Does neuraxial labor analgesia affect the outcome of labor, specifically the mode of delivery and the duration of labor? This question has been asked for almost half a century. Early observational trials found that neuraxial analgesia was associated with an increased risk of operative delivery and prolonged duration of labor. For years, the association was assumed to be causal. Laboring women were told that “the epidural” would slow down labor and increase the risk of cesarean delivery. Eventually, however, randomized controlled trials demonstrated that neuraxial labor analgesia does not increase the risk of cesarean delivery.1 This conclusion is supported by the results of impact trials that compared the rate of cesarean delivery in institutions before and after the general availability of neuraxial analgesia—the cesarean delivery rate did not change over time.2 The different results of observational and controlled trials suggest that women who request neuraxial analgesia are inherently different than women who do not; the baseline risk of cesarean delivery is greater in women who request neuraxial analgesia. A likely explanation is that women at increased risk for cesarean delivery have greater pain during labor and thus request analgesia at a higher rate. Bigger babies, malpositioned babies, and dysfunctional labor hurt more and are also associated with an increased risk of operative delivery.
The data regarding the influence of neuraxial labor analgesia on operative vaginal delivery are less clear. Although most randomized controlled trials, and a meta-analysis that includes over 27 trials and 8417 women, found the neuraxial analgesia does not increased the rate of cesarean delivery, these same trials and meta-analysis found an increased risk for instrumental vaginal delivery in women randomized to receive neuraxial analgesia compared with systemic opioid analgesia (relative risk [RR] 1.42, 95% confidence interval [CI], 1.28–1.57).1 In contrast, most impact trials found no difference in the risk of instrumental vaginal delivery between the “before” period (no neuraxial analgesia available) and “after” period. In a meta-analysis, the difference in the rate of instrumental vaginal delivery between the “before” and “after” periods was 0.76% (95% CI, −1.2% to 2.8%).2 Thus, whether neuraxial analgesia causes an increased risk of instrumental vaginal delivery is still a matter of animated discussion among obstetricians, anesthesiologists, midwives, and labor nurses. Parturients, of course, are receiving conflicting information about this important outcome.
In this issue of Anesthesia & Analgesia, Wang et al3 report the results of a new systematic review and meta-analysis of randomized controlled trials comparing neuraxial with systemic opioid analgesia on labor outcomes. The review updates previous meta-analyses by excluding studies in which women in the neuraxial group received high-concentration local anesthetic solutions. Over the past 30 years, a remarkable shift in practice was driven, in part, by observational and randomized controlled trials that suggest women who receive higher concentration local anesthetic solutions for initiation and maintenance of neuraxial analgesia have a higher incidence of instrumental vaginal delivery. In a 2013 systematic review and meta-analysis comparing high-concentration (bupivacaine >0.1% or ropivacaine >0.17%) with low-concentration solutions, the odds for instrumental vaginal delivery were significantly lower in women who were randomized to receive low-concentration solutions (odds ratio 0.70, 95% CI, 0.56–0.86).4 Consequently, most contemporary practices rely on low-concentration local anesthetic solutions combined with a lipid-soluble opioid (fentanyl or sufentanil [neuraxial fentanyl and sufentanil is an off-label use]) to maintain neuraxial labor analgesia.
In light of this shift in clinical practice, the Wang et al3 meta-analysis included only randomized controlled trials comparing women who received maintenance of epidural analgesia with low-concentration local anesthesia (bupivacaine ≤0.1% or ropivacaine ≤0.17%) versus nonneuraxial analgesia (eg, systemic opioid, nitrous oxide, nonpharmacologic analgesia). The primary outcomes were the incidence of instrumental vaginal delivery and duration of the second stage of labor. Among 8 trials with approximately 1500 participants,3 the authors found no difference in the incidence of instrumental vaginal delivery between the 2 groups (RR 1.52, 95% CI, 0.97–2.40) or the median duration of the second stage of labor (mean difference 5.7 minutes, 95% CI, −6.4 to 17.8). However, the authors appropriately noted that the results were based on small studies of low quality. Wang et al3 noted substantial heterogeneity (I2 = 94%) among trials for the duration of the second stage. The authors were unable to explain the heterogeneity using sensitivity analyses. The current meta-analysis is underpowered to reach a valid conclusion about the relative risk of instrumental vaginal delivery; the 95% CI contains a clinically significant difference in risk between groups (ie, relative risk as high as 2.40). Although Wang et al3 state that their results differ from older meta-analyses that found increased risk of instrumental vaginal delivery between groups, in fact, they do not; the 95% CIs of relative risk of the new and older analyses overlap. The same is true for the duration of labor. In the most recent meta-analysis of all randomized controlled trials (including both high- and low-concentration studies), the duration of the second stage was 13.7 minutes (95% CI, 6.7−20.7 minutes) longer in the neuraxial compared with the nonneuraxial group.1
The actual prolongation of the second stage of labor associated with epidural analgesia may be longer than reported. Measurement of duration requires a defined start and end time. The end time for the second stage of labor is definitive and easy to measure: delivery of the fetus. The start time is defined as full cervical dilation (10 cm), but is much harder to measure. Documentation of full cervical dilation requires an experienced provider to perform a cervical examination. Examinations during labor are often performed intermittently and only for specific reasons, for example, the parturient reports rectal or vaginal pressure, suggesting that the cervix is fully dilated. Women with effective neuraxial analgesia may report rectal pressure at a later stage (ie, greater degree of fetal descent) than parturients without neuraxial analgesia. Thus, because the start time for the second stage of labor will be diagnosed later in the parturient with neuraxial analgesia, the calculated duration will be artificially shortened.
Although a median difference of <15 minutes can be dismissed as a reasonable tradeoff for high-quality pain control, differences at the 95th percentile may be clinically important.5 In an observational trial from the Consortium on Safe Labor Practice, the 95th percentile in the duration of the second stage of labor was approximately 50 minutes longer among those nulliparous women in spontaneous labor who selected neuraxial analgesia compared with those who did not.6
Further work is needed to define the relationship between prolonged second stage of labor and adverse maternal and/or neonatal outcomes. In general, studies have not found an association between the duration of the second stage and adverse neonatal outcomes in nulliparous women.7 In contrast, prolonged second stage of labor is associated with chorioamnionitis, third- and fourth-degree perineal lacerations, and postpartum hemorrhage.7 It is not clear, however, whether this relationship is causal, that is, whether the chicken or the egg came first (ie, did the chorioamnionitis cause the prolonged labor or did the prolonged labor cause the chorioamnionitis?). Given the current evidence, the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine consensus document states that “a specific absolute maximum length of time spent in the second stage of labor beyond which all women should undergo operative delivery has not been recommended” (grade of recommendation 1C).5 At least 3 hours of pushing should elapse in nulliparous women with epidural analgesia before arrest of labor in the second stage is diagnosed and longer durations may be appropriate on an individualized basis (grade 1B).
In contrast to the duration of the second stage, any increased rate of instrumental vaginal delivery observed in women with epidural analgesia is likely an epiphenomenon. None of the observational or randomized controlled trials comparing neuraxial analgesia with a control group was blinded. The obstetricians making the decision about mode of delivery had knowledge of group allocation. If neuraxial analgesia does prolong the second stage of labor, obstetricians may be more likely to assist delivery in women with neuraxial analgesia. Ironically, they may be more likely to apply forceps because patients have good analgesia. The degree of heterogeneity among trials as well as the finding from impact trials that the introduction of neuraxial analgesia services did not alter the rate of instrumental vaginal delivery supports the hypothesis that neuraxial labor analgesia may be negatively associated with spontaneous vaginal delivery because of practice variation.
Over the past several decades, the rate of cesarean deliveries has risen while the rate of operative vaginal deliveries has decreased. Fewer obstetricians are skilled at operative vaginal delivery thus they will be less willing to facilitate vaginal delivery, resulting in a further increase in the rate of cesarean delivery.5,8 Some cesarean deliveries are indicated to save lives. However, studies have identified marked variability in the cesarean delivery rate across individual providers, hospitals, and regions. This finding suggests that factors other than patient risk factors such as practice style and environment, patient preferences and culture, and insurance status, among others, contribute to the decision to perform a cesarean delivery and that many cesarean deliveries are performed unnecessarily.5 Given evidence that cesarean delivery is associated with adverse neonatal and maternal outcomes, there is a nationwide effort to decrease the cesarean delivery rate by addressing modifiable factors. The Centers for Medicare and Medicaid Services, The Joint Commission, the Leapfrog Group, and the American College of Obstetricians and Gynecologists recommend that the rate of cesarean delivery in the Nulliparous Term Singleton Vertex population be used as a quality metric. One way to decrease the cesarean delivery rate in Nulliparous Term Singleton Vertex women is to encourage operative vaginal delivery in appropriate individuals.5 Effective epidural analgesia could actually facilitate safe and comfortable operative vaginal delivery!
The optimal analgesic distribution and density likely vary among individual patients. Use of low-concentration local anesthetic–opioid solutions is the current standard. To successfully use these solutions, some type of titratable analgesia (eg, patient-controlled epidural analgesia) is necessary or a significant number of women will suffer breakthrough pain. Although it is tempting to administer the effective dose for 95% of women (ED95), this will result in an overdose in most women and may contribute to adverse outcomes (prolonged second stage of labor and operative vaginal delivery). The paper by Wang et al,3 considered alongside a large body of existing evidence, suggests that we should continue to work to tailor our analgesia techniques to individual parturients and improve our techniques so that any negative impact on the progress of labor and mode of delivery is minimized.
Name: Cynthia A. Wong, MD.
Contribution: This author conceived the editorial and wrote the manuscript.
Conflicts of Interest: Cynthia A. Wong was the previous Section Editor for Obstetric Anesthesiology for Anesthesia & Analgesia.
This manuscript was handled by: Jill M. Mhyre, MD.
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