Introduction
In 1847, only months after the first demonstration of anesthesia, James Simpson, an obstetrician, administered ether to a woman in labor for childbirth. He was quite impressed with the analgesia the new drug induced, as was his patient. However, his journal notes on the case indicated his concern over the possible adverse effects of anesthesia on labor and delivery. “It will be necessary to ascertain anesthesia’s precise effect, both upon the action of the uterus and on the assistant abdominal muscles; its influence, if any, upon the child; whether it has a tendency to hemorrhage or other complications.”
Thus began, more than a century and a half ago, perhaps the longest-lived controversy in the history of obstetric anesthesia, one that continues to this day in both academic and lay circles.
Options
The modern debate has centered on several main issues:
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Does regional analgesia for labor affect the length of labor or the rate of cervical dilation? In particular, does the timing of initiation of epidural analgesia play a role?
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Does regional labor analgesia increase the risk of instrumental vaginal delivery?
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Does regional labor analgesia increase the risk of cesarean delivery?
No definitive study has adequately addressed any of these questions, and methodologic problems have plagued all available evidence. The principal difficulty is that risk factors for dysfunctional labor also predispose a woman to request an epidural. This chapter will review the available literature, focusing on randomized controlled trials (RCTs) but considering other forms of evidence, and will emphasize the different conclusions reached by observational and prospective randomized designs.
Evidence
Evidence Regarding Rate of Cervical Dilation and Timing of Initiation
Conventional wisdom holds that if started too early in labor (during the latent phase), epidural analgesia may markedly slow or even arrest the progress of labor. Amazingly, this widely accepted clinical dogma has never been proved in carefully performed studies. Its origin can be traced to early case series of caudal or epidural anesthesia for labor, which probably resulted in dense sacral as well as lumbar blocks. In these uncontrolled reports, although some women in whom blocks were initiated very early may not have progressed through labor, it is unclear whether they would have progressed more quickly without the block.
Some nonrandomized studies have found an association between earlier epidural placement and dystocia. Thorp and colleagues compared various groups of nulliparous women defined by their early cervical dilation rate, their cervical dilation at the time of initiation of analgesia, and the choice of epidural or alternative analgesia. Among women with dilation less than 5 cm and a dilation rate less than 1 cm/hr, epidural analgesia was associated with a sixfold increase in cesarean delivery for dystocia. Other comparisons demonstrated smaller relative risks or no difference. In a secondary analysis of the same group’s randomized trial, the increased risk of cesarean delivery was greatest in women requesting analgesia earlier, although women were not randomly assigned to dilation at time of initiation of analgesia. Using a case-control methodology, Malone and colleagues identified epidural initiation at less than 2 cm dilation as a significant risk factor for prolonged nulliparous labor (odds ratio [OR], 42.7). In a sophisticated observational study using a variant of multivariate regression (propensity score analysis) to control for multiple simultaneous confounders, Lieberman and colleagues identified both cervical dilation less than 5 cm and station less than 0 at the time of epidural initiation as strong risk factors for cesarean delivery.
Evidence from RCTs has failed to confirm this finding ( Table 66-1 ). Chestnut and colleagues randomly assigned women requesting epidural analgesia to early or late groups (approximately 4 and 5 cm dilation, respectively). No differences in labor outcome were seen in either spontaneous labors or induced labors. However, the early and late groups in these studies were not markedly different in their cervical dilation at the time of epidural placement. Five more recent trials randomly assigned women to early epidural placement or opioids until later in labor or to intrathecal opioids followed by later epidural initiation. In each case, progress through the first stage of labor was either equivalent or faster in the early group than in the later group. No differences in second-stage duration or mode of delivery were found in any of the trials. Two meta-analyses of the RCTs, one performed before and one after the extremely large trial by Wang and colleagues, found no difference in the mode of delivery between early and later epidural initiation. The difference between the RCTs and the retrospective studies may be due to selection bias, in that women requesting analgesia earlier in labor may be experiencing pain due to anatomic or physiologic factors predisposing them to dystocia.
| Cervical Dilation in Centimeters ( N ) | Results | |||||
|---|---|---|---|---|---|---|
| Author, Year | Early | Late | Outcome | Early | Late | p |
| Chestnut, 1994 * | 4 (172) | 5 (162) | First stage (min) | 329 | 359 | NS |
| Second stage (min) | 85 | 88 | NS | |||
| CD (%) | 10 | 8 | NS | |||
| IVD (%) | 37 | 43 | NS | |||
| Chestnut, 1994 † | 3.5 (74) | 5 (75) | First stage (min) | 318 | 273 | NS |
| Second stage (min) | 91 | 77 | NS | |||
| CD (%) | 18 | 49 | NS | |||
| IVD (%) | 43 | 19 | NS | |||
| Luxman, 1998 | 2.5 (30) | 4.5 (30) | First stage (min) | 342 | 317 | NS |
| Second stage (min) | 41 | 38 | NS | |||
| CD (%) | 7 | 10 | NS | |||
| IVD (%) | 13 | 17 | NS | |||
| Wong, 2005 ‡ | <4 (366) | >4 (362) | First stage (min) | 295 | 385 | <0.001 |
| Second stage (min) | 71 | 82 | 0.67 | |||
| CD (%) | 18 | 21 | 0.31 | |||
| IVD (%) | 20 | 16 | 0.13 | |||
| Ohel, 2006 | 2.4 (221) | 4.6 (228) | First stage (min) | 354 | 396 | 0.04 |
| Second stage (min) | 95 | 105 | 0.12 | |||
| CD (%) | 13 | 11 | 0.77 | |||
| IVD (%) | 17 | 19 | 0.63 | |||
| Wong, 2009 § | 2 (406) | 4 (400) | Labor duration (min) | 528 | 569 | 0.047 |
| Second stage (min) | 89 | 90 | 0.56 | |||
| CD (%) | 33 | 32 | 0.65 | |||
| IVD (%) | 14 | 15 | 0.63 | |||
| Wang, 2009 | 1.6 (6394) | 5.1 (6399) | Latent phase (min) | 479 | 485 | 0.22 |
| Active phase (min) | 111 | 128 | 0.68 | |||
| Second stage (min) | 63 | 67 | 0.87 | |||
| CD (%) | 23 | 23 | 0.51 | |||
| IVD (%) | 12 | 13 | 0.10 | |||
* Spontaneous labor; cervical dilation given as median.
† Oxytocin-receiving subjects; cervical dilation given as median.
‡ Spontaneous labor; subjects randomly assigned at <4 cm to intrathecal fentanyl 25 mcg or intramuscular + intravenous hydromorphone; all subjects received epidural analgesia at second request for analgesia (systemic group) or >4 cm or at third request for analgesia (intrathecal group). Median cervical dilation at first request was 2 cm in both groups, but cervical examination at initiation of epidural analgesia in late group was not reported.
§ Nulliparas undergoing induction of labor, with cervical dilation given as median; analgesic protocol similar to Wong 2005. Total labor duration, but not first stage duration, was reported.
The effect of epidural analgesia on cervical dilation in established labor is probably minimal. Some earlier retrospective studies finding slower cervical dilation were probably hampered by selection bias. Meta-analyses of randomized trials of epidural analgesia versus opioid analgesia have concluded that the first stage of labor is not prolonged by epidural analgesia.
Evidence Concerning Risk of Instrumental Vaginal Delivery
The incidence of instrumental vaginal delivery may be increased by epidural analgesia, although this practice varies tremendously between obstetricians and hospitals. Table 66-2 shows the results of 21 randomized trials, published in English as full articles, comparing epidural analgesia with systemic opioids. Seven of the trials found a significant difference in rates. However, the overall use of forceps varied from 0% to 55% in the opioid groups and from 2% to 80% in the epidural groups, indicating substantial variation in practice style. Indeed, meta-analysis of randomized trials has found the total instrumental delivery rate to be 1.38 to 2.19 times more likely in patients receiving epidural analgesia but with very broad confidence intervals indicative of the variation between studies. Moreover, there is strong evidence that many instrumental deliveries in epidural patients are done for reasons other than dystocia, perhaps for teaching purposes. Indeed, two meta-analyses concluded that instrumental delivery for the indication of dystocia was not increased by epidural analgesia, and another concluded “non-elective” instrumental delivery was likely not increased (OR, 1.56; 95% CI, 0.99 to 2.46).
| Rate of Instrumental Vaginal Delivery * | Rate of Cesarean Delivery for Dystocia † | ||||||
|---|---|---|---|---|---|---|---|
| Author, Year | Parity | Epidural Group | Opioid Group | p | Epidural Group | Opioid Group | p |
| Robinson, 1980 | Nulliparas Mulitparas | 17/28 (51%) 5/17 (30%) | 8/30 (27%) 1/18 (6%) | <0.02 NS | 0 | 0 | — |
| Philipsen, 1989 | Nulliparas | 1/57 (2%) | 0/54 (0%) | NS | 10/57 (17%) | 6/54 (11%) | NS |
| Thorp, 1993 | Nulliparas | 4/48 (8.3%) | 3/45 (6.7%) | NS | 8/48 (16.7%) | 1/45 (2.2%) | <0.05 |
| Ramin, 1995 ‡ | Mixed | 41/432 (10%) | 13/437 (3%) | <0.0001 | 43/664 (6%) | 37/666 (6%) | NS |
| Bofill, 1997 | Nulliparas | 39/49 (80%) | 28/51 (55%) | 0.004 | 4/49 (4%) | 3/51 (3%) | NS |
| Sharma, 1997 | Mixed | 26/358 (7%) | 15/357 (4%) | NS | 13/358 (4%) | 16/357 (5%) | NS |
| Clark, 1998 | Nulliparas | 24/156 (15%) | 20/162 (12%) | NS | 15/156 (9.6%) | 22/162 (14%) | NS |
| Gambling, 1998 § | Mixed | 51/616 (8%) | 34/607 (6%) | 0.08 | 39/616 (6%) | 34/607 (6%) | NS |
| Nulliparas | 37/336 (13%) | 32/314 (13%) | NS | 30/336 (10%) | 25/314 (9%) | NS | |
| Loughnan, 2000 | Nulliparas | 88/304 (29%) | 81/310 (26%) | NS | 36/304 (12%) | 40/310 (13%) | NS |
| Howell, 2001 | Nulliparas | 55/184 (30%) | 36/185 (19%) | 0.03 | 13/184 (7%) | 17/185 (9%) | NS |
| Lucas, 2001 ‖ | Mixed | 51/372 (14%) | 27/366 (7%) | 0.005 | 46/372 (12%) | 54/366 (15%) | NS |
| Dickinson, 2002 ¶ | Nulliparas | 169/493 (34%) | 148/499 (30%) | NS | 85/493 (17%) | 71/499 (14%) | NS |
| Sharma, 2002 | Nulliparas | 26/226 (12%) | 7/233 (3%) | <0.001 | 13/226 (6%) | 17/233 (7%) | NS |
| Head, 2002 ‖ | Mixed | 3/56 (5%) | 3/60 (5%) | NS | 7/53 (13%) | 6/52 (12%) | NS |
| Jain, 2003 | Nulliparas | 12/43 (28%) | 8/83 (10%) | <0.01 | 9/45 (20%) | 12/83 (14%) | NS |
| Long, 2003 | Mixed | 1/30 (3%) | 6/50 (12%) | NS | |||
| Halpern, 2004 | Nulliparas | 36/124 (29%) | 25/118 (21%) | NS | 6/124 (5%) | 10/118 (5%) | NS |
| Nafisi, 2006 # | Nulliparous | 4/197 (2%) | 4/198 (2%) | NS | 8/197 (4%) | 8/198 (4%) | NS |
| Evron, 2008 | Mixed | 9/148 (6%) | 1/44 (2%) | NS | 19/148 (13%) | 4/44 (9%) | NS |
| Volmanen, 2008 | Mixed | 1/21 (5%) | 4/24 (17%) | NS | 1/21 (5%) | 1/24 (5%) | NS |
| El-Kerdawy, 2010 ‖ | Mixed | 3/15 (20%) | 0/15 (0%) | NS | 4/15 (27%) | 3/15 (20%) | NS |
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