A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes

Grace Lim, M.D., M.S.; Francesca L. Facco, M.D., M.S.; Naveen Nathan, M.D.; Jonathan H. Waters, M.D.; Cynthia A. Wong, M.D.; Holger K. Eltzschig, M.D., Ph.D.

Disclosures

Anesthesiology. 2018;129(1):192-215. 

In This Article

Labor Analgesia and Anesthesia

Methods of Labor Analgesia

Neuraxial Analgesia: Initiation and Maintenance. Labor neuraxial analgesia is usually initiated by one of two methods: epidural or combined spinal-epidural analgesia (Figure 2).[6] Combined spinal-epidural analgesia is often used for initiation of analgesia in advanced labor because of rapid onset of effective analgesia.[7,8] Combined spinal-epidural analgesia has faster onset (2 to 5 min) than epidural analgesia (15 to 20 min), greater uniformity in sensory blockade, and improved sacral dermatome coverage.[9] While some studies report greater satisfaction and sense of control associated with combined spinal-epidural analgesia, the meta-analyses do not support this observation.[9] Some experts have argued that confirmation of correct epidural catheter placement is delayed following initiation of combined spinal-epidural analgesia; however, a 2016 study suggests that may not be the case, and favors combined spinal-epidural analgesia for earlier detection of failed epidural analgesia.[10] Other studies have shown that epidural catheters sited as part of a combined spinal-epidural technique fail less often, both during labor and for intrapartum cesarean delivery.[11,12] A possible explanation for these findings is confirmation of correct placement of the tip of the epidural needle in the epidural space by virtue of cerebrospinal fluid visualization through the spinal needle. A 2014 meta-analysis did not find a definitive benefit of combined spinal-epidural analgesia for catheter replacement rates, supplemental epidural dosing, and epidural vein cannulation; although the meta-analysis was limited by significant between-study heterogeneity.[13] A higher risk of uterine tachysystole after combined spinal-epidural analgesia than epidural analgesia has been reported and may be attributable to the rapid decrease in circulating catecholamines (which have a tocolytic effect) that accompanies rapid-onset of labor analgesia.[8]

Figure 2.

Epidural analgesia technique (A) versus combined spinal-epidural technique (B). In epidural analgesia, the epidural space is located using an epidural needle, by a loss-of-resistance technique. A 19- to 20-gauge epidural catheter is threaded into the space and used to dose medications. In combined spinal-epidural analgesia, the epidural space is located in the same fashion, and prior to threading the epidural catheter, a small 25- to 27-gauge spinal needle is introduced through the epidural needle to puncture the dura and to bolus a single dose of local anesthetic with or without opioid. The spinal needle is removed and a 19- to 20-gauge epidural catheter is threaded for subsequent dosing. Figure reprinted with permission from Eltzschig HK, Lieberman ES, Camann WR: Regional anesthesia and analgesia for labor and delivery. N Engl J Med 2003; 348:319–32.6

A modification of the combined spinal-epidural technique is dural puncture epidural analgesia.[14,15] In this technique, the epidural space is identified and the dura is punctured with a 25-gauge or smaller pencil-point spinal needle, but no intrathecal medication is injected; an epidural catheter is threaded in the routine manner. Dural puncture epidural analgesia may be associated with improved sacral analgesia compared to epidural analgesia, with less pruritus, hypotension, supplemental epidural doses, and uterine tachysystole than combined spinal-epidural analgesia.[14,15] A likely mechanism is the dural hole acts as a conduit to enhance epidural medication translocation into the intrathecal space, allowing enhanced coverage of sacral nerve roots while avoiding the side effects associated with conventional combined spinal-epidural analgesia. Dural puncture epidural analgesia may be a viable technique for patients with a suspected difficult airway or failed epidural labor analgesia, for whom confirmation of correct epidural needle placement is critical, without incurring the side effects of spinal medication dosing.

Modern labor analgesia favors initiation and maintenance of analgesia with low-dose local anesthesia and opioid solutions to minimize risks of local anesthetic systemic toxicity (unintentional intravascular injection) or high- or total-spinal anesthesia (unintentional intrathecal injection). These low-dose strategies also minimize hemodynamic effects and placental drug transfer.[16] Dilute local anesthetics reduce the risk for motor block which may contribute to instrumental delivery and postpartum nerve palsies.[17] Initiation of contemporary labor epidural analgesia combines low-dose, long-acting amide local anesthetics, typically a bolus of 5 to 15 ml bupivacaine, 0.0625% to 0.125%, with a lipid soluble opioid, typically fentanyl 50 to 100 μg or sufentanil 5 to 10 μg.[18] The drugs used to initiate combined spinal-epidural analgesia may vary based on the stage of labor. An opioid-only intrathecal dose (e.g., fentanyl 25 μg) is highly effective in treating pain associated with the first stage of labor, although it is accompanied by a high incidence of pruritus; a combination of intrathecal local anesthetic and lipid soluble opioid (e.g., bupivacaine 1.25 to 2.5 mg and fentanyl 15 μg) effectively treats somatic pain of the late first and second stages of labor.[18] Epidural analgesia is usually maintained with an infusion of bupivacaine 0.05% to 0.1% with fentanyl 1.5 to 3 μg/ml or sufentanil 0.2 to 0.33 μg/ml at a rate of 8 to 15 ml/h into the epidural space.[18] Combining local anesthetic with lipid soluble opioid allows for profound visceral and somatic analgesia. The synergy between opioid and local anesthetic medications allows dose-reduction of both drugs, minimizing side-effects.[19]

Continuous Epidural Infusion Versus Programed Intermittent Bolus. Prior to the advent of infusion pump technology, maintenance of labor analgesia occurred by manual intermittent boluses throughout labor. A major disadvantage of this maintenance strategy was that analgesia would eventually regress, leading to recurrence of pain, requiring another manual bolus; thus, analgesia was episodic. With the advent of infusion pumps, continuous epidural infusion techniques became popular. This technique resulted in more stable analgesia and reduced supplemental epidural dosing for breakthrough pain compared to manual intermittent bolus strategies.[7] As technology improved, patient-administered bolusing (patient-controlled epidural analgesia) was introduced. Evidence from randomized trials support that analgesia is superior when patient-controlled epidural analgesia is used with a background infusion compared to without a background infusion.[7,20,21] Patient-controlled epidural analgesia is preferable to fixed-rate continuous epidural infusion because of lower total local anesthetic dose consumption, lower incidence of motor blockade, and reduced need for anesthesia provider interventions.[7] Settings for patient-controlled epidural analgesia are variable, but generally include a background infusion of bupivacaine 0.05% to 0.1% with fentanyl 1.5 to 3 μg/ml or sufentanil 0.2 to 0.33 μg/ml at 5 to 8 ml/h, a bolus of 5 to 10ml, and a lock-out interval of 10 to 20 min.[16]

Programed intermittent epidural bolus has been recently investigated for maintenance of labor epidural analgesia. Rather than administering the maintenance dose as a continuous infusion, with or without patient-controlled epidural analgesia, it is administered by the infusion pump programed to deliver boluses of epidural solution at regular intervals. The likely mechanism of improved analgesia is greater medication spread in the epidural space; the epidural catheter is usually sited in a midlumbar epidural interspace, and satisfactory labor analgesia requires coverage of both low-thoracic and sacral dermatomes (Figure 3). One dosing strategy involves a solution of bupivacaine 0.625% with fentanyl 2 μg/ml with an intermittent epidural bolus of 6-ml every 30 min, in addition to patient-controlled epidural analgesia allowing a 5-ml bolus with 10-min lockout.[22] The programed intermittent epidural bolus technique allows maintenance of analgesia with less local anesthetic without impairing maternal analgesia and satisfaction, is associated with fewer supplemental epidural doses (less breakthrough pain), and has reduced risk for motor block and instrumented delivery.[22–25] In one trial, motor block occurred more frequently (odds ratio 21.2, 95% CI, 4.9 to 129.3, P < 0.001) and earlier in women randomized to receive continuous epidural infusion compared with a programed intermittent epidural bolus to maintain analgesia. Instrumental delivery occurred more frequently in the continuous epidural infusion group (20% vs. 7%, P = 0.03).[23] A meta-analysis of nine trials showed lower local anesthetic dose and higher satisfaction scores with programed intermittent epidural bolus.[25] Higher local anesthetic doses may be associated with reduced pelvic floor muscle tone, reduced mobility, impaired Valsalva maneuvers, and risk for instrumental delivery.[26] Administration of local anesthetic by continuous infusion is inherently safer than bolus dosing. Bolus dosing by a human (anesthesia provider or patient) offers safety because the presence of pain suggests that the catheter is not malpositioned in the subarachnoid space. A potential disadvantage of programed intermittent epidural bolus is unintentional high neuroblockade that may accompany catheter migration into the intrathecal space.[27]

Figure 3.

Maintenance of epidural analgesia by continuous epidural infusion versus programed intermittent epidural bolus. Differences in spread (blue pigment) of equivalent doses of local anesthetic over course of 1 h in (A) continuous epidural infusion and in (B) programed intermittent epidural bolus are depicted.

Newer equipment now enables use of programed intermittent epidural bolus in clinical practice. The focus of current research is identifying optimal settings for epidural bolus volume and interval, bolus infusion rate, and local anesthetic concentration.[28]

Systemic Opioids for Labor Analgesia. Systemic opioids are an alternative option for women for whom neuraxial analgesia may be contraindicated, cannot be achieved (technical failure to place an epidural catheter), or who prefer an alternative method of labor analgesia. A common approach involves fentanyl patient-controlled intravenous analgesia, typically 25 μg every 10 to 15 min, with an hourly lockout of 100 μg.[29] In the past decade, remifentanil patient-controlled intravenous analgesia has gained popularity due to its titratability and short latency (60 to 90 s). However, timing the self-administered bolus dose with the peak of uterine contractions is difficult; the peak analgesic effect typically occurs with the second contraction after the button is pushed, and contraction frequency may be irregular. Because remifentanil is rapidly metabolized by plasma esterases, it is appealing for reduced fetal placental transfer, and for rapid fetal clearance of drug. Remifentanil patient-controlled intravenous analgesia provides reasonable analgesia and maternal satisfaction, but maternal sedation, respiratory depression, and apnea are well-described.[30,31] In one trial, the risk for maternal oxygen desaturation was significantly higher in women receiving remifentanil compared to fentanyl.[32] Monitoring of respiratory variables (respiratory rate, end-tidal carbon dioxide, pulse oximetry, heart rate, and pulmonary index) has low positive predictive values for surveillance of maternal apnea.[33] Therefore, remifentanil patient-controlled intravenous analgesia should be accompanied by continuous respiratory monitoring; we believe this monitoring is ideally achieved by 1:1 provider observation (nurse, midwife, or anesthesia provider).[34,35]

Remifentanil patient-controlled intravenous analgesia is not superior to neuraxial labor analgesia techniques. A meta-analysis of five randomized trials found higher pain scores in women receiving remifentanil.[36] However, one randomized trial noted that while pain scores reductions were greater with neuraxial analgesia, patient satisfaction scores were not different.[30] These findings support the repeated observation that patient satisfaction for labor analgesia is not driven solely by reductions in pain intensity. In a 2014 to 2015 survey, only 36% (95% CI, 26 to 46) of academic obstetric units in the United States used remifentanil for labor analgesia, with most doing so less than five times a year.[35]

Compared to remifentanil, fentanyl patient-controlled intravenous analgesia for labor analgesia has a lower rate of maternal sedation and respiratory depression; however, it has a higher rate of neonatal respiratory depression requiring resuscitation at delivery.[37] In one study, 59% of neonates whose mothers used fentanyl compared with 25% for remifentanil patient-controlled intravenous analgesia required resuscitation (odds ratio, 4.33; 95% CI, 1.75 to 10.76).[37] Remifentanil may offer modest analgesic advantage over fentanyl (mean visual analog scale score, remifentanil: 46 mm vs. fentanyl 60 mm, P < 0.01).[32]

Nitrous Oxide. There is a renewed interest in the United States in nitrous oxide for labor analgesia, although it has been integrated into labor analgesia in other parts of the world (e.g., Europe) for many years. Women who use nitrous oxide report improved maternal satisfaction and coping compared to no analgesia, although its analgesic efficacy is inferior to neuraxial labor analgesia.[38] These findings are not surprising, given that maternal experience is known to be influenced by factors such as a sense of control and ability to participate in decision-making, and is not exclusively influenced by the provision of effective labor analgesia.[39]

Nitrous oxide for labor analgesia has a long history of safe maternal use, although rigorous study is lacking and questions remain regarding neonatal-childhood outcomes and occupational risks of exposure.[29] In experimental models and in some clinical settings, nitrous oxide has been suggested to be neurotoxic and genotoxic, with potential adverse effects on the hematologic and immunologic systems.[40–43] Several studies have reported no adverse neonatal events of this nature after maternal exposure to nitrous oxide for labor, although these studies have been limited by flaws in study design, conduct, analysis, and reporting.[38] Nitrous oxide is a potent greenhouse gas, although some experts contend that medical use of nitrous oxide has little environmental impact.[40] Occupational exposure (reproductive toxicity) may be a concern if nitrous oxide delivery does not employ robust scavenging equipment.[40]

Nitrous oxide for labor analgesia and neuraxial analgesia result in similar degrees of maternal satisfaction. Its analgesic efficacy exhibits high inter-individual variability. However, interest in increasing women's choices for labor analgesia and patient satisfaction in United States hospitals makes offering nitrous oxide during labor analgesia an attractive option.

Pharmacogenomics and Pain Genetics. Scientific advancements in genetic medicine will likely allow development of personalized pain management strategies in the future, but our current knowledge is still inadequate for precision labor analgesia. For example, a single nucleotide polymorphism of the μ-opioid receptor gene (OPRM1, A118G) may be present in up to 30% of the obstetric population, and is linked to altered responsiveness to neuraxial opioids; the polymorphism increases binding and potency of β-endorphins.[44] These properties are linked to later request for analgesia and lower neuraxial fentanyl and sufentanil dose requirements (ED50) in labor, compared to women with the wild-type alleles.[44,45] In apparent contrast to these study results are the findings of a study from Asia; women who were homozygous for the A118G polymorphism had increased opioid dose requirements after cesarean delivery, and more breakthrough pain.[46] A 2009 meta-analysis of studies of the effect of the OPRM1 A118G polymorphism on pain included studies from North America, Asia, and Europe and found no effect of the polymorphism on opioid dose requirement.[47]

The influence of genetic polymorphisms on labor progress has been investigated. Terkawi et al. found that polymorphisms in the β2-adrenergic receptor gene were linked to labor pain; however, these polymorphisms explained less than 1% of the inter-subject variability.[48] Similarly, catechol-O-methyltransferase and oxytocin gene receptor polymorphisms were linked to slower transitions to active labor and slower latent phase of labor.[49] While genetic factors will likely not entirely explain inter-individual differences in labor pain and labor progress, continuing advances in pain genetics and pharmacogenetics may contribute to our future ability to provide individualized therapies for labor pain and analgesia.

Effect of Labor Analgesia on Labor Progress and Mode of Delivery

Labor Neuraxial Analgesia and Risk for Instrumental Delivery. Epidural labor analgesia has been linked to increased risk for instrumental vaginal delivery, although the nature of the relationship is controversial. Challenges to definitive investigations include obstetrician practice and the likelihood that instrumental delivery is attempted more often when effective neuraxial analgesia is present (Table 1). Understanding the relationship between neuraxial analgesia and operative delivery is important because modern obstetrical skills in instrumental vaginal delivery is declining;[18,50] this trend may result in rising, indirect associations between labor neuraxial analgesia and increased rates of second stage cesarean deliveries.

Meta-analyses of randomized trials comparing labor neuraxial analgesia to systemic opioids found that the mean duration of the first and second stages of labor were prolonged in neuraxial analgesia groups by 30 min and 15 min, respectively, and the rate of instrumental vaginal delivery was increased in women receiving neuraxial analgesia (relative risk, 1.42; 95% CI, 1.28 to 1.57; 23 trials, 7,935 women).[51] However, many of the trials that were included in the meta-analyses used epidural bupivacaine concentrations of 0.25%. This concentration is considered high, by modern standards. Addressing this concern, the Comparative Obstetric Mobile Epidural Trial Study compared low-dose labor epidural techniques to a "traditional" or high-dose technique in a randomized controlled design.[52] The high-dose group received epidural analgesia initiated with 10 ml bupivacaine 0.25% (25 mg), with subsequent boluses of 10-ml bupivacaine 0.25% (25 mg) on request (but no more than hourly). One low-dose group received epidural bupivacaine 0.1% with fentanyl 2 μg/ml; analgesia was maintained with an infusion. The second low-dose group had combined spinal-epidural initiation (spinal dose: bupivacaine 2.5 mg and fentanyl 25 μg) and maintenance analgesia by intermittent injections of 0.1% bupivacaine with fentanyl. The investigators found that high-dose epidural analgesia was associated with a reduced rate of normal spontaneous vaginal delivery. These differences were explained by reduced instrumental vaginal delivery rates in the low-dose groups.[52] There was no difference in total dose of local anesthetic between groups, likely due to method of analgesia maintenance: the high-dose group had medication delivered by intermittent bolus, whereas the low-dose group had medication delivered by continuous infusion. Specific analgesic technique and drug combination/dose may be influential; a meta-analysis comparing combined spinal-epidural and epidural analgesia showed that instrumental deliveries were lower in combined spinal-epidural compared to "high-dose" epidural analgesia, but not compared to "low-dose" epidural analgesia.[9] The true effect and impact of labor epidural analgesia on risk for instrumental delivery remains poorly understood.

More recently, an observational study of more than 600,000 deliveries in the Netherlands did not demonstrate a change in instrumental delivery rates despite almost tripling the labor neuraxial analgesia rate from 7.7 to 21.9% over 10 yr.[53] A meta-analysis of 28,443 patients showed no effect of increasing availability of labor neuraxial analgesia on instrumental delivery rates.[54] Concentration and motor function may be important; a meta-analysis of 11 randomized trials compared the instrumental delivery rate in high- versus low-concentration local anesthetic solution groups, and low-concentration strategies were linked to reduced risk for assisted vaginal delivery and motor block.[17] Many studies have noted a relationship between total local anesthetic dose and motor blockade, but the association between motor blockade and instrumental delivery has been inconsistent.[18] Although controversy persists, the available evidence suggests that functional labor analgesia is associated with risk for instrumental delivery, possibly by virtue of analgesic density and motor impairment.[18] Instrumental vaginal delivery may increase risk for lacerations and other perineal injuries, neonatal facial or cranial injuries, and pelvic organ prolapse. Given these undesirable outcomes, the goal of modern labor epidural analgesia favors minimizing motor blockade by initiating and maintaining analgesia using low-concentration local anesthetic solutions.[7] Nevertheless, minimizing risk for instrumental delivery while maximizing patient comfort requires skillful attention to individual patient needs and clinical circumstances.

Mode of Delivery. Early observational studies identified an association between neuraxial labor analgesia and increased rates of cesarean delivery; however, the relationship is not surprising given that women requesting neuraxial analgesia are more likely to be experiencing more painful labor.[18] Factors associated with more painful labor are themselves associated with an increased risk for cesarean delivery (e.g., fetal malrotation, fetal-pelvic disproportion, dysfunctional labor).[18] Early trials were limited by methodologic concerns, including mixed populations of nulliparous and parous women, use of different types of neuraxial analgesia, inconsistent density of blockade, and high protocol violation and study group crossover rates.[55–57] A study from Parkland Hospital in Dallas, Texas (where the patient population is primarily indigent and labor is managed by the same group of obstetricians and midwives) compared the cesarean delivery rate in women receiving epidural analgesia to women receiving systemic meperidine analgesia.[55] A per protocol analysis suggested that the cesarean delivery rate was higher among women who used epidural analgesia (9% vs. 3.9%).[55] However, the rate of crossover from meperidine to the epidural group was approximately 33%. After performing an intent-to-treat analysis, the cesarean delivery rate was not different (6%) between groups.[58] In a subsequent study at the same hospital, there was no difference in cesarean delivery rates when intravenous patient-controlled analgesia was used as a control. Use of this methodology resulted in better analgesia in the control group; only 5 of 357 patients crossed over.[59]

A 2011 systematic review of 38 randomized trials did not identify a link between labor epidural analgesia and risk for cesarean delivery.[51] Impact studies (comparison of the institution's cesarean delivery rate before and after the introduction of a neuraxial labor analgesia service) have shown no association between labor neuraxial analgesia and cesarean delivery.[54,60–62] Altogether, although the debate persists, the evidence does not support that neuraxial labor analgesia increases the risk for cesarean delivery.[7]

"Early" labor epidural analgesia (i.e., epidural analgesia performed during the latent phase of labor) was historically believed to be a risk factor for cesarean delivery. Observational trials suggested that women who requested neuraxial analgesia early in labor (commonly defined as cervical dilation less than 4 cm) had a higher cesarean delivery rate.[63] This translated into a common practice among obstetric practitioners in the 1990s, advising their patients to avoid epidural analgesia in early labor.

In contrast to observational trials, multiple randomized control trials comparing early to later initiation of labor neuraxial analgesia failed to find a link between early use and risk for cesarean delivery (Table 2).[64–70] These trials compared early labor neuraxial analgesia and systemic opioid analgesia; women randomized to receive early systemic opioid analgesia received neuraxial analgesia later in labor. The trials were well controlled; and crossover rates were not excessive. In two separate trials, Chestnut et al. found early epidural analgesia among nulliparous women was not associated with increased risk for cesarean delivery in both spontaneous and oxytocin-induced or oxytocin-augmented labor.[65,66] These findings were important because they supported the provision of epidural analgesia during latent labor, whereas this practice was formerly thought to increase risk for cesarean delivery. Later, Wong et al. also found no difference in the rate of cesarean delivery among women who received combined spinal-epidural analgesia at less than 4 cm of cervical dilation compared with those who received early labor systemic opioid analgesia followed by epidural analgesia later in labor; onset and intensity of analgesia were superior in the combined spinal-epidural analgesia group.[64] Ohel et al. found similar results; the rates of cesarean delivery in women who received early compared with late epidural analgesia were similar (13% vs. 11%, P = 0.77).[68]

Considering these findings, the data linking labor epidural analgesia to cesarean delivery may be better explained by the observation that women with more painful labors, especially early labor pain, are more likely to require cesarean deliveries due to obstetrical factors such as fetal macrosomia, malrotation, and dysfunctional labor.[71–73] The practice of avoiding neuraxial labor analgesia in early labor for fear that it will adversely affect the mode of delivery should be completely abandoned.[7]

Progress of Labor. While some studies have demonstrated a modest prolongation of the first stage of labor (mean approximately 30 min),[74] others have shown neuraxial analgesia is associated with faster labor. Wong et al. and Ohel et al. found early labor neuraxial analgesia resulted in faster labor compared to treating early labor pain with systemic opioids and initiating neuraxial analgesia later in labor.[64,68] A 2017 meta-analysis did not find a relationship between low-concentration epidural analgesia and the duration of labor; however, studies were of low quality and the CIs were wide.[75]

The reasons for the conflicting results are multifold. Methodologically, trials differ in how they define the onset of labor. Epidural analgesia may delay cervical examination due to effective analgesia (examinations establishing full cervical dilation are typically deferred until the parturient complains of rectal pressure). Epidural analgesia has been linked to both increased and decreased uterine activity.[8,76–78] Decreased uterine activity may be explained by coadministration of intravenous fluid, reducing circulating antidiuretic hormone, and reducing endogenous oxytocin (both hormones are produced by the posterior pituitary gland).[77] Increased uterine activity may be explained by a rapid reduction in circulating catecholamines associated with initiation of analgesia;[8,78] the withdrawal of β2-adrenergic activity (tocolytic) may result in frequent and more intense uterine contractions leading to uterine tachysystole. Heterogeneous effects of epidural analgesia on uterine activity and first stage of labor may also be explained by variability in neurophysiologic responses to labor, pain, and analgesia.[79]

Effective epidural analgesia is associated with a prolonged second stage of labor, with an estimated mean difference of 15 min, which is not clinically meaningful.[74] However, the duration of the second stage of labor at the 95th percentile may be prolonged up to 2 h in both nulliparous and parous women with epidural analgesia.[80,81] The impact of prolonged second stage of labor on maternal and neonatal outcomes deserves scrutiny. Older studies have not shown adverse maternal or neonatal outcomes associated with prolonged second stage of labor, provided that the fetal heart rate tracing remains reassuring and there is progressive fetal descent.[82–84] However, in a large multicenter observational study, longer periods of active pushing were associated with an increased relative risk for neonatal complications, such as mechanical ventilation, sepsis, brachial plexus palsy, encephalopathy, and death, although the absolute risk was low.[85] Other studies have shown an increased risk of adverse maternal outcomes (e.g., chorioamnionitis, high-degree lacerations, atony, hemorrhage, fever) for every additional hour spent in the second stage of labor.[86,87] Given the association between prolonged second stage of labor and adverse maternal and neonatal outcomes, the effect that neuraxial analgesia may have on labor duration remains an important research question.

Neuraxial Anesthesia for External Cephalic Version. External cephalic version is a procedure wherein a breech fetus at 36 to 39 weeks gestation is manually rotated to the vertex presentation, permitting a trial of labor and vaginal delivery. The procedure is an important strategy for prevention of primary cesarean delivery (17% of primary cesarean deliveries are due to fetal malpresentation).[88] Prevention of primary cesarean delivery is an important public health concern given the high rates of cesarean delivery, maternal morbidities associated with cesarean delivery compared to vaginal delivery, and increasing healthcare costs and maternal risk in subsequent pregnancies after primary cesarean delivery. Neuraxial anesthesia for attempted external cephalic version is associated with a higher success rate.[89]

The findings of early studies of the role of neuraxial anesthesia in external cephalic version were equivocal.[90,91] Some obstetricians are concerned that neuraxial analgesia will mask pain related to uterine rupture or placental abruption, rare but catastrophic complications of external cephalic version. A 2011 meta-analysis allays these concerns, showing no differences in the rates of placental abruption or uterine rupture in neuraxial anesthesia versus control groups who received no analgesia or systemic opioid analgesia.[92] Risk for cesarean delivery for nonreassuring fetal heart rate was also not different between neuraxial anesthesia and control groups.

Meta-analyses of randomized control trials have identified a 13 to 50% increase in the rate of successful external cephalic version with neuraxial anesthesia; most women who have a successful external cephalic version have a successful vaginal delivery.[89,92,93] The results of early meta-analyses suggested that the success rate may be dose-dependent: denser neuroblockade has a higher success rate.[93] Surgical-level neuraxial anesthesia is postulated to enhance relaxation of abdominal wall musculature, assisting the manual efforts of the obstetrician. However, a 2017 study in which women were randomized to receive combined spinal-epidural analgesia with intrathecal fentanyl combined with varying doses of bupivacaine (2.5, 5, 7.5, and 10 mg) did not support a dose-response effect on external cephalic version success rate (50, 52, 52 and 49%, respectively; P = 0.99).[94] There were no differences in obstetrician rating for abdominal relaxation. An advantage of neuraxial anesthesia for external cephalic version is the ability to convert to surgical anesthesia in the event of emergency cesarean delivery. Disadvantages of neuraxial analgesia/anesthesia for external cephalic version include hypotension and delayed hospital discharge, both of which may be dose-dependent. Hypotension is typically easily treated, but requires close monitoring. An economic analysis on the use of neuraxial anesthesia for external cephalic version found it to be cost-effective, assuming an improved success rate of at least 11% from a baseline of 38%.[95] This finding is explained by the large differences in costs between vaginal delivery and cesarean delivery.

Oral Intake in Labor. Aspiration pneumonitis or solid gastric content asphyxiation was a leading cause of anesthesia-related maternal mortality.[3] The stomach shifts cephalad, displacing the lower-esophageal sphincter into the thorax.[96] Lower esophageal sphincter pressure declines by 50% during pregnancy.[97] Reduced motilin produces slower intestinal transit times.[98] While pregnancy does not increase gastric emptying time, endogenous or exogenous opioids prolong gastric emptying times.[99,100]

To address aspiration-related maternal mortality in the middle part of the twentieth century, the following practices became the cornerstone of modern obstetric anesthesia practice: (1) widespread use of neuraxial anesthesia; (2) oral intake restrictions during labor; (3) preanesthetic antacid administration; (4) rapid-sequence induction for general anesthesia; (5) improvements in anesthesia training; and (6) improvements in advanced airway devices. These practices are reflected in current American Society of Anesthesiologists recommendations.[7] Because of these practices, maternal mortality from aspiration has declined to extremely low levels (estimated case fatality rate, 6.5 per million anesthetics in the Unites States).[5,101,102] Closed claims analysis shows a significant reduction in malpractice claims from aspiration.[103] Because of the modern rarity of aspiration-related mortality, and with growing interest in limiting medical interventions during low-risk labor, liberalizing oral intake during labor is appealing.[104] The World Health Organization advocates no interference with a woman's desire to eat and drink during low-risk labor.[105] Liberalizing oral intake might have advantages for patient satisfaction, and it seems intuitive that providing energy during a demanding metabolic period might improve outcomes. Nil per os practices in pregnancy have been linked to a state of "accelerated starvation" due to shifts to glycogenolytic and gluconeogenesis metabolic pathways.[106]

Early studies shed light on outcomes with liberalized oral intake strategies in labor.[107–109] In one study, women were randomized to a light meal or to water; epidural analgesia with opioid-containing solutions was permitted.[109] Women in the light diet group had lower plasma β-hydroxybutyrate and nonesterified fatty acids, indicating ketosis prevention. However, there were no differences in lactate, labor duration, Apgar scores, and umbilical cord blood gases. Light diet consumers were more likely to vomit, and vomited higher volumes of particulate matter, during labor. In another study, rates of vomiting were similar between water and sports drinks, while reduced markers of ketoacidosis without increases in gastric volumes were found in sports drink consumers.[107] A large trial found no differences in the rate of vaginal delivery, duration of labor, cesarean delivery, or vomiting.[108]

Meta-analyses in low-risk deliveries show no effect of food intake on mode of delivery and neonatal well-being, although pooled data were insufficient to address the risk for aspiration.[110,111] There are two possible interpretations of these data. First, given the contemporary rarity of aspiration, maternal wishes should take priority, and oral intake guidelines liberalized to allow maternal decision-making for light meals during low-risk labors. Alternatively, women seem to tolerate limited oral intake in labor without negative consequences, and considering the large decrease in maternal mortality since nil per os strategies were implemented, there is no need to liberalize oral intake restrictions. Current American Society of Anesthesiologists guidelines allow clear liquid intake in uncomplicated labor and complete avoidance of particulate and solid food.[7] Nil per os strategies for parturients undergoing elective surgery (e.g., scheduled cesarean delivery or postpartum tubal ligation) include fasting 2 h for clear liquids and 6 to 8 h for solid food, depending upon fat content.[7]

Considering the historical context in which nil per os strategies developed, along with ethical and logistical challenges of conducting a trial addressing harm, we will likely continue seeing global and cultural discrepancies on oral intake during labor. Based on available data and history, our practice is to avoid solid food and particulate liquid ingestion in labor, particularly if parenteral or neuraxial opioids were administered, to allow glucose-containing clear liquids as tolerated, and to restrict oral intake in individuals after considering comorbidities that may increase the risk for cesarean delivery or aspiration (e.g., obesity, diabetes mellitus, suspected difficult airway, and nonreassuring fetal heart rate tracing).

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