Labor Epidural Analgesia: Comparison of Two Different Intermittent Bolus Regimes.

BACKGROUND: Optimal labor analgesia can be provided with epidural by addition of opioid to the local anesthetic. AIMS: The aim of this study is to compare the efficacy of labor epidural bolus regimes 20 mL of 0.1% ropivacaine with 40 μg fentanyl versus 15 mL of 0.1% ropivacaine with 15 μg fentanyl as epidural bolus dose. SETTINGS AND
DESIGN: This was prospective double-blinded randomized study.
MATERIALS AND METHODS: After approval from the Institutional Ethical Committee, 50 consenting parturients in active labor were allotted into two groups by closed envelope technique. Group A received 20 mL of 0.1% ropivacaine with 40 μg fentanyl, whereas Group B received 15 mL of 0.1% ropivacaine with 15 μg fentanyl as an epidural bolus dose. The onset, duration of analgesia, motor block, top-up doses required, consumption of ropivacaine, and fentanyl and fetomaternal outcome were compared. STATISTICAL ANALYSIS USED: Numerical variables are expressed as a mean and standard deviation and categorical variables are expressed as frequency and percentages. To obtain the association between categorical variables and different doses Fischer's exact test was applied. To compare clinical parameters between different drug doses independent two-sample t-test were applied. Mann-Whitney U-test applied for nonparametric data.
Results: Effective labor analgesia with no motor blockade was observed in both groups with no failure rate. Duration of analgesia was significantly longer in Group A (166.8 ± 54.64 vs. 100.2 ± 32.39 min P < 0.001). The onset of analgesia was faster in Group A (88% vs. 16% within 7 min, P < 0.001).
CONCLUSION: Labor epidural analgesia with larger volume boluses produces faster onset and prolonged duration of analgesia.

INTRODUCTION

The role of epidural in labor analgesia is universally accepted and practiced in many places. It can be provided with local anesthetic alone or in combination with opioids.[12345] Previous studies have shown that intermittent boluses are better than continuous infusion and provide better analgesia with the lesser requirement for rescue boluses.[6] In contrast, a study by Lange et al.[7] could not demonstrate that programmed high-rate epidural injections are superior to low-rate epidural injections. We hypothesized that a higher volume of intermittent epidural bolus dose would produce rapid onset and prolonged duration of analgesia than produced by lower volume regimen. Thus we aimed to compare the efficacy of larger volume of 20 mL of 0.1% ropivacaine with 40 μg fentanyl versus 15 ml of 0.1% ropivacaine with 15 μg fentanyl given as bolus for epidural labor analgesia. Primary outcome studied were the assessment of duration of adequate analgesia with each bolus. Secondary outcomes included the incidence and degree of maternal hypotension, motor blockade, pruritus, instrumental delivery, conversion to cesarean section, and fetal outcomes such as bradycardia, fetal acidosis, and Apgar score.

MATERIALS AND METHODS

After the approval of the Institutional Ethical Committee on 10/8/2016 and informed consent from patients, this prospective, double-blinded, randomized study was conducted in a teaching hospital from November 2016 to December 2017. Fifty parturients between 18 and 40 years belonging to the American Society of Anesthesiologists (ASA) physical status Classes I and II, with uncomplicated cephalic singleton pregnancy was recruited. Patients in active labor and desirous of having a labor epidural were randomly assigned to two equal groups by closed envelope technique [Figure 1]. Exclusion criteria included hypersensitivity to study drugs, bleeding disorders, decreased platelet counts, sepsis, spinal column deformities, and history of spine surgery.

Figure 1

Consort flow diagram

All the parturient enrolled in the study had assessment of pain using visual analog scale (VAS) before placement of the epidural catheter. After attaching monitors and starting an intravenous line, 500 mL of Ringer lactate was infused. The patient was placed in left lateral position and an epidural catheter was placed by consultant anesthetist at L3–L4 interspace under aseptic precautions using Portex Epidural minipack system 2 (manufacturer: Smiths Medical, Czech Republic). Test dose was avoided in all our patients. Accidental intrathecal or intravascular placement of catheter was ruled out by aspiration of the multi-orifice catheter. If there was an accidental intrathecal or intravascular placement, the catheter was re-sited, and the patient was removed from the study. The study drug was injected as incremental boluses. Group A received 20 mL of 0.1% ropivacaine with 40 μg fentanyl, whereas Group B received 15 mL of 0.1% ropivacaine with 15 μg fentanyl as an initial bolus dose and the time was noted. Same dose regimen was used as subsequent top-up dose on patients demand for pain relief. A second anesthetist who was blinded to the technique assessed the adequacy of analgesia. Analgesia was considered adequate if the pain score was <3. The onset of analgesia was defined from time of first bolus dose to time of achieving visual analog score <3. If adequate analgesia was not achieved even after 15 min, an additional 10 mL of medication was administered, and analgesia reassessed. If pain relief was inadequate 15 min after the additional dose of ropivacaine; the epidural anesthetic was considered as epidural failure, and patient was withdrawn from the study. Duration of analgesia was defined as the time from first bolus dose to the time for request for the second bolus dose. The presence of motor block in the lower extremities was assessed using a Breen modified Bromage scale (Grade 1 as complete motor block to Grade 6 as no motor block). Hypotension was defined as mean arterial blood pressure of <20% from baseline and was treated with bolus of 6 mg intravenous ephedrine. Bradycardia was defined as heart rate <50 bpm. and was treated with bolus doses of 0.3 mg atropine sulfate. Demographic data (age, weight, height), obstetric data (parity, dilatation of the cervix [0–10 cm], station of the vertex of the presenting part [−3 to +3], effacement of the cervix (%), membrane status was noted prior to the initiation of labor analgesia. Pain score (VAS), motor block characteristics and vital parameters (pulse, systolic-diastolic, and mean arterial pressure) were recorded at 0 (before epidural), 10 min and then every 30 min until the delivery. Labor was managed according to obstetric protocol and mode of delivery was noted. Fetal heart rate monitoring was done by continuous cardiotocograph. Neonatal assessment was done by Apgar score at 0 and 5 min and by fetal arterial blood gas.

Statistical analysis

All statistical analysis was performed with IBM SPSS 20.0 (SPSS Inc., Chicago, IL, USA). Numerical variables are expressed as mean and standard deviation and categorical variables are expressed as frequency and percentages. To obtain the association between categorical variables and different doses, Fischer's exact test was applied. To obtain the comparison of clinical parameters between different drug doses independent two-sample t-test were applied. Mann–Whitney U-test applied for nonparametric data.

Sample size

Based on the pilot study, duration of analgesia with 99% confidence interval and 90% power, the minimum sample size came to 10 per each group, but we have assigned 25 parturients in each group.

RESULTS

Patients in both groups were similar with respect to demographics, ASA distribution, parity and other obstetric data [Table 1]. Effective labor analgesia with no motor blockade was observed in both groups with no failure rate. Duration of analgesia after initial bolus dose was significantly longer in Group A than B (166.8 ± 54.64 vs. 100.2 ± 32.39 min P < 0.001) [Table 2]. Mean VAS scores at 10, 30, 60, 90, and 120 min following initial bolus was comparable between both groups, P > 0.05 [Figure 2]. The requirement of top-up doses was significantly less in Group A compared to B (1.48 ± 0.59 vs. 2.12 ± 1.01, P = 0.009). Consumption of ropivacaine was comparable in both groups but consumption of fentanyl was significantly higher in Group A than Group B (59.2 ± 23.44 vs. 42.4 ± 20.26, P = 0.009). Onset of analgesia was faster in Group A than B (88% vs. 16% within 7 min, P < 0.001) 28.0% patients in Group A delivered by lower segment caesarean section (LSCS), 4.0% by vacuum assistance and 68.0% by normal delivery in comparison to 44.0% LSCS and 56.0% normal delivery in Group B which is statistically comparable, P = 0.336. About 16.0% of patients in Group A and 8% in Group B complained of pruritus and 8.0% in Group A and 4% in Group B complained of nausea, which is statistically insignificant, P = 0.543. There was no significant change in hemodynamics in both the groups. There was statistically significant decrease in 1 min Apgar score in Group A as compared to Group B (7.68 ± 0.69 vs. 8.0 ± 0.00, P = 0.029), but there was no significant change in 5 min Apgar between Group A and B (9.0 ± 2.89 vs. 9.0 ± 2.77, P = 0.322). There was statistically significant decrease in pH in Group A compared to Group B (7.264 ± 0.0699 vs. 7.31 ± 0.0577, P = 0.008) [Table 3].

Table 1

Demographic and obstetric data

Table 2

Dose requirement, onset, block characteristics

Figure 2

Comparison of pain scores

Table 3

Maternal and fetal effects

DISCUSSION

In our study, effective labor analgesia with no motor blockade was observed in both groups with no failure rate. Primary outcome studied was the assessment of duration of adequate analgesia with each bolus. Prolonged duration of analgesia achieved by Group A could be attributed to the larger volume of local anesthetic as well as a higher dose of fentanyl used. Longer duration of analgesia decreases the anesthetic workload in a busy labor room. It can also improve maternal satisfaction by reducing breakthrough pain.[8] Even though Group A received larger volume of local anesthetic, number of top-up boluses required was less. Hence, ropivacaine consumption was comparable between the groups. However, the fentanyl consumption in Group A was significantly higher than in Group B.

Ropivacaine is known to be associated with reduced systemic toxicity and motor blockade than bupivacaine, allowing the parturient to be ambulant.[9] Hence, it is preferred for providing labor analgesia. The minimum concentration of 0.2% ropivacaine is required to produce adequate labor analgesia.[10] However, the addition of opioids to local anesthetics allows lower concentration of local anesthetic to produce similar quality of analgesia.[11] Use of lower concentration of local anesthetic results in the lesser motor blockade, thereby reducing instrumental deliveries.[1213] In a meta-analysis by Writer et al. use of ropivacaine compared to bupivacaine resulted in lesser instrumental and cesarean deliveries.[14] Hence in our study, we have added fentanyl to ropivacaine in both the groups. Addition of fentanyl 2 μg/mL to 0.1% ropivacaine is shown to produce analgesia equivalent to 0.2% ropivacaine.[1] Studies have shown that infusion 0.05% of ropivacaine and bupivacaine with fentanyl 1.5 μg/mL provided good and safe labor analgesia.[15] The side effects commonly associated with ropivacaine are bradycardia, hypotension, paresthesia and urinary retention. We did not encounter any of these complications in both the groups. Epidural boluses did not produce any significant hemodynamic changes in both groups. Patients in both groups did not require any ephedrine or atropine. Delivery by cesarean or normal delivery was comparable between the two groups. In this study, no motor block was observed in both groups. Meta-analysis comparing epidural analgesia produced by bupivacaine with fentanyl versus ropivacaine with fentanyl showed the significantly lower incidence of the motor block when ropivacaine was used.[16] Motor block is known to occur if bupivacaine or higher concentration of ropivacaine are used.[17] However in contrast Beilin and Halpern[18] in their review comparing ropivacaine and bupivacaine for labor analgesia did not find any added advantage in the routine use of ropivacaine for labor analgesia.

The onset of analgesia was faster in Group A. This could be because of the larger volume of local anesthetic and higher dose of fentanyl used. The higher volume of the epidural bolus produces higher injection pressure which improves drug distribution in the epidural space providing better and rapid onset of analgesia.[81920] Chhetty et al.,[2] compared the efficacy of 15 mL of 0.125% and 0.2% ropivacaine with 2 μg/mL fentanyl and found latter to be superior regarding faster onset, prolonged duration and consumption of opioids.

Intermittent bolus dosing of labor epidural is known to reduce the local anesthetic consumption, decrease surgical delivery, and improved maternal satisfaction compared to continuous epidural infusion.[21] Studies have shown that intermittent epidural boluses have resulted in lower incidence of motor block and instrumental delivery.[2223] In Group A, though the number of boluses required was less, the amount of fentanyl consumption was higher. Fentanyl 2 μg/mL was used previously in some similar studies.[24] The prolonged analgesia observed in Group A could be attributed to this higher dose of fentanyl used. The side effects associated with opioids are nausea, pruritis, respiratory depression, and lower Apgar scores in the neonate. In spite of the increased consumption of opioids in Group A, the incidence of pruritis and nausea and vomiting was not significantly different between the two groups. No parturient had hypersensitivity reaction, urinary retention or respiratory depression. There was a statistical difference in Apgar score at 1 min. However, this difference of (7.68 vs. 8) is not clinically significant. There was a statistically significant decrease in pH in Group A (7.264 vs. 7.31), but this difference was also not of any clinical significance. The Apgar score at 5 min was comparable between the two groups. All the babies faired well and none of the babies in both Group required neonatal intensive care or ventilation.

Limitations of the study

We could have used the same concentration of fentanyl in both groups so that the comparison of the effect of volume could be understood better. The effect of boluses according to the stage of labor could have been studied. We did not discriminate parity which has an effect on labor pain while recruiting patients. A larger sample size could have provided a wider perspective on maternal and fetal effects.

Future perspective

A study comparing the large volume of dilute local anesthetic with 1, 1.5 and 2 μg/mL of fentanyl could be done on a larger population to find the lowest dose of fentanyl required to produce adequate and safe labor analgesia.

CONCLUSION

Though both the concentrations were effective in producing labor analgesia, use of larger volume produces faster onset and prolonged duration of analgesia with less requirement for top-up boluses.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.