Comparative Efficacy of Minimal Concentration of Racemic Bupivacaine (0.0625%) with Fentanyl and Ropivacaine (0.1%) with Fentanyl for Epidural Labor Analgesia.

BACKGROUND AND AIMS: This study aims to compare the minimum effective concentration of local anesthetic (LA) bupivacaine and ropivacaine with highly lipid soluble opioids fentanyl for providing optimal labor epidural analgesia. SETTINGS AND
DESIGN: The objective of this study was to evaluate the efficacy of racemic bupivacaine 0.0625% and 0.1% of ropivacaine both mixed with 2 μg/ml of fentanyl for epidural labor analgesia in parturients with spontaneous labor and normal fetal heart rate tracing.
METHODOLOGY: Sixty parturients requesting for labor analgesia were divided into two groups. Group B (n = 30) received racemic bupivacaine (0.0625%) and fentanyl 2 μg/ml of 10 ml and Group R (n = 30) received ropivacaine (0.1%) and fentanyl 2 μg/ml. In both groups, the drug was given in 5 ml fractionated doses at 5 min interval. Parturients not experiencing analgesia within 15 min of initial bolus were supplemented with additional 5 ml of the same concentration of the solution. Epidural analgesia was maintained by timed top ups at the end of 90 min with the dosage equal to the initial dose of the drug. Duration of labor analgesia, motor block, visual analog scale, maternal hemodynamic parameters, mode of delivery, and maternal satisfaction was assessed. STATISTICAL ANALYSIS: Data were analyzed with odds variance, unpaired t-test, and Chi-square tests. P < 0.05 was considered statistically significant.
RESULTS: In our study, results indicate that both drugs were equally effective clinically. Maternal demographic characteristics were comparable. There were no statistically significant differences in visual analog pain score, highest sensory block, maternal satisfaction, mode of delivery, total dose of LAs during labor and motor block at delivery between the groups.
CONCLUSIONS: In our study, both the drugs produced equivalent analgesia for labor at low concentration when used with highly lipid soluble opioid such as fentanyl.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Labor pain is excruciating and a significant contributor of stress and anxiety. Painful uterine contractions cause maternal hyperventilation and increased catecholamine release resulting in maternal and fetal hypoxemia.[1] Providing labor analgesia takes away the disadvantage and result in better maternal and fetal outcome. An ideal labor analgesic technique should provide adequate and satisfactory analgesia without any motor blockade or adverse maternal and fetal effects. Among the variety of labor analgesia techniques, epidural analgesia remains gold standard for providing pain relief during labor.[23] Even though combined spinal epidural analgesia (CSEA) is considered as a safe technique with greater maternal satisfaction, there were no differences in maternal satisfaction, mode of delivery, and ability to ambulate between CSEA and epidural techniques.[45]

With the emerging concept of low dose and minimal local anesthetic (LA) dose and volumes, all present day labor epidurals are low-dose epidurals. In the last decade, the concentration of LA used to maintain labor epidural analgesia has been decreasing (0.0625%–0.125%) in an attempt to reduce the total dose of LA used as well as to avoid motor blockade.[67]

Epidural bupivacaine provides excellent sensory block and has been used for labor analgesia for many years. However, concern about its cardiac toxicity and the intensity of motor block has led to the investigation of other agents. Ropivacaine has been associated with reduced incidence of operative vaginal delivery and less motor block when compared to bupivacaine.[8] Recently, it has been shown that ropivacaine appears equipotent to bupivacaine, less cardiotoxic and neurotoxic and seem to be more suitable agent for pain relief in laboring women.[910]

In the randomized study comparing levobupivacaine, ropivacaine and bupivacaine with fentanyl for labor analgesia concluded that all three regimens were effective during the first stage of labor although pain scores were higher in those receiving levobupivacaine. Motor block was greater with bupivacaine than with levobupivacaine.[11]

The quality of analgesia is excellent when highly lipid-soluble opioids are added. The addition of opioids to LA reduces its requirement by synergistic effect of opioid receptors in the spinal cord. This reduces the chances of motor blockade and the hemodynamic perturbations.[12]

METHODOLOGY

After obtaining clearance from the Institutional Ethical Committee, a prospective randomized double-blinded study was conducted on sixty parturients with singleton term pregnancy with physical status American Society of Anesthesiologists Classes I and II in spontaneous labor with normal fetal heart rate tracing, who requested for labor analgesia.

Parturients with medical disorders, obstetric complications, fetal malpresentations, and those with contraindication for regional analgesia were excluded from the study. After obtaining informed written consent, parturient was randomly allocated by a computer-generated table of random numbers by a person blinded to the procedure to avoid selection bias into two groups of thirty each as Group bupivacaine (B) (n = 30) and Group ropivacaine (R) (n = 30).

Double-blinded randomization to epidural analgesia procedure was accomplished by means of a computer-generated randomization list. The procedure was carried out by one anesthesiologist while the observations were made by the second one who was not present at the time of the procedure. The progress of labor and other obstetric parameters and fetal heart rate (FHR) were assessed by an obstetrician who was also blinded to the group allocations.

Before the institution of analgesia, parturients were administered 500 ml of Ringer's lactate solution, monitors connected (electrocardiogram [ECG], SpO2, noninvasive blood pressure [NIBP]), and baseline readings were noted. Parturients were placed in the left lateral position, and with all the aseptic measures, epidural space was identified by a midline approach at L3–L4 level with 18-gauge Tuohy needle using loss of resistance to saline technique. After negative aspiration for blood and CSF, the epidural catheter was threaded on through the Tuohy needle, and the needle was carefully withdrawn over catheter adjusting the catheter length of 3–4 cm inside the space.

Once the epidural catheter's position in the epidural space was confirmed, 10 ml of study drug of either 0.0625% bupivacaine with fentanyl 2 μg/ml or 0.1% ropivacaine with fentanyl 2 μg/ml was given in 5 ml fractionated doses with 5 min interval.

All the parturients in the both groups were familiarized with a visual analog scale (VAS) (0 = no pain, 10 = worst pain imagined). Parturients not experiencing analgesia (VAS >4) within 15 min of initial bolus were supplemented with additional 5 ml of solution. At the end of 30 min, if parturient does not experience pain relief, they were excluded from the study.

The SpO2, heart rate, NIBP, FHR were monitored before the insertion of catheter and at intervals of 5, 10, 20, 30, 45, 60, min and every 30 min until delivery.

Analgesia was maintained by timed top ups at the end of 90 min whether the parturient had pain or not, without breakthrough pain experiences. The dosage of top ups was equal to the initial dose of the drug. Adverse effects such as hypotension, arterial desaturation, ECG abnormalities, pruritis, and nausea were noted and managed if necessary.

A fall of systolic blood pressure >20% from the baseline or <90 mmHg reading was taken as hypotension. Hypotension was managed by O2 supplementation, left uterine displacement, intravascular volume expansion, and intravenous bolus ephedrine 3 mg as required.

After the administration of bolus dose of drug and also after giving timed top ups following parameters were noted: FHR, cervical dilatation, pain score (VAS), highest level of sensory block (assessed by loss of temperature discrimination to alcohol swab), motor block (intensity as per Bromage scale), total dose of LA consumed per hour and number of additional supplemental doses administered. All the parameters were assessed at 20 min after the initial bolus dose and every 30 min thereafter. The mode of delivery (spontaneous vaginal, instrumental vaginal, and cesarean section) was also noted. After the delivery, maternal satisfaction levels with epidural analgesia (on a numerical scale 0 = totally unsatisfied, 10 = totally satisfied) were noted.

Statistical analysis

Data were analyzed using software version SPSS-20 (IBM SPSS statistics for windows, version 20.0. Armonk, NY, USA). Demographic data were analyzed using analysis odds variance. Unpaired t-test and Chi-square tests were used wherever appropriate. Standard tests of significance were applied to determine “P” values, P < 0.05 was considered statistically significant. Trend graphs and bar graphs were drawn accordingly.

RESULTS

Demographic profile

Maternal demographic characteristics such as age, height, and weight were comparable in both groups.

Mode of delivery

Mode of delivery data [Table 1 and Figure 1] suggests no significant difference between two groups regarding the incidence of spontaneous, instrumental, and cesarean delivery.

Table 1

Mode of delivery

Figure 1

Mode of delivery

Highest level of sensory blockade

As the level of sensory block achieved in each parturient varies, the dermatomal level achieved is taken as a non-numerical variable. The most frequent value (mode) achieved in percentage was considered in all the sixty patients and also separately in Group B and Group R [Table 2 and Figure 2].

Table 2

Sensory level of analgesia

Figure 2

Level of sensory block

Duration of labor

The mean duration of epidural analgesia [Table 3 and Figure 3] was 220 ± 55.34 min for Group B and 209 ± 75.35 for Group R (P > 0.522).

Table 3

Mean duration of analgesia

Figure 3

Duration of labor

Motor blockade

In Group B 13 (43.3%) and in Group R 14 (46.7%) experienced Grade 1 motor block (assessed by Bromage scale) [Table 4 and Figure 4].

Table 4

Motor blockade

Figure 4

Total dose of local anaesthetic used

Visual analog scores

Our results were expressed as trend of mean VAS score in all thirty patients of each group at 0, 5, 10, 20, 30, 45, and 60 min and every 30 min after that until delivery [Figure 5]. Before epidural injection, the mean score was 6.69 and 7.30 in Group B and Group R, respectively. After administering the drug, the mean VAS in Group B was 2.577 ± 0.63 and in Group R was 2.417 ± 0.63 which were statistically not significant (P > 0.05) between the groups. The onset of analgesia was greatest at 20 min and similar between groups. There were few episodes of breakthrough pain at 180, 270, and 300 min but VAS scores were <4. This was probably because of top up of low concentration of LA solution at regular intermittent intervals (90 min) and not as a continuous infusion.

Figure 5

Visual analogue pain scores

Hemodynamic parameters

We found no significant alterations with respect to maternal vital parameters SpO2, pulse rate, and FHR between two groups. There were no clinically significant adverse effects such as hypotension, bradycardia, and arterial desaturation in both groups requiring active intervention.

Maternal satisfaction

The maternal satisfaction was assessed based on subjective assessment and categorized as excellent, good, satisfactory, and poor. 33.3% of Group B had excellent results, 50% had good results, and 16.66% had satisfactory results. In Group R, 20% had excellent, 53.33% had good, and 26.66% had satisfactory results [Table 5 and Figure 6].

Table 5

Maternal satisfaction

Figure 6

Patient satisfaction

DISCUSSION

In the last couple of years, many attempts were made to provide labor analgesia by newer lower concentration of drugs with highly lipid soluble opioids such as fentanyl to reduce systemic toxicity and to preserve the motor function during the process of normal labor.[13]

There have been few debates regarding the minimum LA concentration of ropivacaine for starting of epidural labor analgesia. Polley et al.[14] and Palm et al.[15] stated that ropivacaine in at 0.01% showed less potency. On the contrary, Owen et al.[16] showed that fentanyl 2 μg/ml when added to 0.1% ropivacaine the analgesia was improved to a quality almost equal to 0.2% ropivacaine. In our study, we found that 0.0625% of bupivacaine with 2 μg/ml of fentanyl and 0.1% of ropivacaine with 2 μg/ml of fentanyl given in 5 ml fractionated doses with 5 min interval produced effective labor analgesia. We found no differences in the highest level of sensory block in both groups. Similar observations have been reported in other studies where no differences were found in the maximum height of the block with 0.5% and 0.75% concentrations of each drug.[17] However, use of these two drugs in low doses with opioids as in our study, have not been much reported.

In our study, we found that 0.0625% of bupivacaine with 2 μg/ml fentanyl and 0.1% of ropivacaine with 2 μg/ml of fentanyl given in 5 ml fractionated doses given for lumbar epidural labor analgesia produced effective labor analgesia with a mean duration of analgesia in Group B of 220 ± 55.3 min and in Group R of 209 ± 75.35 min (P > 0.522).

There was no difference in motor blockade between the two Groups B and R. Most of our patients had a Bromage score of 0 or 1. We decided to test whether this statistically insignificant value had any clinical significance because we considered the most frequent Bromage score reached in all patients in both groups of our study, which holds good with a study comparing 0.5% bupivacaine and 0.75% ropivacaine which also showed no significant differences in motor block[17] and Scott et al.,[18] McCrae et al.,[19] Owen et al.[20] studies showed that motor block was similar in bupivacaine and ropivacaine groups. In contrary, other studies shows that ropivacaine produces less motor blockade with shorter duration of action as compared to bupivacaine at higher concentrations.[1721] Also in a meta-analysis,[15] the incidence of motor block was found to be more frequent in the bupivacaine group in 19 of 23 studies. As our study used lower concentration of bupivacaine (0.0625%) than that of ropivacaine (0.1%) with fentanyl of 2 μg/ml, the difference in motor block was not statistically significant.

The quality and intensity of analgesia in our study were assessed by VAS score. Similar pain scores in bupivacaine and ropivacaine group in the first stage and second stage of labor suggested identical good quality of analgesia. Our results were expressed as a trend of mean score VAS in all the thirty patients of each group at 0, 5, 10, 20, 30, 45, and 60 min and 30 min thereafter until delivery. Before epidural injection the mean score 6.69 and 7.30 in Group B and Group R, respectively and after administrating the drugs, the mean VAS in Group B was 2.577 ± 0.63 and Group R 2.417 ± 0.63 (P = 0.95) which was statistically insignificant between the groups. Campbell et al.[15] also observed that the mean duration of analgesia was not statistically different between the groups.

We found no statistically significant differences with respect to the occurrence of instrumental delivery and cesarean section between the two groups. Eddleston et al.[22] in their study and Halpern and Walsh[16] in a meta-analysis found that there was no statistically significant difference on the incidence of vaginal delivery and mode of delivery. Writer et al.[23] reported in a prospective meta-analysis that instrumental vaginal delivery was less frequent in women who received ropivacaine (0.25%) compared with those who received bupivacaine (0.25%).

Our findings in the study showed that total consumption of volume of drug in ropivacaine – fentanyl group was more with a mean of 24.46 ± 7.53 ml as compared to bupivacaine – fentanyl group with a mean of 21.88 ± 8.70 ml although the difference was statistically insignificant. Writer et al.[23] Campbell et al.[24] also found that hourly drug requirement and total drug requirement were similar for bupivacaine and ropivacaine in labor analgesia. Hoffmann-Kiefer et al.[25] observed that the mean total consumption was significantly more in ropivacaine group as compared to bupivacaine group.

No statistical significance was observed for the mean duration of labor which was in Group B 220 ± 55.34 min and Group R 209 ± 75.35 min (P = 0.522) which was comparable with that of Owen et al.[26] study.

Maternal satisfaction was assessed on the basis of patient perception. We found excellent grade 33% in Group B and 20% in Group R, good grade 50% in Group B and 53% in Group R, and satisfactory grade in 16.66% in Group B and 26.66% in Group R. The difference between groups in the grades was statistically insignificant.

No toxic effects were observed in our study as we had used very dilute concentration of bupivacaine for labor analgesia (0.0625%). Scott et al.[19] found that the onset of central nervous system symptoms occurred at lower dose of bupivacaine (99 mg) compared to ropivacaine (124 mg). In our study, no significant variations occurred with respect to maternal vital parameters, SpO2, and FHR between two groups requiring active intervention.

CONCLUSIONS

We conclude that bupivacaine 0.625% with 2 μg/ml of fentanyl and ropivacaine 0.1% with 2 μg/ml of fentanyl epidurally produce adequate and equivalent analgesia for labor and are well tolerated. There is no statistically significant difference in the pain scores, sensory level, motor block, labor duration, mode of delivery, amount of LA consumed, side effects, and maternal satisfaction between the two groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.