Dose of Local Anesthetic
The specific regimens and local anesthetic concentrations are listed in Table 1. Of the 9 included studies, 3 published data regarding the total dose of local anesthetic per hour during the study period.23,24,28 Five other studies20,22,25–27 reported the total dose given. The study of Chua et al.21 was not included in this analysis because the study concluded with the first need for anesthetic intervention. With these 8 studies (n = 652) there was a statistically significant reduction in total local anesthetic delivered with IEB (MD, −1.2 mg bupivacaine equivalents per hour; 95% CI, −2.2 and −0.3; I2 = 83%; Fig. 7A). Salim et al.26 used a concentrated local anesthetic mixture for their IEB group, different from their CEI group; therefore, we performed a sensitivity analysis excluding this study. The effect was smaller but still statistically significant in favor of IEB with less heterogeneity (MD, −0.7 mg/h; 95% CI, −1.2 to −0.2; I2 = 40%; Fig. 7B). There was no publication bias for local anesthetic consumption (P = 0.26).
Overall maternal satisfaction with labor analgesia was reported in 5 of the included studies.23–25,27,28 Four studies reported maternal satisfaction with a verbal rating scale (VRS) where 0 is very dissatisfied and 100 is extremely satisfied.23–25,27 Wong et al.28 reported maternal satisfaction with a 100-mm visual analog scale (VAS) score. Pooled data from the 5 studies showed greater maternal satisfaction in the IEB groups (MD, 7.0 mm; 95% CI, 6.2–7.8; Fig. 8). Exclusion of the study by Wong et al.28 did not have a significant effect on the pooled results (MD, 7.1 mm; 95% CI, 5.0–9.2). There was no publication bias for maternal satisfaction (P = 0.84).
Subgroup Analysis of Primary Outcomes
Each of the primary outcomes had a subgroup analysis completed based on: (1) the use of a combined spinal–epidural (CSE) technique to initiate labor analgesia and (2) the use of PCEA during maintenance of labor analgesia. Five studies initiated analgesia with a CSE.21,23–25,27 The initiation of labor analgesia with a CSE did not have a significant effect on any of the primary outcomes. The use of PCEA for maintenance of labor analgesia made a noteworthy effect on the duration of the first stage of labor and the total duration of labor. When PCEA was used for maintenance of labor, the duration of first stage was longer with IEB23,26,27 (MD, 20 minutes; 95% CI, −22 to 61). However, when PCEA was not used for maintenance of labor, the duration of first stage was shorter with IEB22,24 (MD, −61 minutes; 95% CI, −129 to 6; Fig. 9). The total duration of labor was reduced with IEB when PCEA was not used22,24,25 (MD, −86 minutes; 95% CI, −146 to −27), but not when it was used20,23,26–28 (MD, −4 minutes; 95% CI, −26 to 17; Fig. 4A).
Other than dose of local anesthetic, most of the secondary outcomes were infrequently reported. A meta-analysis was completed on specific outcomes that contained data from more than 1 study. There were no significant differences between the groups with respect to these outcomes. The results are summarized in Table 3.
Umbilical pH values and 1-minute Apgar scores were only reported in 1 study (no significant difference).22 The 5-minute Apgar was reported in 4 studies,22–25 in which the MD was −0.04 with a 95% CI of −0.2 to 0.1. The degree of sensory block was quantified in 4 studies. Leo et al.23 and Lim et al.24 reported the sensory block level at the first request for additional analgesia. Chua et al.21 reported the maximal sensory block level within the first 3 hours of analgesia, while Sia et al.27 reported the maximal sensory block during the entire study period. Within these studies, there was no significant difference between CEI and IEB with respect to sensory blockade. Capogna et al.20 designed their study to detect a clinically significant degree of motor blockade measured with the Bromage score modified by Breen et al.41 In their study, the incidence of motor block (defined as modified Bromage score 41 <6, i.e., the inability to stand and complete a partial knee bend) at least once during labor was significantly increased in the CEI group compared with the IEB group (26/70 vs 2/75, P < 0.001). Assuming the modified Bromage score <620 is equivalent to a traditional Bromage score >1,21,27,28 then the pooled results are not statistically significant (Table 3).
Nine high-quality low risk of bias RCTs have evaluated IEB versus CEI in laboring women. In healthy women requesting labor epidural analgesia, the mode of maintenance of epidural analgesia may not affect the mode of delivery. However, intermittent bolus dosing of local anesthetic may be associated with reduced local anesthetic consumption, decreased anesthetic interventions, and an improvement in maternal satisfaction when compared with those women receiving CEI. The 2 techniques of local anesthesia delivery appear to be comparable in terms of total duration of labor, but there was a statistically significant reduction in the length of the second stage of labor with IEB. The duration of the second stage was a much as 22 minutes shorter with IEB. Arguably, this may enter the realm of clinically significant, and IEB may positively affect labor progression. Although there was no statistically significant difference between the 2 groups with regard to the incidence of adverse events (Table 3), the wide CIs of the pooled results preclude us from making any conclusions.
Despite not reaching statistical significance, several outcomes should be considered potentially clinically significant. The pooled results for instrumental delivery rate, rate of anesthetic interventions, and duration of labor each have wide CIs that contain clinically significant end points, therefore precluding us from drawing conclusions from the pooled data for those outcomes. For instance the lower end CI for the OR for instrumental delivery is 0.35, a clinically significant possibility with IEB. With a heterogeneity measure of zero, 8 studies contributing to a very close statistical significance (P = 0.05) and an absolute risk difference of 5.2% suggest a number-needed-to-treat of 20 to prevent 1 instrumental delivery. The effect size of 0.59 suggests that future trials of IEB should include approximately 486 participants (G-Power v 3.0 2006, Mannheim, Germany) to show a statistically significant reduction in the instrumental delivery rate compared with standard CEI.42 Induced versus spontaneous labor is a potential factor in these important outcomes; however, not all studies restricted the inclusion criteria nor specifically reported this event; therefore, a subgroup analysis was not possible.
Interference with normal labor progression leading to instrumental deliveries is a potentially unfavorable outcome of labor analgesia. However, modern labor analgesia with low concentrations of local anesthetics can be administered without adversely affecting labor outcomes.42 In the Comparative Obstetric Mobile Epidural Trial (COMET) conducted in the United Kingdom, Wilson et al.43 demonstrated that despite improved analgesia and lower doses of local anesthetic in the CSE analgesia arm of the study, this technique did not alter delivery modality or duration of labor. Despite the lack of statistical significance to alter labor outcomes with IEB delivery of epidural analgesia, the improvement in maternal satisfaction, which may loosely reflect improved analgesia, is still an important goal for labor analgesia research.
Satisfaction with labor analgesia is an important outcome of the quality of care given to women. It is a complex measure commonly used to describe overall adequacy of pain relief. However, maternal satisfaction involves many factors—maternal involvement in decision making, perception of emotional control, maternal expectations, and labor pain.44–46 Furthermore, labor pain is more than a simple physiological process; it is a complex reaction for which inadequately validated measures of maternal satisfaction, such as VAS and VRS measures, may or may not necessarily correlate to the effectiveness of pain relief.47,48 Given the complexity of measuring satisfaction, the different scales used, and the timing of such a measure, the lack of heterogeneity (I2 = 0%) should be interpreted with caution.
All of the studies had small sample sizes reflecting the difference in the outcomes they were powered to detect. Two trials were powered to detect a difference in the dose of local anesthetic delivered.27,28 A single study was powered to detect a difference in the duration of labor.26 Fettes et al.22 powered their study to detect a difference in VAS score at an arbitrary time, 4 hours after the intervention. Four studies were powered to detect a difference in need for anesthesia interventions.21,23–25 Other than Capogna et al.,20 none of the included trials was powered to detect a difference in the side effects of labor analgesia. No studies were powered to detect a difference in maternal satisfaction.
Capogna et al.20 published the largest and most recent trial, which was powered to detect a difference in the incidence of motor blockade (primary outcome) and instrumental deliveries (secondary outcome). They reported a greater incidence of motor blockade with CEI using the modified Bromage score, which may be more sensitive than the traditional Bromage score.41 The authors suggested that the greater incidence of motor blockade and subsequent higher instrumental delivery rate in the CEI group compared with other similar trials was due to the longer duration of observation in their study. However, the duration of labor was not significantly longer in this trial and was likely shorter than average. The dramatic decrease in instrumental delivery rate is likely related to the reduced motor blockade. Perhaps the CEI infusion that was started immediately after induction of analgesia or the increased number of patients who used the higher concentration 0.125% levobupivacaine PCEA option in the CEI group added significantly to the cumulative dose of levobupivacaine and subsequent increased motor blockade. The ultralow dose regimen for epidural analgesia based on the study by Capogna et al.20 and the reduced PCEA use in the IEB group and subsequent reduced motor blockade appear to eloquently display a potential benefit of IEB. Whether it was the higher PCEA use in the CEI group or the characteristics of IEB with 0.0625% levobupivacaine, they both seem to deliver appropriate analgesia, as neither group required a manual anesthetic intervention. This came at the cost of increased motor blockade and instrumental delivery in the CEI group.
This review has several limitations. There was significant inconsistency with regard to reporting of outcomes. Each of the included studies reported at least 1 primary outcome, but none of the included studies included all primary outcomes reported in this systematic review. Each study, except Sia et al.,27 found at least 1 significant difference in a primary outcome measure. Measures of analgesia such as pain scores reported using VAS, VRS, or numeric rating scales were not measured at standard intervals. In contrast, maternal satisfaction was nearly consistently reported and may represent a surrogate measure of analgesia. The study by Wong et al.28 was the only study to recruit parous subjects; in fact, they only included parturients with at least 1 previous vaginal delivery (126 subjects). The remaining studies only included uncomplicated nulliparous women. This likely limits our ability to extrapolate our conclusions to women presenting with multiple gestations and parous women. Because of the small number of studies, a meta-regression was not conducted to control for factors known to affect the outcomes of interest.
There was significant clinical heterogeneity among studies with regard to labor analgesia initiation, specific local anesthetic and concentration, and drug delivery regimens. A subgroup analysis of the effect of PCEA maintenance and CSE analgesia initiation yielded only a potential interaction between PCEA, IEB, and the duration of labor. Because of the small number of studies, the relatively youthful field of IEB, and the variety of analgesia regimens, sensitivity analysis of these dosing variables was not part of this analysis. Currently, because of IEB with PCEA equipment not being readily available, standardization of equipment among institutions is nearly impossible. Specifically, the dosing volumes and intervals varied among the studies, and it is unknown whether this influenced the reported outcomes.
Much like the debates regarding the ideal regimen of CEI combined with PCEA, the search for the ideal IEB regimen is sure to inspire future studies. Wong et al.49 have initiated this avenue of research. They recently compared 3 regimens of IEB and PCEA: 2.5 mL every 15 minutes, 5 mL every 30 minutes, and 10 mL every 60 minutes of 0.625 mg/mL bupivacaine with 1.95 µg/mL of fentanyl. The 10/60 group did consume less bupivacaine, and the 2.5/15 group appeared to require more interventions for poor analgesia, but otherwise all 3 groups were very similar with respect to mode of delivery, PCEA usage, manual anesthesia interventions, pain scores, and motor blockade. Future studies will need to be powered to detect the small differences that may exist between the extremes of bolus size. Accepting that the low-dose epidural regimens of Wong et al.49 and Capogna et al.20 are likely near the ideal concentration, the trends suggest that larger volume boluses may be required.
In summary, IEB may be associated with reduced local anesthetic consumption, shorter second stage of labor, and higher maternal satisfaction but possibly no difference in mode of delivery or required anesthetic interventions compared with CEI. As previously noted, the wide CIs for the pooled results of some of the reported outcomes do contain clinically significant differences, such as the potential for a clinically significant reduction in the instrumental delivery rate with IEB. Further research of IEB for labor analgesia is necessary before definite conclusions can be made. Current epidural pump technology does not allow using IEB with PCEA, and changing current practice would require a significant financial influx to labor wards for the required pump technology and education. On the basis of the findings of this systematic review and meta-analysis, current evidence suggests that there may be potential improvements in instrumental delivery rates and rates of anesthesia interventions, so more studies are required to conceptualize the ideal IEB/PCEA regimen and then consistently show an improvement in labor analgesia and a greater effect on obstetric outcomes. The new pump technology required for this new technique and the cost that this entails could easily be justified by improved outcomes.
Name: Ronald B. George, MD, FRCPC.
Contribution: This author helped design and conduct the study, analyze the data, and write the manuscript.
Attestation: Ronald B. George has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Terrence K. Allen, MBBS, FRCA.
Contribution: This author helped conduct the study, analyze the data, and write the manuscript.
Attestation: Terrence K. Allen has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Ashraf S. Habib, MB, ChB, MSc, MHS, FRCA.
Contribution: This author helped conduct the study, analyze the data, and write the manuscript.
Attestation: Ashraf S. Habib has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
This manuscript was handled by: Cynthia A. Wong, MD.
a January 1, 2012, to July 4, 2012—International Journal of Obstetric Anesthesia, Anesthesia & Analgesia, Anesthesiology, Canadian Journal of Anesthesia, Anaesthesia, and British Journal of Anaesthesia.
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