EVIDENCE-BASED MEDICINE JOURNAL ARTICLE REVIEW
Kristen MacClenahan, MD and John Dacus, MD
Citation
Ohel G, Gonen R, Vaida S, Barak S, Gaitini L. Early
versus late initiation of epidural analgesia in labor: Does it
increase the risk of cesarean section? A randomized trial.
Am J Obstet Gynecol 2006;194:600-5.
Background
The issue of early epidural placement causing increased
incidence of cesarean section and operative vaginal
delivery has been a subject of longstanding debate. In
2002, ACOG recommended that “when feasible, obstetric
practitioners should delay the administration of epidural
analgesia in nulliparous women until cervical dilatation
reaches 4-5cm” due to a possible increased risk for
cesarean delivery if placed early.1 Since that time, several
randomized controlled trials have been published
demonstrating no increased risk of cesarean delivery with
early initiation of epidural analgesia.2-4 However, some
clinicians are still resistant to change. This study provides
further evidence in favor of early epidural anesthesia.
Hypothesis
The primary objective of this study was to determine
whether the administration of epidural analgesia during
early/latent labor (<4cm dilated) increased the incidence
of cesarean delivery. The secondary objectives involved
subjective measures of patient satisfaction with epidural
analgesia, i.e. sense of control, satisfaction with pain relief,
and satisfaction with timing of analgesia.
Methods
Design: Prospective, randomized, controlled, non-blinded
clinical trial. The randomization was stratified based on
spontaneous labor versus induction of labor. The baseline
cesarean rate among nulliparas at the study institution was
10%. The authors calculated that a total of 220 patients
were needed in each study group for an 80% power to
detect a doubling of the cesarean section rate assuming an
alpha of 0.05 using a 2 tailed test.
A total of 449 patients were enrolled: 279 in spontaneous
labor and 170 with induced labor. These patients were
then randomized into two groups: Group 1 (early epidural,
n=221) and Group 2 (late epidural, n=228). The data was
analyzed using the chi-square, student t test, Wilcoxon 2
sample test and logistic regression analysis.
Setting: The study was conducted in the labor and delivery
unit at Bnai Zion Medical Center in Haifa, Israel. The
epidurals were administered by anesthesiologists and
obstetric management performed by the obstetric team
which consisted of certified nurse midwives, residents,
staff obstetricians, and maternal-fetal medicine specialists.
Subjects: The patient population consisted of nulliparous
patients presenting to labor and delivery in either
spontaneous
labor
or
early
labor
with
augmentation/induction. All nulliparous patients that
requested epidural analgesia were invited to participate in
the study. A total of 449 patients were enrolled and all
were included in the analysis. Inclusion criteria were
nulliparity, >37 weeks gestation and established labor
(spontaneous or induced), at least 2 painful contractions in
10 minutes, cervix at > 80% effaced and < 3cm dilated.
Exclusion criteria were contraindications to epidural
analgesia, cervical dilatation > 3cm dilated, EFW >4000g,
medical complications (pre-eclampsia, diabetes) and
abnormal fetal heart rate tracing on admission.
Intervention: The primary intervention was early versus
late administration of epidural analgesia. Early
administration was defined as immediately following the
women’s request after enrollment in the study. Late
administration was defined as cervical dilatation of at least
4-5cm. The placement and administration of epidural
anesthesia was identical in each group, utilizing ropivacaine
and fentanyl. The study patients were followed from time
of enrollment through their postpartum hospitalization.
Outcomes: The primary outcome was incidence of
cesarean delivery. Delivery mode was recorded for each
patient. The need for cesarean section was determined by
the obstetric team according to maternal and fetal
indications. Failure to progress requiring both cesarean and
instrumental vaginal deliveries was defined as no change in
cervical dilatation for greater than 3 hours with epidural
analgesia and greater than 2 hours without.
The secondary outcomes of patient satisfaction with
analgesia were obtained by questionnaires. Pain at time of
randomization was evaluated using a standard visual analog
pain scale. Patient perception of control throughout the
labor process was evaluated using the Labour Agentry
Scale 24 hours after delivery. In addition, satisfaction was
determined using two additional questions 24 hours after
delivery:
1. “Following your particular experiences with the
timing of initiation of epidural analgesia, would
you prefer, next time, to be allocated to the other
study group? (yes, no, don’t care);”
Division of Maternal-Fetal Medicine / Department of Obstetrics & Gynecology
Greenville Hospital System University Medical Group
EVIDENCE-BASED MEDICINE JOURNAL ARTICLE REVIEW, CONTINUED
2. “Were you satisfied with the epidural analgesia?
(yes, no or partially satisfied).’”
Additional secondary outcomes assessed were incidence of
operative vaginal deliveries, neonatal outcomes, incidence
of maternal fever, meconium, and time from
randomization to full dilatation, and need for oxytocin
augmentation. Since the outcomes were all measured
during the hospitalization, follow up was complete for all
patients.
randomized. Both groups were similar at the initiation of
the trial with respect to demographics, BMI, initial cervical
dilatation, rupture of membranes, cervical effacement,
initial pain score, gestational age, and birth weight. The
groups were treated equally throughout the study course
except for the timing of epidural analgesia. The outcomes
measured were objectified and data analysis was completed
using intention to treat, including all patients. The only
source of possible bias which might affect validity was the
non-blinded nature of the study.
Results
Recommendation
No difference between rate of cesarean section (13% early,
11% late (p=0.77) and rate of instrumental vaginal delivery
(17% early, 19% late (p=0.63) was detected. A shorter
duration from time of randomization to full dilatation was
observed in the early group compared to the late group
(5.9 vs. 6.6 respectively (p=0.04)). In addition, no
difference in duration of second stage of labor, neonatal
outcomes, rate of maternal fever, or need for oxytocin
augmentation was found.
The results of this study are clinically useful. In major
labor and delivery suites, most patients elect to receive
epidural analgesia if it is readily available. Therefore, timing
of epidural placement is an issue that is addressed on a
daily basis. This study supports earlier investigations that
suggest that early placement of epidural is not associated
with a statistically significant increase in the incidence of
cesarean or operative delivery. Therefore, clinicians should
consider responding to requests for epidural analgesia
regardless of the stage of labor.
Patient preference to be placed in the early epidural group
for future deliveries was found to be significant
(p<0.0001); however, no difference with satisfaction of
analgesia once administered was appreciated.
Commentary
This study was not the first randomized controlled trial to
compare obstetric outcomes with timing of epidural
anesthesia. The first randomized trial conducted by
Chestnut et al in 1994 demonstrated no difference in time
to complete dilatation, incidence of cesarean delivery, or
need for operative vaginal delivery in nulliparous patients
both in spontaneous labor and those undergoing oxytocin
augmentation.1,2 A subsequent randomized controlled trial
published by Wong et al in 1995, compared early verses
late epidural in nulliparous patients and again confirmed
no difference in cesarean or operative delivery rates.4
Ohel’s study is only the third randomized trial since 1994
to readdress the issue of epidural timing and obstetric
outcomes.
This study met ethical criteria and was approved by the
local ethics committee at the participating study site. The
patients were enrolled after informed consent and they
were offered alternative analgesics while awaiting epidural
placement.
The methodology of this study was sound and the results
were valid. The design was a randomized controlled trial,
follow up was complete, all patients enrolled were
accounted for in the statistical analyses, and all patients
were analyzed in the groups to which they were
References
1. ACOG Practice Bulletin. Obstetric analgesia and
anesthesia. 2002; No 36:177-191.
2. Chestnut et al. Does early administration of
epidural analgesia affect obstetric outcome in
nulliparous women who are receiving intravenous
oxytocin? Anesthesiology 1994;80:1193-1200.
3. Chestnut et al. Does early administration of
epidural analgesia affect obstetric outcome in
nulliparous women who are in spontaneous labor?
Anesthesiology 1994;80:1201-1208.
4. Wong et al. The risk of cesarean delivery with
neuraxial analgesia given early versus late in labor.
N Eng J Med 2005;352:655-665.
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about therapy or prevention. What were the
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patients? JAMA 1994;271: 59-63.
8. Dans AL, Dans LF, Guyatt GH, Richardson S.
Users’ guides to the medical literature. How to
decide on the applicability of clinical trial results to
your patient. JAMA 1998;279:545-549.
Division of Maternal-Fetal Medicine / Department of Obstetrics & Gynecology
Greenville Hospital System University Medical Group