesthesia if an operative intervention becomes necessary such as fetal distress, hemorrhage, labor dystocia, fetal malpresentation, and multiple gestation.

Multiple randomized controlled trials comparing epidural analgesia with systemic opioids, nitrous oxide, or both have demonstrated lower maternal pain score and higher maternal satisfaction with neuraxial analgesia.[191011]

Bupivacaine and ropivacaine are conventionally used to provide efficient epidural analgesia in labor. The value of bupivacaine is restricted by the risks of motor blockade (associated with maternal dissatisfaction and increased instrumental deliveries) and cardiac toxicity. Ropivacaine has the advantage of more sensory and motor differential blockade as well as decreased risk of systemic toxicity. There have been clashing comparisons of ropivacaine and bupivacaine for labor analgesia. Studies have suggested that ropivacaine produces less motor block than bupivacaine, while others found the drugs to be indistinguishable. Diluted solutions of epidural local anesthetics combined with opioids may be used to minimize unwanted motor block.[121314]

We undertook this study with the aim to evaluate whether ropivacaine offers any significant advantage over bupivacaine in regard to obstetric outcome in our institutional practice and whether a changeover from bupivacaine to ropivacaine was warranted. This study compares the efficacy of ropivacaine and bupivacaine in regard to pain relief, motor block, labor characteristics, and neonatal outcome.

Objectives

This study was designed to compare the efficacy of ropivacaine with fentanyl and bupivacaine with fentanyl as intermittent bolus technique in epidural labor analgesia with respect to pain relief, motor block, mode of delivery – vaginal/cesarean delivery, neonatal outcome – Apgar score, and neonatal intensive care unit (NICU) admission.

MATERIAL AND METHODS

This is a prospective randomized comparative study conducted in 60 patients who attended department of obstetrics and gynecology. The study was approved by institutional (ethical) review board. Written consent for participation in the study was obtained before recruitment and procedure was explained. Detailed history of the patient was taken and routine investigations such as complete blood count and platelet count were done as per our hospital labor protocol.

American Society of Anesthesiologists (ASA) physical status classes I and II, who requested for epidural analgesia, who had term singleton pregnancy of 36–42 weeks in the vertex position, and who were in active labor with cervical dilatation 3–4 cm were included in the study.

Women who refused for labor analgesia, who had contraindications to epidural block such as coagulopathies, local sepsis, severe anemia, and fixed cardiac output states, who were unable to co-operate, who were defined by the obstetrician as high-risk pregnancies (severe preeclampsia, insulin-dependent diabetes, and preterm pregnancies), and who had drug sensitivity were excluded from the study.

Patients who fulfilled the inclusion criteria and who gave consent were randomly allocated to one of the two groups of 30 each, using a computer-generated table of random number from our community medicine department to receive epidural study drug. Five-Para Monitor was used for continuous monitoring of noninvasive blood pressure (BP), electrocardiography, respiratory rate, and oxygen saturation.

No participant was given any sedative premedication. Before placement of the epidural catheter, visual analog scale (VAS) score was noted with VAS: 0 = no pain and 10 = the worst imaginable pain along the baseline vitals (T0 or Timezero). An 18-gauge intravenous (i.v.) cannula was inserted and the patient was started on an infusion of Ringer's lactate solution. The patient was then positioned in the left lateral position or sitting position based on the anesthetists’ convenience. Under strict aseptic precautions, the best interlumbar space between L2 and L4 was identified and infiltrated with 2% lignocaine. The epidural space was located using loss-of-resistance syringe, and 20-gauge multiorifice epidural catheter was threaded through the needle into the epidural space. The catheter was positioned in the cephalad direction with a length of constant 4 cm inside epidural space. Once the catheter was satisfactorily sited, occlusive was dressing applied. The patient was turned supine with a pillow under her right buttock to provide left uterine displacement. A test dose of local anesthetic (2 mL of 2% lidocaine with adrenaline) was injected via the epidural catheter to rule out intravascular or intrathecal placement of catheter. Conservation of motor function was determined using the modified Bromage scale in both legs (0: No paralysis, full flexion of knees and feet, 1: Inability to raise the extended leg and ability to move knees and feet; 2: Inability to move knees but ability to move feet; 3: Inability to flex ankle joints, complete motor blockade of lower limbs). Maternal adverse effects during the procedure such as nausea, vomiting, pruritus, bradycardia, trembling, and hypotension were recorded. After 10 min of loading dose, the study drug was given. Whenever pain recurred (breakthrough pain, i.e., VAS ≥3), additional top-up dose (10 mL) of the study drug with 25 μg fentanyl was given.

After we gave the epidural dose, urinary catheterization was done in all patients and was removed before the delivery.

Epidural analgesia was continued throughout the second stage of labor. At any point of time during the study period, hypotension was defined as systolic BP <20% of the baseline BP and was treated with bolus of 6 mg ephedrine hydrochloride. Bradycardia was defined as heart rate less than 20% of the baseline and was treated with 0.6 mg atropine sulfate. Sensory blockade height was assessed by loss of sensation to pin prick (blunt head of a pin).

Time taken for the requirement of a top-up dose was recorded. Labor was managed according to our obstetric department's protocols, and mode of delivery (normal/instrumental/cesarean delivery) was noted. Bearing down reflex was assessed as “present, sluggish, or absent.” Fetal heart rate was continuously monitored. Neonatal assessment was performed by assessing the Apgar score at 1 and 5 min and NICU admission. Subjective assessment of analgesia was assessed as excellent, satisfactory, or not satisfactory.

Statistical analysis

Discrete categorical data were presented as n (%); continuous data were written as either in the form of its mean and standard deviation (SD) or in the form of its median and interquartile range, as per the requirement. The normality of quantitative data was checked by measures of Kolmogorov–Smirnov tests of normality. For normally distributed, t-test was applied for statistical analysis of two groups. For skewed data or ordered categorical data, nonparametric Mann–Whitney U-test was used for statistical analysis of two groups. For categorical data, comparisons were made by Pearson's Chi-square test or Fisher's exact test as appropriate (%). For time-related variables of scores, Wilcoxon signed-rank test was applied; for normally distributed data, ANOVA followed by post hoc multiple comparison test (Dunnet's t-test) was carried out. All the statistical tests were two-sided and were performed at a significance level of α = 0.05. Analysis was conducted using IBM SPSS Statistics Windows, Version 22.0. (IBM Corp: Armonk, NY, United States).

RESULTS

Both groups were comparable in terms of demographic data and obstetric parameters at the onset of labor [Table 1]. Comparison of parity between Group RF and Group BF was found statistically not significant (P = 0.438). The mean cervical dilatation ± SD in Group RF was 3.80 ± 0.664 cm and in Group BF was 3.60 ± 0.498 cm. This variable was not statistically significant (P = 0.192)[Table 2]. The distribution of level of epidural catheter placement 4 cm inside space, among both the groups, did not have any statistical significance (P = 0.158); the comparison of heart rate, systolic BP, diastolic BP, and saturation between Group RF and Group BF was found statistically not significant [Table 1]. VAS score before the epidural study drug was given was 5 (4–5) in RF group and was 5 (3–6) in BF group. Five minutes after the study, drug VAS reduced to 1 in both the groups with P = 0.805 which was nonsignificant; thereafter, the score remained zero till at 100 min in both the groups. First top-up dose was given at 128 ± 50.115 min and 108.19 ± 40.284 min in RF and BF groups, respectively, with P = 0.169 which was again nonsignificant [Table 3].

Table 1

Demographic characteristics of the patients and data of maternal and fetal hemodynamic parameters

	Ropivacaine fentanyl Gp	Bupivacaine fentanyl Gp	P
Demographic data
Age (years)	24.57±2.97	24.60±3.0	0.96 (NS)
Height (m)	1.53±0.30	1.52±0.38	0.69 (NS)
Weight (kg)	66.7±2.97	68.31±3.9	0.07 (NS)
BMI (kg/m2)	28.50±1.19	29.57±1.41	0.086 (NS)
Parity - Multi: Primi	14:16	13:17	0.43 (NS)
Maternal heart rate
Before analgesia	98.83±10.5	94.9±11.7	0.31 (NS)
15 min after injection	96.03±8.5	93.73±11.9	0.38 (NS)
30 min after injection	94.4±7.7	89.5±11.5	0.060 (NS)
Maternal systolic BP
Before analgesia	121.33±3.7	118.53±6.9	0.058 (NS)
15 min after injection	119.3±5.1	116±6.7	0.067 (NS)
30 min after injection	115.8±6.9	115.9±6.2	0.938 (NS)
Maternal diastolic BP
Before analgesia	78.9±5.2	76.3±6.64	0.101 (NS)
15 min after injection	78.9±7.14	75.67±6.1	0.065 (NS)
30 min after injection	76.20±6.3	75.60±5.0	0.68 (NS)
Fetal heart rate
Before analgesia	142.97±2.1	143±1.7	0.948 (NS)
15 min after injection	143.3±2.4	143.13±1.8	0.859 (NS)
30 min after injection	142.63±1.8	143.40±2.4	0.171 (NS)

NS=Nonsignificant, BMI=Body mass index, BP=Blood pressure, GP=Group

Table 2

Obstetric characteristics and data of obstetrical and neonatal outcomes

	Ropivacaine fentanyl Gp	Bupivacaine fentanyl Gp	P
Obstetric characteristics
Gestational weeks
Initial cervical dilatation	3.80±0.6	3.60±0.49	0.192
Duration of first stage	168.9±10.5	179.12±9.5	0.703
Duration of second stage	15.07±4.25	13.04±4.4	0.089
Duration of third stage	13.93±1.71	13.0±2.19	0.083 (NS)
Mode of delivery (%)
Normal vaginal	15 (30)	13 (43.3)
LSCS	1 (3.3)	4 (13.3)
Vaginal delivery with episiotomy	14 (14.67)	13 (43.3)
Apgar score (min) (%)
At 1	≤7 (90)	≤7 (80)	0.472 (NS)
	≥7 (10)	≥7 (20)
At 5	≥7 (100)	≥7 (100)

NS=Nonsignificant, LSCS=Lower segment Caesarean section full form has been addressed, Gp=Group

Table 3

Effectiveness of analgesics in both groups and assessment using visual analog scale (1-10)

	Ropivacaine fentanyl Gp	Bupivacaine fentanyl Gp	P
VAS
Before epidural injection	5 (4-5)	4 (3-6)	0.119
At 5 min	1 (1-1.25)	1 (1-2)	0.805
At 15 min	0	0	1.000
At 30 min	0	0	1.000
At 45 min	0	0	1.000
At 60 min	0	0	1.000
At 75 min	0	0	1.000
At 100 min	1	1	1.000
At 110 min	2	≥3 (first top up) 108.19±40.284	0.169
At 130 min	≥3 (first top up) 128.5±50.115	0
At 150 min	0	0	1.000
At 170 min	0	0	1.000
At 190 min	1	≥3 (second top up) 185.69±26.061	0.574
At 210 min	≥3 (second top up) 213.7±20.116	0
At 230 min	0	0	1.000
Maternal satisfaction (%)
Excellent	90	73.3	0.211
Satisfactory	10	23.3
Unsatisfactory	0	3.33

VAS=Visual analog scale, Gp=Group

Bearing down reflex was present in all the patients as judged by the obstetrician. It was sluggish in 20% of patients in Group RF as compared to 10% in Group BF. It was not possible to evaluate because of caesarean delivery in 3.3% of patients in Group RF and 13.3% of patients in Group BF. The difference between the groups was not statistically significant (P = 0.247).

There were more normal vaginal deliveries with episiotomy (ND [+episiotomy]) in Group RF (46.7%) compared to Group BF (43.3%). Vaginal deliveries without episiotomy (ND [−episiotomy]) were also more in Group RF (50%) compared to Group BF (43.3%). One patient in Group RF (3.3%) and four in Group BF (13.3%) had cesarean deliveries. The difference was not statistically significant (P = 0.372).

Stage I labour lasted 168±10.5, 179.12±9.5, Stage II labour lasted for 15.07±4.2, 13.04±4.4, and Stage III labour lasted for 13.93 ±1.71and 13.0 ±2.19 in Ropivacaine – fentanyl and Bupivacaine – fentanyl Group respectively; all were not significant with P = 0.703, 0.089, and 0.083, respectively, of Stage I, II, and III.

Subjective of assessment of analgesia was excellent in 90% of parturients in Group RF as compared to 73.3% of parturients in Group BF. It was satisfactory in 10% of parturients in Group RF as compared to 23.3% of parturients in Group BF and not satisfactory in 0% in Group RF as compared to 3.3% in Group BF. The difference between the groups was not statistically significant (P = 0.211).

Majority of parturients had modified Bromage scale 1 (no impairment). This variable was statistically not significant. The neonatal outcome was performed by assessing the Apgar score at 1 and 5 min and NICU admission. 90% of neonates born to parturients in Group RF and 80% in Group BF had Apgar scores at 1 min ≤7. Ten percent of neonates born to parturients in Group RF and 20% in Group BF had Apgar scores at 1 min ≥7. The difference was not statistically significant (P = 0.472). All the neonates born to parturients in either group had Apgar scores at 5 and no neonate was admitted in the NICU.

DISCUSSION

Effective pain relief during labor is essential to reduce maternal and perinatal morbidity, which arises due to pain-induced maternal sympathetic activation and to avoid unnecessary cesarean sections performed due to maternal anxiety. Walking epidural analgesia on labor reveals lower pain scores, leading to higher maternal satisfaction with better cardiovascular rand pulmonary physiology. A disproportionate doctor/patient ratio along with high equipment cost has made labor analgesia an unmet right of laboring women in developing countries.[15] Multiple randomized trials comparing epidural analgesia and systemic opioids, nitrous oxide, or both have demonstrated lower maternal pain scores and higher maternal satisfaction with neuraxial analgesia. In addition to their analgesic benefits, the physiological benefits of neuraxial analgesia for the mother and fetus are well documented: neuraxial analgesia has been shown to improve maternal cardiovascular and pulmonary physiology and the acid–base status of the fetus.[16]

Writer et al.[17] suggested that ropivacaine was associated with an increased risk of spontaneous vaginal delivery as compared with bupivacaine due to reduction in motor block. Halpern et al.[18] showed that the rate of motor block was more frequent in the bupivacaine group, but the incidence of spontaneous vaginal delivery was similar, regardless of whether ropivacaine or bupivacaine was used for labor analgesia. Ropivacaine is not so much as lipophilic; it causes lesser penetration of large myelinated nerve fibers, thus having a lesser propensity to cause motor blockade when used in lower concentration or dose.[19]

Adding an opioid to the solution exhibits a local unaesthetic-sparing action by reducing the EC50 of local anesthetic in a dose-dependent manner.[20] Chhetty et al.[21] found 0.2% ropivacaine with 2 μg.mL−1 fentanyl more effective than 0.125% ropivacaine. Harms et al.[22] found 0.125% as the most suitable concentration for bupivacaine for epidural analgesia in labor. Patkar et al.[23] favored the intermittent bolus technique because it resulted in lesser total drug consumption and incidence of breakthrough pain, thereby representing a more efficacious mode of drug delivery. Lee et al.[24] and Fernández-Guisasola et al.[20] compared bupivacaine with ropivacaine, which was marketed as a levo-enantiomer because ropivacaine has a better sensory-motor differentiation and less cardiotoxic potential[2024] compared to bupivacaine. Chhetty et al.[21] found 0.2% ropivacaine with 2 μg.mL−1 fentanyl more effective than 0.125% ropivacaine. Harms et al.[22] found 0.125% as the most suitable concentration for bupivacaine for epidural analgesia in labor, so in our study, we compared ropivacaine 0.2% with 50 μg fentanyl with bupivacaine 0.125% with 50 μg in fentanyl, 16 mL each intermittently with a bolus of 10 l when VAS ≥3.

Lee et al.[24] outlined that bupivacaine was associated with prolongation in the first stage of labor. This could result from higher concentrations of commenced analgesia with a 0.25% solution, which prompted motor block, leading to elongation of labor. As opposed to other comparative studies, using these local anesthetics in a range of 0.075%–0.125% found no differences in the durations of the first or second stages of labor which are similar to our results.[202526]

Patkar et al.[23] favored the intermittent bolus technique because it resulted in lesser total drug consumption and incidence of breakthrough pain, thereby representing a more efficacious mode of drug delivery, so we decided to compare 0.2% ropivacaine with fentanyl and 0.125% bupivacaine with fentanyl to see whether a less potent ropivacaine offers the same pain relief and if it offers any significant advantage over bupivacaine at these concentrations.

Afshan et al.[27] found that when the epidural catheter was to be kept for a longer period of time, then the length of the epidural catheter should be more than 3 cm. In our study, 4 cm length of epidural catheter inside the epidural space was kept constant in all cases, and this distribution of level of epidural catheter placement in both the groups did not have any statistical significance (P = 0.158).

In our study, we found that median (interquartile range) pain scores were 5 (4–5) and 4 (3–6) in RF and BF groups, respectively at T0. After 5 min of epidural dose, it came down to 1 (1–1.25) in RF group and 1 (1–2) in BF group. This study finding echoed in the study done by Paddalwar et al.,[28] when they compared ropivacaine 0.125% and bupivacaine 0.125%, both with fentanyl 2 μg.mL−1 Similar finding was noted by Fernández-Guisasola et al.[21] when they compared 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl. There were no clinically demonstrable differences in the onset of pain relief in both the groups. No statistically significant difference in pain was found.

Chhetty et al.[21] found excellent bearing down efforts (maternal expulsive efforts) in 80% parturients who received 0.2% ropivacaine with 2 μg.mL−1 fentanyl when they compared ropivacaine 0.125% with ropivacaine 0.2%, both with fentanyl as an adjuvant. In our study, it was sluggish in 20% of patients in Group RF as compared to 10% in Group BF though both the groups were comparable.

It is presumed that ropivacaine has a significant selectivity for sensory fibers than motor fibers, due to its lower lipophilic capacity compared with bupivacaine. Accordingly, it is less likely to cause motor blockade and neurotoxicity.[2930] There were no cases of motor blockade (modified Bromage scale 1) in either group in our study. This could be allied to the use of very low and titrated concentrations of a local anesthetic through the addition of opioids. It may also account for our high spontaneous vaginal delivery rate. Similar findings were also observed by Patkar et al.,[23] who used 0.1% ropivacaine with 0.0002% fentanyl, and Chhetty et al.,[21] who did a comparative study of ropivacaine 0.2% and 0.125%, with fentanyl. Paddalwar et al.,[29] who compared bupivacaine 0.125% and ropivacaine 0.125%, had observed Bromage grade 2 (mild) with bupivacaine 0.125% in 16% of patients only.

Halpern and Walsh[28] found no difference in spontaneous delivery or any other obstetric outcome between ropivacaine and bupivacaine when used in labor epidural analgesia. Our results were consistent with these studies, and there were high rate of spontaneous vaginal delivery and low rate (3.30% in Group RF and 13.3% in Group BF) of cesarean delivery. Both the groups were comparable.

The recent update of Cochrane review[31] which compared epidural analgesia with other forms of analgesia comprised of inhalational and i.v. (mainly opioids) observed that there were less fetal acidosis and less naloxone administration in babies born to mothers having labor epidural analgesia. The meta-analysis of Halpern and Walsh[28] also found no difference in neonatal outcomes between ropivacaine and bupivacaine when used in labor epidural analgesia. In our study, the fetal heart rate during labor was within normal limits. There was no incidence of postepidural fetal bradycardia. The median (interquartile range) for Apgar score at 1 min was 6 (6–7) in both the groups, and at 5 min, it was 9 (9–10) in both the groups. The difference was not statistically significant at 1 and 5 min. All neonates born to parturients in Group RF and in Group BF had Apgar scores at 5 min ≥7.

Halpern and Walsh[28] exhibited no difference in quality of analgesia or maternal satisfaction and provided excellent labor analgesia. In our study, 92% of parturients in Group RF and 73.3% of Group BF experienced excellent analgesia and difference was not statistically significant.

CONCLUSIONS

Both ropivacaine and bupivacaine provide equivalent labor analgesia with high maternal satisfaction. A combination with opioids was preferred as it has dose-lowering effect. No adverse obstetric or neonatal outcomes were observed in either of the groups. Therefore, either drug is a reasonable choice for labor analgesia and can be used without jeopardizing the safety of the mother and fetus.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.