The effects of epidural analgesia on labor, maternal, and neonatal outcomes: A systematic review

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1 The effects of epidural analgesia on labor, maternal, and neonatal outcomes: A systematic review Barbara L. Leighton, MD, a and Stephen H. Halpern, MD b, c New York, NY, and Toronto, Ontario, Canada. Mothers given an epidural rather than parenteral opioid labor analgesia report less pain and are more satisfied with their pain relief. Analgesic method does not affect fetal oxygenation, neonatal ph, or 5-minute Apgar scores; however, neonates whose mothers received parenteral opioids require naloxone and have low 1-minute Apgar scores more frequently than do neonates whose mothers received epidural analgesia. Epidural labor analgesia does not affect the incidence of cesarean delivery, instrumented vaginal delivery for dystocia, or new-onset long-term back pain. Epidural analgesia is associated with longer second stage labor, more frequent oxytocin augmentation, hypotension, and maternal fever (particularly among women who shiver) but not with longer first stage labor. Analgesic method does not affect lactation success. Epidural use and urinary incontinence are associated immediately postpartum but not at 3 or 12 months. The mechanisms of these unintended effects need to be determined to improve epidural labor analgesia. ( 2002;186:S69-77.) Key words: Epidural analgesia, labor, obstetric anesthesia, cesarean delivery, opioid Epidural analgesia effectively relieves labor pain and is now chosen by many parturient women, particularly in the United States. 1-4 However, some authors are concerned that the beneficial effects of epidural analgesia may be offset by detrimental effects on labor progress, 4 to the newborn, 5 and to the mother. 6 Whether this is true has been a subject of debate for many years. Unfortunately, although numerous studies have been performed, the results are often contradictory. To determine whether epidural analgesia causes important side effects, we have performed this systematic review. We decided, a priori, that only randomized controlled trials (RCT) or, in the absence of randomized trials, high-quality prospective cohort (PC) studies would be included. Where appropriate, we combined the results with meta-analytic techniques. By using only the highest quality information available, we hope to avoid bias in our conclusions. Material and methods Literature review. We sought randomized controlled trials and prospective cohort studies in which epidural From the Department of Anesthesiology, a Weill Medical College of Cornell University, New York, NY, and the Departments of Anaesthesiology b and Obstetrics and Gynaecology, c University of Toronto, Ontario, Canada. This research was supported only by departmental funding. Reprint requests: Barbara L. Leighton, MD, 1901 Walnut St, Apt 1004, Philadelphia, PA bleigh@alumni.princeton.edu 2002, Mosby, Inc. All rights reserved /2002 $ /0/ doi: /mob analgesia was compared with parenteral opioids in labor. Cohort studies were used (1) only if no randomized trials were available for a particular outcome, and (2) only if the studies met the following criteria established by Margetts et al 7 to identify high-quality prospective cohort studies: the relationship of the sample to the population was defined, the response rate for those asked to participate was at least 60%, there were at least 50 patients in the inception cohort, the assessment method was clearly described, and data on at least 90% of the inception cohort patients were analyzed. 7 We searched for studies of the following topics: maternal comfort, operative delivery (cesarean or instrumented vaginal delivery), length of first stage labor, length of second stage labor, maternal temperature, neonatal cord ph, neonatal Apgar scores, long-term maternal back pain, breast-feeding success, and urinary incontinence. We expanded a previously described literature search, including 3 new topics (back pain, breast-feeding, and incontinence) and updating the search to March 7, Articles in the original and updated searches were retrieved from MEDLINE, EMBASE, and The Cochrane Library using the following medical subject heading terms: cesarean delivery; analgesia, epidural; analgesia, opioid; and analgesia, obstetrical. For outcomes not included in the original review, we searched using the following terms (text, alternate spellings, and key words): breast-feeding; anesthesia (or analgesia) and breast-feeding; epidural (or analgesia) and urinary incontinence; and epidural (or analgesia) and back pain. We updated our original hand search of the International Journal of Obstetric Anes- S69

2 S70 Leighton and Halpern May 2002 thesia from January 1998 to January We sought relevant articles in the bibliographies of recent review articles 8-10 and in our personal files. We also included published abstracts from January 1998 to March 2001 of the following meetings: the American Society of Anesthesiologists, the International Anesthesia Research Society, the Society for Obstetric Anesthesia and Perinatology, and the Society for Maternal Fetal Medicine (formerly the Society of Perinatal Obstetricians). In addition, the authors reviewed the abstracts of studies identified by the Maternity Center Association as potential candidates for inclusion in this systematic review. Quality of the trials. We assessed each peer-reviewed randomized trial for quality using the Jadad scale, a previously validated, reliable instrument. 11 Studies available only in abstract form were not rated for quality. The Jadad scale grades quality in 3 areas, for a maximum possible score of 5 points. Randomization and blinding methods each receive a grade between 0 and 2 points (0, inappropriate; 1, not described; and 2, appropriate). One point is given if the outcome of all enrolled study patients is described. Data analysis. Where appropriate, meta-analytic techniques (Metaview software, Revman 4.1, Cochrane Library, Oxford, England) were used to combine the results of randomized trials using the random effects model. Odds ratio (OR) and 95% confidence intervals (CI) were calculated for dichotomous data by using the methods of DerSimonian and Laird. 12 We tested for heterogeneity with the χ 2 test. The random effects weighted mean difference (WMD) and the 95% CI were calculated for continuous data. A statistical difference between groups was considered to occur if the pooled 95% CI did not include 1 for the OR or 0 for the WMD. An OR <1 or WMD <0 favored epidural over parenteral opioids. Where no randomized trials were available, prospective cohort studies were described but not combined. Results All retrieved studies were published in English between January 1, 1980, and February 1, ,13-24 Only healthy women with uneventful pregnancies were enrolled in these studies. The results of one trial were published as 2 separate articles, and one article describes 2 studies Randomized controlled trials. Since our last review, there have been 2 peer-reviewed published reports 10,13 and 2 abstracts 14,15 that compare epidural analgesia to parenteral opioids for labor pain. Determining whether epidural analgesia affects the incidence of long-term back pain was the primary goal of one published report. 10 One of the trials previously reported in abstract form has now been published as a peer-reviewed manuscript. 16 Maternal fever information is now available for one previously published trial. 25 Finally, additional information has become available on one of the trials that allows us to assess the cesarean delivery rate separately from the instrumented vaginal delivery rate. Ramin et al 20 originally reported an intent to treat analysis only for the indication of operative (ie, cesarean plus instrumented vaginal) delivery for dystocia (9% vs 5%; P =.008). The authors have now provided data on the overall cesarean delivery rate (6% vs 6%; P = NS). 26 A total of 14 randomized controlled trials that enrolled 4324 women met the inclusion criteria. Although all 14 trials reported the total cesarean delivery incidence with patients grouped by intent to treat, 3 trials also reported cesarean delivery rates among protocol-compliant patients. We analyzed only the intent to treat data for the outcome of cesarean delivery. Intent to treat data were analyzed for other outcomes when this information was available; otherwise, data on protocol-compliant patients were analyzed. Table I displays characteristics of the analyzed studies. In every trial, the obstetric providers knew the patient group assignment. In one study, consultation with a perinatologist unaware of group assignment occurred before a decision regarding cesarean delivery was made. 24 Jadad scores ranged from 1 to 3. Ten studies enrolled only nulliparous women, one study enrolled only multiparous women, and 3 studies enrolled women of mixed parity. Eight studies enrolled only spontaneously laboring women, 2 studies included women in both spontaneous and induced labor, and induction status was not described in 4 studies. Methodologic study details are described in Table II. Four studies do not report treatment crossovers. In 9 studies, some patients assigned to the parenteral opioid group received epidural analgesia in place of or in addition to parenteral opioids. In 6 studies, some patients assigned to the epidural group received either no analgesia or parenteral opioids only. Maternal outcomes. The incidence of cesarean delivery for any indication did not differ between patients randomized to receive parenteral opioids (7.7% [167/2163]) and patients randomized to receive epidural analgesia (8.0% [172/2161]) for labor pain relief (OR, 1.00; 95% CI, )(Figure). All of the studies except one 4 give similar results. We could not detect heterogeneity in the study results for this outcome (χ 2 ; P =.34). Similarly, there was no difference in the incidence of cesarean delivery for any indication if only high-quality studies (Jadad score = 3) were considered (parenteral opioid group, 8.9% [104/1164] vs epidural group, 9.0% [104/1156]; OR, 1.02; 95% CI, ; P = NS). Other maternal outcomes are displayed in Table III. Mothers receiving epidural analgesia had lower pain scores and were more satisfied with their analgesia. The total instrumented vaginal delivery rate was higher in the epidural group but the incidence of instrumented deliv-

3 Volume 186, Number 5 Leighton and Halpern S71 Table I. Characteristics of the analyzed studies Type of Country of Quality Population Induced Reference, year study origin score NP:MP labor included Comments Robinson, RCT UK 1 58:0 Unknown Robinson, RCT UK 1 0:35 Unknown Philipsen, ,90 19 RCT Denmark 3 104:7 Yes Thorp, RCT USA 3 93:0 No The trial was stopped early for ethical reasons. Ramin, RCT USA 2 693:637* No Parity and cervical dilatation at 484:385 request for analgesia were unbalanced between groups. Clark, RCT USA 3 318:0 No Both intent to treat and protocol compliant data were presented. Muir, RCT Canada Not rated 50:0 No Abstract Sharma, RCT USA 3 386:329 No Nikkola, RCT Finland 2 20:0 Unknown Primary outcome was the effect of analgesia on the neonate. Bofill, RCT USA 3 100:0 No The trial was stopped early because of slow recruitment. Sharma, RCT USA Not rated 342:0 No Abstract Loughnan, RCT UK 3 614:0 Unknown Muir, RCT Canada Not rated 185:0 No Multicentered trial Howell, RCT UK 3 369:0 Yes Primary outcome was back pain. Halpern, PC Canada Not rated 115:74 Unknown Viktrup, PC Denmark Not rated 208:0 Unknown Univariate analysis did not take into account confounding factors. NP, Nulliparous; MP, mulitparous; RCT, randomized controlled trial; PC, prospective cohort study; UK, United Kingdom, USA, United States of America. *Total number of enrolled patients, used to calculate the cesarean delivery incidence by intent to treat. Number of protocol-compliant patients, used for all other maternal and neonatal outcomes in this study. 20 ery for dystocia was not. Heterogeneity existed in the analyses of total instrumented vaginal delivery because some studies permitted elective forcep deliveries for resident training purposes. Heterogeneity also existed in the incidence of instrumented vaginal delivery for dystocia because different criteria for dystocia were used in the different studies. First stage labor length did not differ between the groups. The results for first stage labor length were heterogeneous because studies used differing definitions of first stage length. In addition, cervical examination frequency was standardized in only 3 of the 7 studies reporting this result. Second stage labor was longer in epidural group patients. The incidences of oxytocin initiation after analgesia, fever, and hypotension were higher in the epidural group. Neonatal outcomes. The incidence of poor 1-minute Apgar scores and the need for neonatal naloxone were higher in the parenteral opioid group (Table IV). The incidences of fetal heart rate abnormalities/intrapartum meconium, poor 5-minute Apgar scores, and low umbilical artery ph did not differ between the groups. We could not detect heterogeneity in these study results. Prospective cohort trials. No randomized controlled trials were available for 2 outcomes: breast-feeding success and urinary incontinence. One qualifying prospective cohort study was available for each of these outcomes (Table II). 27,28 The intrapartum analgesic method used did not affect lactation success at 6 weeks. 27 Urinary incontinence was more frequent among women who chose epidural analgesia in the immediate postpartum period (27% vs 13%; P =.05) but not at 3 months (16% vs 4%) or 1 year (7% vs 3%) postpartum. 28 Comment Meta-analysis of the randomized controlled trials shows that laboring women receiving epidural analgesia rather than parenteral opioids are more comfortable during the first and second stage labor and are more satisfied with their analgesia. There is no difference in the cesarean delivery rate (OR, 1.00; 95% CI, ). First stage labor length is slightly, but not significantly, longer in the epidural group. It is possible, however, that epidural analgesia affects first stage labor dynamics, because oxytocin is initiated much more frequently after epidural than after parenteral opioid analgesia. Alternatively, obstetricians who were aware of the patient group assignments may have used oxytocin augmentation more frequently in patients who receive epidural analgesia. Second stage labor is significantly longer in patients who receive epidural analgesia (WMD, 15 min; 95% CI, 9-22). The total incidence of instrumented vaginal delivery is higher in the epidural group but the incidence of instrumented delivery for dystocia is not. Elective forceps deliveries performed for resident training purposes contributed to this discrepancy. 24 The epidural group had higher rates of

4 S72 Leighton and Halpern May 2002 Table II. Methodologic details of analyzed studies Study Labor protocol Criteria for operative intervention Analgesic protocol, parenteral opioid Randomized controlled trials Robinson, Unknown Unknown Meperidine 150 mg + perphenazine 5 mg IM (both studies) q 4 h prn supplemented by 50% N 2 O and methoxyflurane 0.35% prn. Philipsen, ,19 Unknown Unknown Meperidine 75 mg IM prn supplemented by N 2 O 50% prn. Thorp EFM for all patients. Unknown Meperidine 75 mg + promethazine 25 mg No elective instrumented IV q 90 min as needed. vaginal deliveries. Dystocia diagnosed only after documentation of adequate labor by internal uterine pressure monitor. Fetal distress diagnosed by persistent ominous fetal heart rate tracing or scalp ph. Ramin, Protocol in labor floor manual. Criteria for low Meperidine 50 mg IV q 4 h prn + Early amniotomy, IUPC EFM, forceps, not for promethazine 25 mg with the first dose. oxytocin, no elective forceps. CD. Epidural if inadequate pain relief. Muir, Strict definitions for diagnosis Unknown IV patient controlled analgesia meperidine and management of labor. 1 mg/kg loading dose. Clark, Active management of labor Obstetrical reasons IV meperidine mg q 90 min as needed. Nikkola, Unknown Unknown IV patient controlled analgesia fentanyl, stopped in second stage. Sharma, Protocol in labor floor manual. Criteria for low Meperidine 50 mg plus promethazine 25 mg Early amniotomy, electronic forceps, not for CD. followed by meperidine IV PCA. fetal monitoring, oxytocin, no elective forceps. Bofill, Active management of labor. CD decision made Butorphanol 1-2 mg IV Criteria for oxytocin by a perinatologist q 1-2 hr as needed. augmentation. blinded to patients analgesia assignment. 50/100 patients had instrumented vaginal deliveries for resident training. Sharma, Labor managed in a Not stated. Meperidine via IV PCA. codified manner. Loughnan, Active management of labor. Decision to do an Meperidine IM q 2 hr prn to a operative delivery was maximum of 300 mg. made by midwifery and medical staff not involved with the study. Muir, Labor managed by protocol. Predefined Intravenous patient controlled analgesia using fentanyl. Howell, Not stated Not stated Meperidine mg repeated according to midwifery practice. Prospective Cohort Studies Halpern, Not standardized Not standardized Intramuscular nalbuphine, meperidine, or morphine at the discretion of the attending obstetrician. Viktrup, Not standardized Not standardized Not stated IM, Intramuscular; IV, intravenous; q, every; prn, as required; IUPC, intrauterine pressure catheter; EFM, electronic fetal monitoring; CD, cesarean delivery; PCA, patient-controlled analgesia.

5 Volume 186, Number 5 Leighton and Halpern S73 Analgesic protocol epidural Randomized controlled trials Bupivacaine 0.5% 5-10 ml bolus doses as needed, no infusion. None reported Crossover rate Test dose 1% lidocaine with epinephrine. Bolus doses of 0.375% None reported bupivacaine, no infusion. No topups in second stage. N 2 O 50% prn. 0.25% bupivacaine bolus, bupivacaine 0.125% infusion adjusted 1/48 patients assigned to the epidural group to maintain a T 10 level. Infusions were continued through did not receive an epidural. second stage labor if adequate progress was made. 1/45 patients assigned to the parenteral opioid group also received an epidural. Bupivacaine 0.25% bolus, bupivacaine, 0.125% with 2 µg/ml fentanyl infusion to maintain a T 8 level. Bupivacaine 0.125%/epinephrine/ meperidine bolus, bupivacaine 0.125%/epinephrine/meperidine patient controlled epidural analgesia Lidocaine 1% test dose, bupivacaine 0.25%/50 µg fentanyl bolus, bupivacaine 0.125%/fentanyl 1 µg/ml infusion, adjusted to maintain a T l0 level. 103/666 in the parenteral opioid group also received an epidural. 232/664 randomized to receive an epidural received no medication. 11/22 in the parenteral opioid group also received an epidural. 84/162 in the parenteral opioid group also received an epidural. 5/156 in the epidural group received IV opioids (no epidural). 4 received no medication. Bupivacaine 0.5% 6 ml followed by 4 ml boluses prn, no infusion, 4/10 in the parenteral opioid group also received epidural not routinely given in second stage. an epidural. Bupivacaine 0.25% bolus, infusion bupivacaine 0.125% with Of 358 women assigned to the meperidine group, 2 µg/ml fentanyl to maintain a T 10 level. 93 did not receive any medication and 5 received an epidural after receiving meperidine. Of 357 women assigned to the epidural group, 115 received no medication and 8 received only parenteral opioids. Bupivacaine 0.25%/fentanyl µg bolus, infusion of bupivacaine 0.125%/fentanyl 1.5 µg/ml. 2/49 in the epidural group received no medication. 12/51 in the parenteral opioid group received opioid plus an epidural. Bupivacaine 0.25% with fentanyl; bupivacaine 0.06%/fentanyl 7% of women randomized to the meperidine 2 µg/ml patient controlled epidural and 5 ml/hr group received epidural analgesia. background infusion. Bupivacaine 0.25% ml followed by bupivacaine Of the 304 women who were randomized to epidural, 0.125% at ml/hr until the second stage. 244 received an epidural, 13 received meperidine and an epidural, 47 received either meperidine or Entonox. Of the 310 women randomized to meperidine, 132 received meperidine, 89 received an epidural, 86 received an epidural and meperidine, and 3 received Entonox. Epidural patient controlled 0.08% bupivacaine with Unknown 1.67 µg/ml fentanyl. Bupivacaine 0.25% 10 ml initially, bolus doses of 5 to 10 ml 61/184 women in the epidural group did not receive bupivacaine 0.25% prn. an epidural. 52/185 women in the nonepidural group received an epidural. Prospective Cohort Studies Initiated with either a combined spinal/epidural NA (bupivacaine/fentanyl) or an epidural using 0.25% bupivacaine or 1.5% lidocaine. Maintained with 8-12 ml/hr bupivacaine 0.08% mixed with either fentanyl 2 µg/ml or sufentanil 0.6 µg/ml. Bupivacaine 0.375% bolus doses prn. NA

6 S74 Leighton and Halpern May 2002 Figure. Overall cesarean delivery rate for each randomized study. Individual and pooled (total) odds ratios (OR) and 95% confidence intervals (CI) are shown. Odds ratios were not estimable for the 3 studies with no cesarean deliveries. Each box is centered at the point estimate of the OR and is proportional in size to the number of patients in the study. The bars indicate 95% CIs. The center of the diamond represents the point estimate of the pooled OR, and the length of the diamond is proportional to the pooled 95% CI. hypotension and maternal temperature >38 C; the incidence of nausea did not differ between the groups. Neonatal outcome measures either favor epidural analgesia or do not differ between the groups. Individual studies show no association between epidural analgesia and longterm back pain or breast-feeding problems; epidural use is associated with urinary incontinence in the immediate postpartum period but not at 3 or 12 months. The results of this systematic review are consistent with those of the authors last systematic review of the subject, published in The present work includes more studies (14 vs 10), more patients (4324 vs 2369), and 3 previously unreviewed topics (back pain, breast-feeding, and urinary incontinence). The nonsignificant trend toward an increased total cesarean delivery rate seen in the previous systemic review (OR, 1.50; 95% CI, ) is not seen in the present work (OR, 1.00; 95% CI, ). The heterogeneity seen in the previous review was the result of one small study with a very high cesarean delivery rate among epidural group patients. 4 This heterogeneity is not significant in the current larger review. First stage labor length, which differed significantly in our previous analysis, no longer differs because the 4 added studies report little difference for this outcome. Apgar score <7 at 5 minutes and low umbilical artery ph differed significantly in the previous but not the present work. Cesarean delivery is clearly not associated with epidural analgesia in these randomized trials. Similar results were obtained in a systematic review of the epidemiologic studies comparing cesarean delivery rates before and after large changes in epidural utilization. 9 Nine studies that enrolled 37,753 women were analyzed; the net change in the cesarean delivery rate was 0.67% (95% CI, 2.0%-0.74%). 9 However, unrandomized trials in which patients chose their method of analgesia have found a strong association between epidural use and cesarean delivery. 29, 30 We hypothesize that unknown, underlying factors lead both to increased labor pain and to an increased risk of cesarean delivery. This hypothesis is supported by subgroup analysis of 3 of the epidemiologic studies In each study, the overall cesarean delivery rate did not change as epidural usage increased. However, when epidurals were freely available, women who chose epidural analgesia had a higher cesarean delivery rate than other parturient women in the studies by Fogel et al (8% vs 1%), Lyon et al (8% vs 1%), and Gribble and Meier (11% vs 3%) Epidural analgesia is associated with a 15-minute increase in second stage labor duration. Although the difference in first stage duration is not significant, oxytocin augmentation occurs more frequently in epidural group patients. More research needs to be done to determine how epidural analgesia affects labor speed. Both initial and first stage cervical dilation are faster in nulliparous women receiving combined spinal epidural analgesia with intrathecal sufentanil bupivacaine rather than epidural analgesia with bupivacaine fentanyl. 34 It is possible that epidural analgesia lengthens labor by changing the uterine sympathetic

7 Volume 186, Number 5 Leighton and Halpern S75 Table III. Other maternal outcomes Studies Epidural Opioid OR or WMD Outcome included n/n or N n/n or N (95% CI) P value Instrumented vaginal delivery* 4,10,13,15-18,20, / / ( ) <.05 Instrumented vaginal delivery 18,20,24 39/538 23/ ( ) NS for dystocia* Labor length, first stage 4,10,13,16,17,23, min ( 8.0 to 60) NS Labor length, second stage 4,10,13,16,17,18,23, min (9-22) <.05 Oxytocin postanalgesia* 4,23 99/282 49/ ( ) <.05 Fever (>38.0 C)* 15,20,23 212/845 49/ ( ) <.001 Hypotension* 20,23,24 312/839 1/ ( ) <.001 Nausea* /417 27/ ( ) NS Pain, first stage 4,16,17,19,20,23, mm ( 42 to 38) <.0001 Pain, second stage 4,16,17,19, mm ( 38 to 21) <.001 Satisfaction* 10,17,19,20,22,23 128/ / ( ) <.001 Mid back pain at 3 mo 10 36/162 30/ ( ) NS Low back pain at 3 mo 10 57/162 51/ ( ) NS Mid back pain at 12 mo 10 27/166 25/ ( ) NS Low back pain at 12 mo 10 58/166 43/ ( ) NS *Dichotomous data are shown as OR and 95% CI by using a random effects model. An OR of <1 favors epidural analgesia. n = the number of events, N = the total number of patients in the analysis. Continuous data are shown as weighted mean difference (WMD) and 95% confidence interval using a random effects model. Negative numbers favor epidural analgesia. N = the total number of patients in the analysis. Visual analog pain scores use a 100-mm scale. Table IV. Neonatal outcomes Studies Epidural Opioid OR or WMD Outcome included n/n or N n/n or N (95% CI) P value Fetal heart rate abnormalities 4,10,16,23 115/ / ( ) NS or intrapartum meconium* 1-min Apgar score <7* 4,16,20,22,23 39/ / ( ) <.05 5-min Apgar score <7* 4,10,16,18, / / ( ) NS Low umbilical artery ph* 4,16, / / ( ) NS Severe asphyxia: 18,20,22,23 2/857 2/ ( ) NS umbilical artery ph <6.99* Need for naloxone in the newborn* 15, /587 24/ ( ) <.01 Continuous data are shown as weighted mean difference and 95% CI by using a random effects model. Negative numbers favor epidural analgesia. N = the total number of patients in the analysis. Low umbilical artery ph was defined as <7.15 in studies 4, 16, and 21 and <7.20 in studies 20, 22, and 23. *Dichotomous data are shown as OR and 95% CI by using a random effects model. An OR of <1 favors epidural analgesia. n = the number of events, N = the total number of patients in the analysis. parasympathetic balance. Patients in whom labor is induced and who receive lumbar sympathetic nerve blocks in addition to epidural analgesia have shorter latent and second stage labors than patients who receive epidural analgesia alone. 35 Labor speed differences may also be partly pharmacologic. In the randomized trials in this systematic review, 93% of the control patients received intramuscular or intravenous meperidine (plus other drugs), whereas 100% of the epidural patients received bupivacaine (plus other drugs). Meperidine may speed or bupivacaine may slow cervical dilation, because the initial cervical dilation rate is 0.9 cm/hr in patients in whom labor is induced who receive epidural meperidine compared with 0.4 cm per hour in patients who receive epidural bupivacaine labor analgesia. 36 Maternal fever (intrapartum temperature >38 C) is associated with epidural labor analgesia in this meta-analysis and in 2 large retrospective studies. 5,37 However, whether neonatal sepsis workups (SWU) are triggered by these fevers depends on the SWU protocols of individual hospitals. Brigham and Women s Hospital, Boston, Mass, uses maternal temperature >38 C as a trigger for neonatal SWU; the incidence of neonatal SWU (but not the incidence of neonatal sepsis) is higher among women who receive epidural analgesia. 5 In contrast, Magee-Women s Hospital, Pittsburgh, Penn, uses neonatal temperature at 6 hours as a trigger, and the incidence of neonatal SWU is not increased in epidural group patients. 37 For study design reasons, the maternal temperature effects of epidural drug administration cannot be deduced from this systematic review. The control group in all 3 studies reporting maternal fever results received intravenous meperidine. All opioids suppress shivering by decreasing the core temperature at which shivering starts, but meperidine depresses the shivering threshold twice as much as other, equipotent opioids. 38 The observed differences in

8 S76 Leighton and Halpern May 2002 maternal body temperature may be related more to hypothermic effects of meperidine than to hyperthermic effects of epidural analgesia. More research should be done, particularly to determine why some normothermic women shiver after receiving epidural analgesia. 39 Maternal rectal temperature rises quickly in epidurally anesthetized parturient women who shiver but changes minimally in epidurally anesthetized parturient women who do not shiver. 40 Neonatal outcome is generally better with epidural analgesia than with parenteral opioid labor analgesia. This finding is probably dose-related. The more recent randomized trials used patient-controlled intravenous opioids in the nonepidural group, and some patients may have self-administered fairly large opioid doses. Back pain was not associated with epidural analgesia in the one randomized controlled trial that evaluated this outcome. Two prospective cohort studies also found no association between epidural use and back pain. Breen et al 41 enrolled 1185 women at delivery and surveyed them 2 months later. The incidence of back pain in women using and not using epidural analgesia did not differ (44% vs 45%). Macarthur et al 42, 43 prospectively followed 164 women who did and 165 women who did not receive epidural analgesia. The epidural group had more back pain on day 1 (53% vs 43%) but not on day 7, week 6, or at 1 year. Epidural use did not affect breast-feeding initiation or maintenance. A large (2275 patients) retrospective study confirms these results. 44 It is not surprising that epidural analgesia promotes breast-feeding, because it is well known that intrapartum opioids, particularly meperidine, delay the initiation of neonatal sucking behavior Urinary incontinence was more frequent in patients who receive epidural analgesia, but only in the immediate postpartum period. 28 There was a statistically significant association between second stage labor duration and new-onset urinary incontinence. 28 It is likely that common underlying factors lead both to requests for epidural analgesia and incontinence. A study linking information in 3 Swedish registries found that incontinence surgery was associated with vaginal delivery, high maternal body mass index, high infant birth weight, parity, and epidural usage. 48 Pudendal nerve damage was associated with multiparity, forceps delivery, increased second stage duration, and high infant birth weight, but not with epidural use in another study. 49 Thus, both forceps delivery and high infant birth weight, which increase maternal pain, are associated with incontinence. In conclusion, epidural analgesia provides a versatile method of administering effective and satisfactory pain relief to parturient women. The technique should not be considered as a single entity, because the type and dose of epidural medication can be altered as needed. Although childbirth has become much safer for mother and neonate, there is still room for improvement. Existing evidence suggests that women should not avoid epidural analgesia for fear of neonatal harm, breastfeeding difficulties, cesarean delivery, long-term back pain, or long-term urinary incontinence. Epidural analgesia may alter the dynamics of labor and maternal temperature regulation. These topics should be explored with appropriately designed, randomized, and multidisciplinary studies. REFERENCES 1. Gibbs CP, Krisher J, Peckham BM, Sharp H, Kirschbaum TH. Obstetric anesthesia: a national survey. Anesthesiology 1986; 65: Hawkins JL, Gibbs CP, Orleans M, Martin-Salvaj G, Beaty B. Obstetric anesthesia work force survey, 1981 versus Anesthesiology 1997;87: Halpern SH, Leighton BL, Ohlsson A, Barrett JFR, Rice A. Effect of epidural vs. parenteral opioid analgesia on the progress of labor. JAMA 1998;280: Thorp JA, Hu DH, Albin RM, McNitt J, Meyer BA, Cohen GR, et al. The effect of intrapartum epidural analgesia on nulliparous labor: a randomized, controlled, prospective trial. 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