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In the United States, analgesia for labor and delivery is safer than ever. Anesthesia-related maternal mortality has decreased from 4.3 per million live births during the years 19791981 to 1.7 per million live births during the years 19881990 (1). The decrease in the mortality rate appears to be related to the increased use and improved safety of regional anesthesia techniques. Despite the advances that anesthesiologists have made, there is concern that neuraxial analgesia may have negative ramifications for the mother and/or the fetus. These concerns have centered on the impact of epidural analgesia on 1) the cesarean delivery rate, 2) breast feeding difficulties, and 3) maternal pyrexia. We critically reviewed and analyzed the literature to determine if labor epidural analgesia has an impact on either the mother or neonate regarding these three issues. Furthermore, a relatively new labor analgesia technique, combined spinal-epidural analgesia, is now available. Risks and benefits of this procedure will also be reviewed.
A computerized and manual literature search was conducted in January, 1999. We sought all relevant English language publications regarding epidural or spinal analgesia and cesarean delivery, breast feeding, and pyrexia. The key words used for searching included: breast feeding, cesarean delivery, complications, epidural anesthesia, labor and delivery, parturient, pyrexia, regional anesthesia, spinal anesthesia, and temperature. Each of the pertinent publications references were then reviewed for further relevant publications.
The morbidity, mortality, and cost for women undergoing cesarean delivery are greater than for women who have a vaginal delivery. Epidural analgesia may be associated with an increased risk of cesarean delivery for dystocia (2), although a cause and effect relationship has not been proven. Similarly, pain is associated with dystocia but is not the cause (3). Investigators have taken three approaches to analyze the effect of epidural analgesia on the cesarean delivery rate: 1) impact studies, 2) retrospective studies, and 3) prospective studies.
Impact Studies We are aware of five studies that evaluated whether the initiation of an on-demand epidural anesthesia service influenced the cesarean delivery rate (48). No study found a significant change in the cesarean delivery rate, despite large increases in the epidural anesthesia rate (Table 1). The obvious limitation with impact studies is that other factors may have also changed. Obstetricians accustomed to managing labor without an epidural anesthetic may alter their practice in subtle ways that may affect the cesarean delivery rate.
In contrast to these studies that describe the effect of adding an epidural service, Johnson and Rosenfeld (9) analyzed the data from their hospital when an on-demand epidural service was abruptly removed because of a change in healthcare reimbursement. There was no significant difference in the cesarean delivery rate between the two time periods (18% vs 24%), despite the sudden decrease in the epidural rate (71% vs 27%).
Retrospective Studies
Prospective Studies A prospective, randomized, double-blind study is the best way to establish a cause-and-effect relationship between two variables (Table 3). However, this type of study, with regard to epidural analgesia and cesarean delivery rate, is difficult to perform. At many medical centers, epidural analgesia is expected by both the patient and the obstetrician. If consent is obtained, cross-over between the epidural and nonepidural groups is difficult to prevent. Furthermore, it is impossible to blind the obstetrician to the patients assigned treatment group. We will review all of the prospective and randomized studies concerning epidural analgesia and the cesarean delivery rate.
Noble et al. (15) randomized women of mixed parity to receive either an epidural anesthetic or parenteral meperidine. Of the 245 women enrolled, 43 were excluded after labor commenced. The most common reason for exclusion in the nonepidural group was that the woman was experiencing pain and wanted an epidural anesthetic or, in the epidural group, that labor progressed too rapidly, and an epidural anesthetic could not be administered. Therefore, women at low risk for cesarean delivery were excluded from the epidural group, and high-risk patients were excluded from the nonepidural group. There was only 1 (1%) cesarean delivery in the epidural group and 3 (3%) in the nonepidural group. Problems with this study are as follows: 1) a combination of nulliparous and multiparous women were enrolled, 2) the management of labor was not controlled, and 3) the timing of epidural catheter placement in terms of cervical dilation was not described. Philipsen and Jensen (16) randomized 111 women (104 nulliparous) to receive either an epidural anesthetic (n = 57) or parenteral meperidine (n = 54). They did not find a statistically significant difference in the cesarean delivery rate between those who received an epidural anesthetic (17%) and those who did not (11%). However, they enrolled few patients and did not control for cervical dilation at the time of epidural catheter placement in order to reach a definitive conclusion. Thorp et al. (17), in 1993, published the results of the first prospective and randomized study suggesting that epidural analgesia increases the cesarean delivery rate. They randomized nulliparous women to receive either an epidural anesthetic (n = 48) or IV meperidine (n = 45). Originally, the authors planned to enroll 200 women, but they analyzed the data after 93 were enrolled. Based on these interim results, they decided it was unethical to continue the study. They found that the incidence of cesarean delivery was greater in the epidural group (16.7%) than in the nonepidural group (2.2%). They also found that all the cesarean deliveries in the epidural group were in women who received an anesthetic before 5-cm cervical dilation. They concluded that epidural analgesia significantly increases the cesarean delivery rate for dystocia and that this occurs when the epidural catheter is placed before 5-cm cervical dilation. Stopping the study based on their interim analysis was controversial. Their interim results were based on so few patients that if one additional woman in the nonepidural group had a cesarean delivery the results would no longer have reached statistical significance. One of Thorp et al.s (17) recommendations was that labor epidural analgesia should be delayed until 5-cm cervical dilation. Chestnut et al. (18) performed two studies, one with nulliparous women in spontaneous labor (18) and one with nulliparous women whose labor was induced with oxytocin (19). All women had an epidural catheter placed on request (between 3- and 5-cm cervical dilation). The women were then randomized to either receive local anesthetic at the time of epidural catheter placement (Early Group), or IV opioids until 5-cm cervical dilation after which epidural local anesthetic was administered (Late Group). Chestnut et al. (19) found no difference in the cesarean delivery rate between the two groups. This was the case both in women who were in spontaneous labor (10% Early Group versus 8% Late Group) and in those whose labor was induced (17% Early Group versus 19% Late Group). One cannot conclude from either of these studies (19,20) that epidural analgesia does not have an impact on the cesarean delivery rate, because there was no control group. However, the studies suggest that there is no benefit in delaying labor epidural anesthesia until 5-cm cervical dilation. Ramin et al. (20) randomized 1,330 women of mixed parity to receive either IV meperidine (n = 664) or an epidural anesthetic (n = 666). Of the 1,330 enrolled, 461 (35%) did not receive the treatment to which they were randomized, 232 from the epidural group and 229 from the IV meperidine group. All patients were enrolled when cervical dilation was between 3 and 5 cm, and all were managed with the active management of labor protocol. They found, with an intention-to-treat analysis, that there was a greater "operative delivery rate" in the epidural group (9%) than in the nonepidural group (5%). An "operative delivery" was defined as either a forcep-assisted vaginal delivery or cesarean delivery, and, therefore, one cannot draw any conclusions from this study about the relationship between epidural anesthesia and cesarean delivery rate. Sharma et al. (21), from the same medical center as Ramin, performed another prospective, randomized study, but attempted to decrease the number of women who crossed-over between groups. Women of mixed parity were randomized to receive either an epidural anesthetic (n = 315) or IV patient-controlled analgesia (PCA) with meperidine (n = 357). In the epidural group, 115 women did not comply with the protocol, and, in the PCA group, 98 did not comply. Most of these patients delivered too quickly, before they received any anesthetic. Only five women in the PCA group and eight in the epidural group changed group assignments. Using an intention-to-treat analysis, they did not find a difference in the cesarean delivery rate between the groups (epidural 4% versus PCA 5%). Applicability to other institutions is difficult, because all patients were in active labor and most did not have continuous fetal heart rate monitoring and were indigent. Those with continuous fetal heart rate monitoring (22), and nonindigent women (23) have greater cesarean delivery rates than their counterparts. Gambling et al. (24), also from the same medical center as Ramin, randomized women to receive IV meperidine (n = 607) or a combined spinal-epidural anesthetic with sufentanil (n = 616). The protocol was not followed in 471 women, many of whom crossed over to the other group. An intention-to-treat analysis demonstrated no difference in the cesarean delivery rate between the combined spinal-epidural group (10%) and the IV meperidine group (9%). Limitations of the study are the same as those described for Sharma et al.s (21) study, and there were many patients who did not comply with the protocol. Bofill et al. (25) randomized nulliparous women to receive IV butorphanol (n = 51) or labor epidural analgesia (n = 49). They had very strict criteria for labor management and only enrolled nulliparous women in spontaneous active labor whose cervix was dilated at least 4 cm. The authors stopped the study before completion, because they had difficulty enrolling patients. Using an intent-to-treat analysis, they were not able to find a difference in the cesarean delivery rate between the epidural group (8%) and the opioid group (6%). The study conclusions are limited because of the small number of patients in the study and the relatively large number (14%) of women who crossed over between groups. There are two recent meta-analyses of all the prospective, randomized studies of epidural analgesia and the cesarean delivery rate (27,28). Both concluded that regional anesthesia is not associated with an increase in the cesarean delivery rate for dystocia. Halpern et al. (26) analyzed the results from 10 prospective, randomized studies representing data on 2,369 patients, 1183 of whom received an epidural anesthetic and 1,186 of whom received parenteral opioids. The cesarean delivery rate in the epidural group was 8.2% and in the parenteral opioid group was 5.6%. Zhang et al. (27) analyzed the results from four prospective studies and four observational studies regarding the effect of epidural analgesia on the cesarean delivery rate. They found in the prospective and observational studies that epidural analgesia does not increase the risk for cesarean delivery. In addition to the studies previously described, there is other pertinent evidence to review. Three groups of investigators (2830) published the results of interventions made at their hospitals in an attempt to decrease the cesarean delivery rate. These changes included encouraging vaginal birth after cesarean delivery and changing to an active management of labor protocol. All three institutions were able to decrease their cesarean delivery rate but, at the same time, the rate of epidural analgesia increased. Goyert et al. (31) found that the individual obstetrician was an important determinant for cesarean delivery. Clark et al. (32) reviewed the data from their hospital to identify institutional and demographic influences on the cesarean delivery rate. They found a negative association between factors that might be perceived as a "high tech" approach to obstetric management and the cesarean delivery rate. These factors include: presence of obstetricians on staff rather than only family practitioners, full-time obstetric anesthesia coverage, large number of deliveries, urban setting, teaching hospital, having maternal-fetal medicine personnel on staff, and the existence of a newborn intensive care unit. Furthermore, it has been demonstrated that patients on public insurance appear to have lower cesarean delivery rates than private patients (23). In summary, the impact of epidural analgesia on the cesarean delivery rate is controversial. Even if there is an effect, it is probably minimal, relative to other factors known to increase the cesarean delivery rate (e.g., the individual obstetrician and labor management protocols). Known benefits of labor epidural analgesia make limiting its use based on current literature unjustified and potentially dangerous. The decrease in mortality for the parturient from the years 1979 through 1981, as compared with 1988 through 1990, appears to be related to the increase in the use of epidural analgesia and the decrease in the use of general anesthesia (1). A recent report by the American Society of Anesthesiologists Task Force on Obstetrical Anesthesia concluded that pain relief itself is enough of an indication to use epidural analgesia and that "cervical dilation at the time of epidural analgesia administration does not impact the outcome of labor" (33).
As described above, lumbar epidural analgesia is commonly used to manage labor pain. There are a number of problems with labor epidural analgesia that have prompted some to seek alternative techniques. The time from epidural catheter placement until the patient is comfortable is variable, and may take up to 30 min. Other disadvantages of labor epidural analgesia include maternal hypotension (34), inadequate analgesia in 15%20% of cases (35), and, even with very dilute local anesthetic solutions, motor block (36). Subarachnoid opioids offer rapid, intense analgesia with minimal changes in blood pressure (37) or motor function (38). The opioid, usually fentanyl or sufentanil, is commonly administered as part of a combined spinal-epidural (CSE) technique. After locating the epidural space in the usual manner, a long, small-gauge, pencil-point spinal needle is inserted through the epidural needle into the subarachnoid space. Fentanyl or sufentanil, either alone or in combination with local anesthetic, is administered through the spinal needle. The spinal needle is removed, and the epidural catheter is threaded for future use. Analgesia begins within 3 to 5 min and lasts 11.5 h (39,40). Palmer et al. (39) found that the ED50 of intrathecal fentanyl is 14 µg and that the duration of action increased to 89 min as the dose increased to 25 µg. Above 25 µg, the duration of action was not prolonged. Herman et al. (40) found that the ED50 for sufentanil was 2.6 µg and the ED95 was 8.9 µg. There are several advantages of the CSE technique. Collis et al. (41) found that fewer patients experienced motor block and more patients were satisfied when receiving the CSE technique versus the "standard" epidural technique of bupivacaine 0.25%. The greater satisfaction was related to the faster onset of action and less motor block (41). Grant et al. (37) found minimal changes in maternal blood pressure in nonlaboring term parturients after 25 µg of intrathecal fentanyl. This was true in women who received prehydration with 1,200 mL crystalloid solution and those who did not receive any prehydration. There have been several recent prospective studies looking at the effects of the CSE technique on the cesarean delivery rate. Nageotte et al. (42) randomized women to three groups: Group 1 received CSE with sufentanil 10 µg, Group 2 received the same technique and medication as those in Group 1 but were encouraged to ambulate, and Group 3 received epidural analgesia. They found no difference in the cesarean delivery rate among the three groups of patients. Gambling et al. (24) compared women who received CSE analgesia with those who received IV meperidine during labor, and they found no difference in the cesarean delivery rate between the two groups. There are some concerns about the CSE technique, most of which are only theoretical. There is no increased risk of subarachnoid catheter migration of the epidural catheter (44), and metallic particles are not produced as a result of passing one needle through another (45). Norris et al. (46) found that the incidence of postdural puncture headache is not increased with the CSE technique. An increase in end-tidal carbon dioxide has been reported in women who received subarachnoid sufentanil (47), but the risk of clinically significant respiratory depression is low (48). It is possible that the epidural catheter may not actually be in the epidural space after the CSE technique is performed, and this may not be detected until the analgesia from the intrathecal opioid has dissipated (12 h). If, during this period, the woman requires an emergent cesarean delivery, the catheter may fail, and the patient may require a general anesthetic. Norris et al. (49) found that the risk of failed epidural catheters was lower in women who received CSE analgesia than those who received epidural analgesia. However, it is prudent not to use the CSE technique in a woman who is a poor risk for general analgesia, e.g., one with a bad airway or obesity, because the epidural catheter cannot be immediately tested. Clarke et al. (50), in 1994, reported fetal bradycardia associated with uterine hypertonus after subarachnoid opioid injection. One proposed theory for increased uterine tone is related to the rapid decrease in maternal catecholamines associated with the onset of pain relief. With the decrease in circulating ß-adrenergic agonists, there is a predominance of alpha activity that leads to uterine contractions (51). Three retrospective studies showed no difference in the incidence of fetal heart rate abnormalities with CSE analgesia versus epidural analgesia (5254). A large retrospective review found no difference in the incidence of emergency cesarean delivery in 1,217 women who received CSE analgesia versus 1,140 who did not receive neuraxial analgesia (55). If hypertonus occurs, treatment should include subcutaneous terbutaline or IV nitroglycerin (56).
Breast feeding is widely recognized as the preferred means of neonatal nutrition (57,58). Difficulty in breast feeding in the early postpartum period is a common problem, but motivated mothers, even under adverse conditions (e.g., preterm twins), may achieve a 90% success rate (60). The effect of labor analgesia and anesthesia on subsequent breast feeding success has been the subject of much debate, but relatively little genuine sound research. One recent review article by Walker (60), a lactation consultant, attempted to find studies meeting four criteria: 1) use of breast feeding or any type of infant feeding as an outcome, 2) use of breast feeding assessment tools, 3) inclusion of a nonmedicated control group, and 4) assessment of infant behavior after 24 h. Walker (60) could not find any study that met this selection criteria. Interestingly, despite the absence of such literature, she concluded that epidural anesthesia has a negative impact on breast feeding success and suggested that "hospitals can avoid the use of epidural medications to help reduce the spending of scarce healthcare dollars, [but] daily follow-up from a breast feeding expert [should be] covered by insurance..." (60).
Breast Feeding After Cesarean Delivery Mathur et al. (62) confirmed that an early start of breast feeding is more successful. They found that all mothers who were breast feeding within 12 h of cesarean delivery were exclusively breast feeding their infants during that hospitalization, whereas only 5.8% of mothers who initiated breast feeding after 96 h were exclusively breast feeding during that hospitalization. Hirose et al. (63) randomized 2 groups of 15 patients who underwent a cesarean delivery under spinal anesthesia to receive either postoperative epidural analgesia with bupivacaine or IV analgesia. They found that mothers receiving epidural bupivacaine for 3 postoperative days experienced significantly lower pain scores and had more success with breast feeding and greater infant weight gain. In conclusion, it appears that early maternal-infant bonding leads to greater success in breast feeding (61,62) as does adequate postoperative pain control (63). Thus, epidural anesthesia is preferable to general anesthesia, and adequate postoperative analgesia is desirable.
Breast Feeding After Vaginal Delivery Halpern et al. (65) contacted patients by telephone 6 wk after delivery to determine if they were still breast feeding and then performed a chart review to determine the type of analgesia received during labor. They were not able to find a difference in breast feeding success between those who received an epidural anesthetic and those who did not. However, they did not control for the epidural medication used nor was there any assessment before 6 wk. In conclusion, although the type and amount of anesthetic drug administered during the peripartum period may affect breast feeding success rate, other factors, such as early maternal-baby bonding, appear to be of much greater importance. It seems wise to try to administer an anesthetic that allows for earliest possible maternal-infant contact, which would favor neuraxial anesthesia for both vaginal delivery and cesarean delivery.
Thermoregulation, in both adults and infants (66,67), is markedly impaired during general anesthesia, invariably leading to hypothermia (68). Sessler et al. (69) demonstrated a decrease in the thermoregulatory threshold for vasoconstriction in humans during halothane anesthesia. Desflurane, isoflurane, enflurane, and sevoflurane as well as nitrous oxide-fentanyl anesthesia also decrease the hypothermic threshold for vasoconstriction (68,70). Matsukawa et al. (71) found that redistribution of heat from the core to peripheral tissue accounted for 81% of the initial core temperature decrease. As the duration of general anesthesia increases, the decrease in core temperature slows and reaches a plateau. This is a result of the onset of thermoregulatory vasoconstriction. Epidural and spinal anesthesia also result in hypothermia caused by redistribution of heat from the core to the periphery (72). Because upper and lower extremities vasodilate during general anesthesia, but only the lower extremities vasodilate during regional anesthesia, the decrease in core temperature after regional epidural anesthesia is less than after general anesthesia (71). In contrast to the drop in core temperature that occurs during the first 3 h of epidural anesthesia provided for nonobstetric surgery, a rise in maternal temperature after labor epidural analgesia has been reported by three separate investigators (7375). All three studies demonstrated a small rise in maternal temperature after epidural analgesia administration of about 0.07°C/h. This was especially true in a warm environment (74). One of the more controversial studies was published by Lieberman et al. (76) who reported an association among epidural analgesia, maternal temperature greater than 100.4°F, and the need for neonatal sepsis evaluation and antibiotic treatment. Epidural analgesia was administered upon request and was not randomized. This led to selection bias, because women experiencing longer and more painful labors are more likely to request epidural analgesia and have an elevated temperature. Their finding of temperature elevation after epidural analgesia is consistent with other studies. However, their criteria for neonatal sepsis evaluation, a maternal temperature >100.4°F, is very conservative, and resulted in 25% of term newborn sepsis evaluations. Of the 416 infants evaluated and treated for sepsis, only 4 had documented sepsis. For comparison, at our hospital, the incidence of neonatal sepsis evaluation is 2% to 3%, and the rate of labor epidural analgesia is 85%. Lieberman et al.s (76) conclusions are therefore, at best, institution-specific. In another analysis of the same group of patients, Lieberman et al. (77) found that maternal temperature elevation is associated with cesarean delivery regardless of whether the mother had epidural analgesia. Furthermore, they concluded that the association of epidural analgesia with increased temperature may be one reason that epidural analgesia is associated with an increased cesarean delivery rate. Their conclusion is unfounded because, as in their previous study, the patients were not randomized to epidural versus IV analgesia. The association that they found was likely related to the inherent bias that women with longer and more painful labors are more likely to have an elevated temperature, have a cesarean delivery and request epidural analgesia than women with shorter labors. Philip et al. (78) recently reported the results of a prospective trial of women in labor randomized to receive epidural analgesia or PCA. They found that the incidence of maternal fever (temperature >38.0°C) was greater in women who received epidural analgesia, but the incidence of neonatal sepsis work-up was similar in both groups. At Philips institution, as at most hospitals, maternal temperature without other neonatal problems, is not an indication for a neonatal sepsis work-up. This article was accompanied by an editorial (79) that eloquently reviewed the differences between Lieberman et al.s (76) study and Philip et al.s (78) study. In summary, the increase in body temperature after induction of epidural analgesia for labor is minimal and of little clinical significance. It is not associated with maternal or neonatal infection. Obstetric and pediatric protocols for the use of antibiotics may need to be reviewed in the presence of a low grade temperature and prolonged epidural analgesia in the laboring patient.
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