Intermittent Epidural Bolus Compared with Continuous

Epidural Infusions for Labor Analgesia: A Systematic

Review and Meta-Analysis
Ronald B. George, MD, FRCPC,* Terrence K. Allen, MBBS, FRCA,† and
Ashraf S. Habib, MB, ChB, MSc, MHS, FRCA‡

BACKGROUND: The current standard labor epidural analgesic regimens consist of a local anes-
thetic in combination with an opioid delivered via continuous epidural infusion (CEI). With CEI
local anesthetic, doses may be large with resulting profound motor blockade potentially affect-
ing the incidence of instrumental deliveries. In this systematic review of randomized controlled
trials (RCTs), we compared the effect of intermittent epidural bolus (IEB) to standard CEI dosing
with or without patient-controlled epidural analgesia on patient satisfaction, the need for manual
anesthesia interventions, labor progression, and mode of delivery in healthy women receiving
labor epidural analgesia.
METHODS: A systematic review of RCTs that compared CEI with IEB for labor analgesia was
performed. The articles were evaluated for validity, and data were extracted by the authors and
summarized using odds ratios (ORs), mean differences (MDs), and 95% confidence intervals (CIs).
RESULTS: Nine RCTs were included in this systematic review. Three hundred forty-four subjects
received CEI, whereas 350 subjects received IEB labor analgesia. All 9 studies were deemed to
be low risk of bias. There was no statistical difference detected between IEB and CEI in the rate
of cesarean delivery (OR, 0.87; 95% CI, 0.56–1.35), duration of labor (MD, −17 minutes; 95%
CI, −42 to 7), or the need for anesthetic intervention (OR, 0.56; 95% CI, 0.29–1.06). IEB did
result in a small but statistically significant reduction in local anesthetic usage (MD, −1.2 mg
bupivacaine equivalent per hour; 95% CI, −2.2 to −0.3). Maternal satisfaction score (100-mm
visual analog scale) was higher with IEB (MD, 7.0 mm; 95% CI, 6.2–7.8).
CONCLUSIONS: IEB is an appealing concept; current evidence suggests IEB slightly reduces
local anesthetic usage and improves maternal satisfaction. Given the wide CIs of the pooled
results for many outcomes, definite conclusions cannot be drawn for those outcomes, but there
is also a potential that IEB improves instrumental delivery rate and need of anesthesia interven-
tions. More study is required to conceptualize the ideal IEB regimen and investigate its effect on
labor analgesia and obstetric outcomes.  (Anesth Analg 2013;116:133–44)

C
hildbirth is arguably one of the most painful expe-
riences a woman can undergo.1 The degree of pain
experienced and the quality of pain relief affect
patients’ satisfaction with the birthing process and may have
long-term emotional and psychological effects.2 The quality
of labor neuraxial analgesia has surpassed parenteral opi-
oids, nitrous oxide, and nonpharmacologic measures, with
limited effect on the mode of delivery and maternal and
neonatal outcomes.3
From the *IWK Health Centre, Dalhousie University, Halifax, Nova Scotia,
Canada; †Division of Women’s Anesthesia, Duke University Medical Cen-
ter, Durham; and ‡Department of Anesthesiology, Duke University Medical
Center, Durham, North Carolina.
Accepted for publication August 14, 2012.
Reprints will not be available from the authors.
Dr. George acknowledges the Canadian Anesthesiologists Research Founda-
tion for the 2011 CAS Career Scientist Award in Anesthesia.
The authors declare no conflicts of interest.
This report was previously presented, in part, at the Society of Obstetric
Anesthesia and Perinatology Annual Meeting 2011, Canadian Anesthesiolo-
gists’ Society Annual Meeting 2011.
Address correspondence to Ronald B. George, MD, FRCPC, Department of
Women and Obstetric Anesthesia, IWK Health Centre, Dalhousie University,
5850/5980 University Avenue, PO Box 9700, Halifax, NS, Canada B3K 6R8.
Address e-mail to rbgeorge@dal.ca.
Copyright © 2012 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e3182713b26
The current standard labor epidural analgesic regimens
in many institutions in North America and Europe consist
of a local anesthetic in combination with an opioid deliv-
ered via continuous epidural infusion (CEI) with or with-
out patient-controlled epidural analgesia (PCEA) boluses.
Despite improved analgesia with CEI with or without
PCEA compared with nonneuraxial analgesia, local anes-
thetic doses may be large with resulting profound motor
blockade.4 This reduces mobility, pelvic muscle tone, and
may impair the ability to “bear down” during the second
stage of labor, potentially resulting in increased rates of dys-
tocia and instrumental deliveries.5
In the continuing evolution of labor analgesia, rather
than delivering the local anesthetic continuously, small
regularly spaced intermittent boluses may lead to a more
extensive spread of local anesthetic in the epidural space.6
Therefore, the same dose of local anesthetic given via inter-
mittent epidural bolus (IEB) may provide improved analge-
sia. Research into IEB is growing, and medical devices are in
development. A shift in current practice from CEI (with or
without PCEA) to IEB (with or without PCEA) will require
enhanced pump technology and acceptance by obstetric
anesthesiologists to justify the cost of pump replacement to
hospital administration. Previous systematic reviews have
addressed labor epidural analgesia versus no analgesia
and alternate forms of neuraxial analgesia.7–9 van der Vyver

January 2013 • Volume 116 • Number 1 www.anesthesia-analgesia.org 133

Intermittent Epidural Bolus: A Systematic Review
et al.10 systematically reviewed traditional PCEA versus
CEI; however, their study was published in 2002, before the
use of IEB dosing. We, therefore, performed this systematic
review of randomized controlled trials (RCTs) to compare
the effects of IEB to standard CEI dosing with or without
PCEA in healthy women receiving labor epidural analge-
sia. Specifically, we investigated whether IEB compared
with CEI affects patient satisfaction, the need for manual
anesthesia interventions, labor progression, and mode of
delivery.
METHODS
The current meta-analysis adhered to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines for reporting meta-analyses.11 The
Cochrane Central Register of Controlled Trials (CENTRAL),
MEDLINE (PubMed), Excerpta Medica Database (EMBASE),
Cumulative Index to Nursing and Allied Health Literature
(CINAHL), and the Web of Science (Science Citation Index/
Social Science Citation Index [SCI/SSCI]) were searched.
CENTRAL, EMBASE, CINAHL, and SCI/SSCI were last
searched in July 2011. The PubMed search was last updated
on July 4, 2012. MeSH terms relating to labor analgesia and
neuraxial anesthetic techniques (analgesia, epidural; anes-
thesia, obstetrical; pregnancy; analgesia, patient-controlled)
were combined with text searches for “intermittent” and
“automated” and relevant synonyms. The results of these
searches were combined with a sensitive methodologic filter
for RCTs found in Section 6.4.11.1 of the Cochrane Handbook
for Systematic Reviews of Interventions.12 No restrictions, other
than those intrinsic to the database being searched, were
placed on the dates of publication. The reference lists from
retrieved RCTs were screened to identify additional trials,
as were recent tables of contents for the leading anesthe-
sia journals.a A search by author for any individual who
appears as an author on 2 or more relevant articles was com-
pleted. Using PubMed’s “See related articles” function with
relevant trials, additional references were sought. In addi-
tion, citation records for all relevant RCTs were searched
and reviewed with SCI/SSCI. No restrictions with respect
to language were included. Unpublished meeting abstracts
were not searched, only published RCTs were sought. An
attempt was made to contact authors regarding any clari-
fication of primary outcome measures; unpublished data
were not requested.
Study Identification
The types of studies considered for this review included
all published RCTs involving a comparison of IEB dosing
for maintenance of labor epidural analgesia compared with
traditional CEI dosing with or without PCEA. Specifically,
participants were healthy laboring women (nulliparous and
parous) with lumbar epidural catheters placed for labor
analgesia (induced or spontaneous). Primary outcomes
analyzed included patient satisfaction, anesthesia interven-
tions, labor progression, and mode of delivery (vaginal,
January 1, 2012, to July 4, 2012—International Journal of Obstetric Anesthesia,
a
Anesthesia & Analgesia, Anesthesiology, Canadian Journal of Anesthesia,
Anaesthesia, and British Journal of Anaesthesia.
134   
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instrumental vaginal, or cesarean delivery [CD]). Secondary
outcomes included degree of motor blockade, degree of
sensory blockade, time to first anesthetic intervention, local
anesthetic dose delivered per hour, presence of pruritus,
shivering, maternal fever, nausea and vomiting, neona-
tal Apgar scores at 1 minute and 5 minutes, and umbilical
artery and vein pH. Studies were included if they reported
any of the primary outcomes. Disagreements regarding
inclusion of potentially eligible trials were resolved by dis-
cussion and, if necessary, arbitration by a third reviewer.
Data Extraction and Assessment
Data were extracted independently by 2 authors (RG and
AH). No predesigned data sheet was used. When data were
presented as medians, ranges, and confidence intervals
(CIs), the mean and standard deviations were calculated as
per Hozo et al.13 Two reviewers (RG and TA) independently
assessed the quality (i.e., risk of bias) of all included stud-
ies using criteria adapted from Furlan et al.14 Each of the
12 criteria were scored as yes, no, or unclear. Studies that
met ≥6 of the criteria were rated as having a “low risk of
bias.” In the event that discussion was unable to solve a dis-
agreement between the 2 reviewers, the opinion of the third
reviewer (AH) was sought. An a priori sensitivity analysis
was planned excluding studies with high risk of bias.
Epidural dose calculations were calculated from sum-
marized data by dividing total dose delivered by the mean
duration of labor or duration of analgesia delivery reported
in each study. Local anesthetic doses were converted to mil-
ligram equivalents of bupivacaine per hour of anesthesia
delivery. Ropivacaine and levobupivacaine were assumed
to be approximately 60% as potent as bupivacaine.15–17
All data pertaining to the predetermined outcome mea-
sures were transcribed to RevMan 5 for meta-analysis
(Version 5.1. Copenhagen: The Nordic Cochrane Centre, The
Cochrane Collaboration, 2011). If meta-analytic methods
were not possible, the data were simply presented qualita-
tively. All data were analyzed using a random-effects model
due to clinical or methodologic heterogeneity. Continuous
variables were reported as mean difference (MD) with 95%
CI, while dichotomous data were reported as odds ratios
(OR) with 95% CI. Heterogeneity was assessed with the I2
statistic that describes the percentage of variation across
studies that is due to heterogeneity rather than chance.18
A P < 0.1 was considered statistically significant heteroge-
neity, and I2 > 50% was considered to indicate significant
heterogeneity. Heterogeneity was explored by performing
a sensitivity analysis excluding outlier studies if they were
methodologically different from other studies. Publication
bias was formally assessed with the Egger test.19
RESULTS
The results of the literature search are outlined in Figure 1.
After screening, 21 articles were selected for in-depth full-
text review, from which 9 articles were deemed eligible for
inclusion in this systematic review.20–28 The 12 excluded
citations clearly did not include a randomized compari-
son of IEB dosing of a labor epidural compared with stan-
dard CEI.29–40 Three hundred forty-four subjects received
CEI, while 350 subjects received IEB labor analgesia. Study
characteristics and risk of bias assessment are included in
ANESTHESIA & ANALGESIA
Figure 1. 
Manuscript selection flow
diagram.
Tables 1 and 2. All 9 studies were deemed low risk of bias.
Spontaneous onset of labor was an inclusion criteria in 4
studies.20,21,24,27 However, 3 of the 4 studies reported a per-
centage of women who received preanalgesia oxytocin.21,24,27
Two studies reported the portion of women whose labor
was induced.22,26 Wong et al.28 only recruited parous women
for induction of labor. Two studies reported the preanalge-
sia use of oxytocin.23,25
Mode of Delivery
Of the 9 included trials, 8 reported data on the mode of
delivery. These 8 studies included 652 subjects.20,22–28 None
of the studies reported a significant difference in the CD
rate. Pooled results also did not show a difference in the rate
of CD (OR, 0.87; 95% CI, 0.56–1.35; Fig. 2). Similarly, none
of the studies reported a reduction in instrumental delivery
rate except the study by Capogna et al.20 This was the only
study designed and powered to detect a difference in instru-
mental delivery rates and reported a significant reduction
with IEB compared with CEI (7% vs 20%; P = 0.03).20 The
pooled results for these 8 studies approached but did not
achieve statistical significance with reduction of instru-
mental delivery rate with IEB (OR, 0.59; 95% CI, 0.35–1.00;
Fig. 3). Wong et al.28 recruited only parous women, while the
other studies contained only nulliparous women. Excluding
the study by Wong et al.28 had no effect on pooled results
January 2013 • Volume 116 • Number 1 www.anesthesia-analgesia.org   135
(cesarean delivery OR, 0.85; 95% CI, 0.55–1.33; instrumental
delivery OR, 0.57; 95% CI, 0.32–1.00). There was no publi-
cation bias for CD (P = 0.27) or instrumental delivery (P =
0.48).
Duration of Labor
Of the 9 included studies, 8 reported the total duration of
labor or duration of labor analgesia (n = 652),20,22–28 while
only 5 reported the duration of the second stage of labor
(n = 321).22–24,26,27 There was no statistically significant dif-
ference in total duration of labor between IEB and CEI
(Fig. 4A). The duration of second stage of labor was statis-
tically significantly shortened in the IEB group (MD, −12
minutes; 95% CI, −23 to 0; Fig. 4B). There was no publica-
tion bias for duration of labor (P = 0.06) or second stage of
labor (P = 0.82).
Anesthesia Interventions
Of the 9 included trials, 8 reported data on the need for
manual boluses of local anesthetic by the anesthesia care-
giver.20–25,27,28 These 8 studies included 567 subjects (Fig. 5).
Capogna et al.20 reported that no subjects in either group
required an anesthetic intervention. There was no statisti-
cally significant reduction in the need for additional anes-
thetic intervention (OR, 0.56; 95% CI, 0.29–1.06). The time to
a subject’s first anesthetic intervention was not significantly
136   
Table 1.  Study Characteristics and Risk of Bias Assessment of Included Studies
Combined spinal
epidural–subarachnoid Spontaneous/induced Risk of bias
Study n Parity medications Epidural solution CEI regimen IEB regimen labor, n (%) assessment14
Capogna et al.20 145 Nulliparous N/A Levobupivacaine, 0.0625%– 10 mL/h (0.0625%) + 10 mL (0.0625%) bolus every hour Spontaneous labora; Low risk
0.125%; sufentanil, 0.5 PCEA (5 mL bolus, + PCEA (5 mL bolus, 10 minute oxytocin use not
µg/mL 10 minute lockout, lockout, 0.125%) (n = 75) reported

www.anesthesia-analgesia.org
0.125%) (n = 70)
Chua and Sia21 42 Nulliparous Fentanyl, 25 µg Ropivacaine, 0.1%; fentanyl, 5 mL/h (n = 21) 5 mL bolus every hour (n = 21) Spontaneous labora; Low risk
Intermittent Epidural Bolus: A Systematic Review

2 µg/mL preanalgesia oxytocin;

CEI, 8 (38); IEB, 9 (43)
Fettes et al.22 40 Nulliparous N/A Ropivacaine, 0.2%; fentanyl, 10 mL/h (n = 20) 10 mL bolus every hour (n = 20) Induction of labor; CEI, 12 Low risk
2 µg/mL (60); IEB, 14 (70)
Leo et al.23 62 Nulliparous Ropivacaine, 2 mg; Ropivacaine 0.1%; fentanyl 5 mL/h + PCEA (5 mL 5 mL bolus every hour (or 30 Preanalgesia oxytocin; CEI, Low risk
fentanyl, 15 µg 2 µcg/mL bolus, 10 minute minutes after successful PCEA 10 (32); IEB, 15 (48)
lockout) (n = 31) dose) + PCEA (5 mL bolus, 10
minute lockout) (n = 31)
Lim et al.25 60 Nulliparous Fentanyl, 25 µg Levobupivacaine, 0.1%; 10 mL/h (n = 30) 5 mL bolus every 30 minutes Preanalgesia oxytocin; CEI, Low risk
fentanyl, 2 µg/mL (n = 30) 4 (13); IEB, 9 (30)
Lim et al.24 50 Nulliparous Ropivacaine, 2 mg; Ropivacaine, 0.1%; fentanyl, 10 mL/h (n = 25) 2.5 mL bolus every 15 minutes Spontaneous labora; Low risk
fentanyl, 15 µg 2 µg/mL (initiated 7.5 minutes after SA preanalgesia oxytocin;
dose) (n = 25) CEI, 10 (40); IEB, 5 (20)
Salim et al.26 127 Nulliparous N/A Bupivacaine, 0.125%– 8 mL/h (0.125%) + 10 mL bolus every hour (0.25%) Induction of labor; CEI, 17 Low risk
0.25%; fentanyl, 2 µg/mL PCEA (3 mL bolus, (n = 64) (27); IEB, 14 (22)
20 minute lockout)
(n = 63)
Sia et al.27 42 Nulliparous Ropivacaine, 2 mg; Ropivacaine, 0.1%; fentanyl, 5 mL/h + PCEA (5 mL 5 mL bolus every hour (or 1 hour Spontaneous labora; Low risk
fentanyl, 15 µg 2 µg/mL bolus, 10 minute after successful PCEA dose) preanalgesia oxytocin;
lockout) (n = 21) (n = 21) CEI, 5 (24); IEB, 7 (33)
Wong et al.28 126 Parous Bupivacaine, 1.25 mg; Bupivacaine, 0.625%; 12 mL/h + PCEA (5 mL 6 mL bolus every 30 minutes + Induction of labora; CEI, 63 Low risk
fentanyl, 15 µg fentanyl 2, µg/mL bolus, 10 minute PCEA (5 mL bolus, 10 minute (100); IEB; 63 (100)
lockout) (n = 63) lockout) (n = 63)
CEI = continuous epidural infusion; IEB = intermittent epidural bolus; PCEA = patient-controlled epidural analgesia; SA = subarachnoid.
a
Reported as an inclusion criteria.

ANESTHESIA & ANALGESIA

 different between groups (MD, 17 minutes; 95% CI, −28 to

Wong et al.28
62; Fig. 6). Significant heterogeneity was observed for the

Yes
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes

Yes
No
time to first interventions outcome (I2 = 74%). Chua et al.21
appear to add significant heterogeneity to this analysis.
Removing this study abolishes this heterogeneity (I2 = 0%)
with no effect on pooled results (MD, −7 minutes; 95% CI,
Sia et al.27

−37 to 24). Wong et al.28 and Sia et al.27 did not report time
Yes
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes
to first anesthesia intervention. Sia et al.,27 reported no sig-
nificant difference in the pain-free interval between CEI and
IEB. Wong et al.28 did report the time to first PCEA usage,
Salim et al.26

and this was not significantly different between the IEB and
Unsure
Unsure
Unsure
Yes
Yes

Yes
Yes

Yes
Yes
Yes
Yes
CEI groups. There was no publication bias for manual inter-
No
ventions (P = 0.57) or time to intervention (P = 0.15).

Dose of Local Anesthetic

Lim et al.24

The specific regimens and local anesthetic concentrations are

Yes
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes
listed in Table 1. Of the 9 included studies, 3 published data
regarding the total dose of local anesthetic per hour during
the study period.23,24,28 Five other studies20,22,25–27 reported the
Lim et al.25

total dose given. The study of Chua et al.21 was not included
Unsure
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes

in this analysis because the study concluded with the first

No
No
No

need for anesthetic intervention. With these 8 studies (n =

652) there was a statistically significant reduction in total
local anesthetic delivered with IEB (MD, −1.2 mg bupiva-
Leo et al.23

caine equivalents per hour; 95% CI, −2.2 and −0.3; I2 = 83%;
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes
No

Fig. 7A). Salim et al.26 used a concentrated local anesthetic

mixture for their IEB group, different from their CEI group;
therefore, we performed a sensitivity analysis excluding this
Fettes et al.22

study. The effect was smaller but still statistically significant

in favor of IEB with less heterogeneity (MD, −0.7 mg/h; 95%
Yes
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes

Yes
No

CI, −1.2 to −0.2; I2 = 40%; Fig. 7B). There was no publication

bias for local anesthetic consumption (P = 0.26).
Chua and Sia21

Maternal Satisfaction
Overall maternal satisfaction with labor analgesia was
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes
No

reported in 5 of the included studies.23–25,27,28 Four studies

reported maternal satisfaction with a verbal rating scale
(VRS) where 0 is very dissatisfied and 100 is extremely sat-
isfied.23–25,27 Wong et al.28 reported maternal satisfaction with
Capogna et al.20

a 100-mm visual analog scale (VAS) score. Pooled data from

the 5 studies showed greater maternal satisfaction in the IEB
Yes
Yes
Yes
Yes
Yes

Yes
Yes

Yes

Yes
Yes
Yes
Yes
Table 2.  The Risk of Bias of Included Studies14

groups (MD, 7.0 mm; 95% CI, 6.2–7.8; Fig. 8). Exclusion of
the study by Wong et al.28 did not have a significant effect
on the pooled results (MD, 7.1 mm; 95% CI, 5.0–9.2). There
was no publication bias for maternal satisfaction (P = 0.84).
Was the timing of the outcome assessment similar?
Was the care provider blinded to the intervention?

Were all randomized participants analyzed in their

Was the dropout rate described and acceptable?

Was the compliance acceptable in all groups?

Subgroup Analysis of Primary Outcomes

Are reports of the study free of suggestion of
Was the method of randomization adequate?

Was the patient blinded to the intervention?

Each of the primary outcomes had a subgroup analysis

Was the outcome assessor blinded to the
Was the treatment allocation concealed?

Were cointerventions avoided or similar?

completed based on: (1) the use of a combined spinal–epi-

Were the groups similar at baseline?

dural (CSE) technique to initiate labor analgesia and (2) the

use of PCEA during maintenance of labor analgesia. Five
selective outcome reporting?

studies initiated analgesia with a CSE.21,23–25,27 The initia-

tion of labor analgesia with a CSE did not have a significant
effect on any of the primary outcomes. The use of PCEA for
allocated group?

maintenance of labor analgesia made a noteworthy effect on

intervention?

the duration of the first stage of labor and the total duration
of labor. When PCEA was used for maintenance of labor,
the duration of first stage was longer with IEB23,26,27 (MD,
20 minutes; 95% CI, −22 to 61). However, when PCEA was
not used for maintenance of labor, the duration of first stage

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Intermittent Epidural Bolus: A Systematic Review
Figure 2.  Forest plot for mode of delivery (cesarean). CEI = continuous epidural infusion; IEB = intermittent epidural bolus.
Figure 3.  Forest plot for mode of delivery (instrumental). CEI = continuous epidural infusion; IEB = intermittent epidural bolus.
was shorter with IEB22,24 (MD, −61 minutes; 95% CI, −129
to 6; Fig. 9). The total duration of labor was reduced with
IEB when PCEA was not used22,24,25 (MD, −86 minutes; 95%
CI, −146 to −27), but not when it was used20,23,26–28 (MD, −4
minutes; 95% CI, −26 to 17; Fig. 4A).
Additional Outcomes
Other than dose of local anesthetic, most of the secondary
outcomes were infrequently reported. A meta-analysis was
completed on specific outcomes that contained data from
more than 1 study. There were no significant differences
between the groups with respect to these outcomes. The
results are summarized in Table 3.
Umbilical pH values and 1-minute Apgar scores were
only reported in 1 study (no significant difference).22 The
5-minute Apgar was reported in 4 studies,22–25 in which the
MD was −0.04 with a 95% CI of −0.2 to 0.1. The degree of
sensory block was quantified in 4 studies. Leo et al.23 and
Lim et al.24 reported the sensory block level at the first
request for additional analgesia. Chua et al.21 reported the
maximal sensory block level within the first 3 hours of
analgesia, while Sia et al.27 reported the maximal sensory
block during the entire study period. Within these studies,
there was no significant difference between CEI and IEB
with respect to sensory blockade. Capogna et al.20 designed
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their study to detect a clinically significant degree of motor
blockade measured with the Bromage score modified by
Breen et al.41 In their study, the incidence of motor block
(defined as modified Bromage score 41 <6, i.e., the inability
to stand and complete a partial knee bend) at least once
during labor was significantly increased in the CEI group
compared with the IEB group (26/70 vs 2/75, P < 0.001).
Assuming the modified Bromage score <620 is equivalent to
a traditional Bromage score >1,21,27,28 then the pooled results
are not statistically significant (Table 3).
DISCUSSION
Nine high-quality low risk of bias RCTs have evaluated IEB
versus CEI in laboring women. In healthy women requesting
labor epidural analgesia, the mode of maintenance of
epidural analgesia may not affect the mode of delivery.
However, intermittent bolus dosing of local anesthetic may
be associated with reduced local anesthetic consumption,
decreased anesthetic interventions, and an improvement
in maternal satisfaction when compared with those women
receiving CEI. The 2 techniques of local anesthesia delivery
appear to be comparable in terms of total duration of labor,
but there was a statistically significant reduction in the
length of the second stage of labor with IEB. The duration of
the second stage was a much as 22 minutes shorter with IEB.
Arguably, this may enter the realm of clinically significant,
ANESTHESIA & ANALGESIA
Figure 4.  A, Forest plot for the total duration (minutes) of labor and the subgroup analysis for patient-controlled epidural analgesia (PCEA)
maintenance of labor analgesia. B, Forest plot for the duration (minutes) of second stage of labor. CEI = continuous epidural infusion; IEB =
intermittent epidural bolus.

Figure 5.  Forest plot for required anesthetic interventions. CEI = continuous epidural infusion; IEB = intermittent epidural bolus.

and IEB may positively affect labor progression. Although
there was no statistically significant difference between the
2 groups with regard to the incidence of adverse events
(Table 3), the wide CIs of the pooled results preclude us
from making any conclusions.
Despite not reaching statistical significance, several
outcomes should be considered potentially clinically
significant. The pooled results for instrumental delivery
rate, rate of anesthetic interventions, and duration of labor
each have wide CIs that contain clinically significant end
points, therefore precluding us from drawing conclusions
from the pooled data for those outcomes. For instance
the lower end CI for the OR for instrumental delivery is
0.35, a clinically significant possibility with IEB. With a

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Intermittent Epidural Bolus: A Systematic Review

Figure 6.  Forest plot for time (minutes) to first required anesthetic intervention. CEI = continuous epidural infusion; IEB = intermittent epidural
bolus.

Figure 7. A and B, Forest plot for milligrams per hour of local anesthetic (bupivacaine equivalents) delivered. CEI = continuous epidural
infusion; IEB = intermittent epidural bolus.

Figure 8.  Forest plot for maternal satisfaction (visual analog scale [VAS]28 0–100 mm; verbal rating scale [VRS]23–25,27 0–100; 0 = very dissatisfied,
100 = extremely satisfied). CEI = continuous epidural infusion; IEB = intermittent epidural bolus.

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Figure 9.  Forest plot for the duration (minutes) of first stage of labor and the subgroup analysis for patient-controlled epidural analgesia
(PCEA) maintenance of labor analgesia. CEI = continuous epidural infusion; IEB = intermittent epidural bolus.

Table 3.  Secondary Outcomes

Number of events/total in Number of events/total in continuous Odds ratio (95%
Outcome Studies intermittent epidural bolus group epidural infusion group confidence interval)
Nausea Lim et al.24,25 10/107 (9.3%) 3/107 (2.8%) 2.83 (0.85–9.46)
Sia et al.27
Leo et al.23
Vomiting Lim et al.24,25 9/107 (8.4%) 3/107 (2.8%) 3.21 (0.83–12.47)
Sia et al.27
Leo et al.23
Pruritus Lim et al.24,25 62/107 (57.9%) 62/107 (57.9%) 1.00 (0.57–1.75)
Sia et al.27
Leo et al.23
Hypotension Lim et al.24,25 7/148 (4.7%) 3/148 (2.0%) 1.70 (0.45–6.34)
Sia et al.27
Fettes et al.22
Chua et al.21
Leo et al.23
Motor blockade Chua et al.21 5/180 (2.8%) 28/175 (16.0%) 0.47 (0.05–4.14)
Sia et al.27
Wong et al.28
Capogna et al.20

heterogeneity measure of zero, 8 studies contributing to a
very close statistical significance (P = 0.05) and an absolute
risk difference of 5.2% suggest a number-needed-to-treat of
20 to prevent 1 instrumental delivery. The effect size of 0.59
suggests that future trials of IEB should include approxi-
mately 486 participants (G-Power v 3.0 2006, Mannheim,
Germany) to show a statistically significant reduction in
the instrumental delivery rate compared with standard
CEI.42 Induced versus spontaneous labor is a potential fac-
tor in these important outcomes; however, not all studies
restricted the inclusion criteria nor specifically reported this
event; therefore, a subgroup analysis was not possible.
Interference with normal labor progression leading to
instrumental deliveries is a potentially unfavorable out-
come of labor analgesia. However, modern labor analgesia
with low concentrations of local anesthetics can be admin-
istered without adversely affecting labor outcomes.42 In the
Comparative Obstetric Mobile Epidural Trial (COMET) con-
ducted in the United Kingdom, Wilson et al.43 demonstrated
that despite improved analgesia and lower doses of local
anesthetic in the CSE analgesia arm of the study, this tech-
nique did not alter delivery modality or duration of labor.
Despite the lack of statistical significance to alter labor out-
comes with IEB delivery of epidural analgesia, the improve-
ment in maternal satisfaction, which may loosely reflect
improved analgesia, is still an important goal for labor anal-
gesia research.
Satisfaction with labor analgesia is an important outcome
of the quality of care given to women. It is a complex measure
commonly used to describe overall adequacy of pain relief.
However, maternal satisfaction involves many factors—
maternal involvement in decision making, perception of
emotional control, maternal expectations, and labor pain.44–46
Furthermore, labor pain is more than a simple physiological
process; it is a complex reaction for which inadequately
validated measures of maternal satisfaction, such as VAS
and VRS measures, may or may not necessarily correlate
to the effectiveness of pain relief.47,48 Given the complexity

January 2013 • Volume 116 • Number 1 www.anesthesia-analgesia.org   141

Intermittent Epidural Bolus: A Systematic Review
of measuring satisfaction, the different scales used, and the
timing of such a measure, the lack of heterogeneity (I2 = 0%)
should be interpreted with caution.
All of the studies had small sample sizes reflecting the
difference in the outcomes they were powered to detect.
Two trials were powered to detect a difference in the dose of
local anesthetic delivered.27,28 A single study was powered
to detect a difference in the duration of labor.26 Fettes et al.22
powered their study to detect a difference in VAS score at an
arbitrary time, 4 hours after the intervention. Four studies
were powered to detect a difference in need for anesthesia
interventions.21,23–25 Other than Capogna et al.,20 none of the
included trials was powered to detect a difference in the
side effects of labor analgesia. No studies were powered to
detect a difference in maternal satisfaction.
Capogna et al.20 published the largest and most recent
trial, which was powered to detect a difference in the inci-
dence of motor blockade (primary outcome) and instru-
mental deliveries (secondary outcome). They reported a
greater incidence of motor blockade with CEI using the
modified Bromage score, which may be more sensitive than
the traditional Bromage score.41 The authors suggested
that the greater incidence of motor blockade and subse-
quent higher instrumental delivery rate in the CEI group
compared with other similar trials was due to the longer
duration of observation in their study. However, the dura-
tion of labor was not significantly longer in this trial and
was likely shorter than average. The dramatic decrease in
instrumental delivery rate is likely related to the reduced
motor blockade. Perhaps the CEI infusion that was started
immediately after induction of analgesia or the increased
number of patients who used the higher concentration
0.125% levobupivacaine PCEA option in the CEI group
added significantly to the cumulative dose of levobupi-
vacaine and subsequent increased motor blockade. The
ultralow dose regimen for epidural analgesia based on the
study by Capogna et al.20 and the reduced PCEA use in the
IEB group and subsequent reduced motor blockade appear
to eloquently display a potential benefit of IEB. Whether it
was the higher PCEA use in the CEI group or the character-
istics of IEB with 0.0625% levobupivacaine, they both seem
to deliver appropriate analgesia, as neither group required
a manual anesthetic intervention. This came at the cost of
increased motor blockade and instrumental delivery in the
CEI group.
This review has several limitations. There was significant
inconsistency with regard to reporting of outcomes. Each
of the included studies reported at least 1 primary out-
come, but none of the included studies included all primary
outcomes reported in this systematic review. Each study,
except Sia et al.,27 found at least 1 significant difference in
a primary outcome measure. Measures of analgesia such
as pain scores reported using VAS, VRS, or numeric rating
scales were not measured at standard intervals. In contrast,
maternal satisfaction was nearly consistently reported and
may represent a surrogate measure of analgesia. The study
by Wong et al.28 was the only study to recruit parous sub-
jects; in fact, they only included parturients with at least
1 previous vaginal delivery (126 subjects). The remaining
studies only included uncomplicated nulliparous women.
142   
www.anesthesia-analgesia.org
This likely limits our ability to extrapolate our conclusions
to women presenting with multiple gestations and parous
women. Because of the small number of studies, a meta-
regression was not conducted to control for factors known
to affect the outcomes of interest.
There was significant clinical heterogeneity among stud-
ies with regard to labor analgesia initiation, specific local
anesthetic and concentration, and drug delivery regimens.
A subgroup analysis of the effect of PCEA maintenance and
CSE analgesia initiation yielded only a potential interaction
between PCEA, IEB, and the duration of labor. Because of
the small number of studies, the relatively youthful field of
IEB, and the variety of analgesia regimens, sensitivity anal-
ysis of these dosing variables was not part of this analysis.
Currently, because of IEB with PCEA equipment not being
readily available, standardization of equipment among
institutions is nearly impossible. Specifically, the dosing
volumes and intervals varied among the studies, and it is
unknown whether this influenced the reported outcomes.
Much like the debates regarding the ideal regimen of CEI
combined with PCEA, the search for the ideal IEB regimen
is sure to inspire future studies. Wong et al.49 have initiated
this avenue of research. They recently compared 3 regimens
of IEB and PCEA: 2.5 mL every 15 minutes, 5 mL every 30
minutes, and 10 mL every 60 minutes of 0.625 mg/mL bupi-
vacaine with 1.95 µg/mL of fentanyl. The 10/60 group did
consume less bupivacaine, and the 2.5/15 group appeared
to require more interventions for poor analgesia, but oth-
erwise all 3 groups were very similar with respect to mode
of delivery, PCEA usage, manual anesthesia interventions,
pain scores, and motor blockade. Future studies will need
to be powered to detect the small differences that may exist
between the extremes of bolus size. Accepting that the low-
dose epidural regimens of Wong et al.49 and Capogna et al.20
are likely near the ideal concentration, the trends suggest
that larger volume boluses may be required.
In summary, IEB may be associated with reduced local
anesthetic consumption, shorter second stage of labor, and
higher maternal satisfaction but possibly no difference
in mode of delivery or required anesthetic interventions
compared with CEI. As previously noted, the wide CIs
for the pooled results of some of the reported outcomes
do contain clinically significant differences, such as the
potential for a clinically significant reduction in the
instrumental delivery rate with IEB. Further research of IEB
for labor analgesia is necessary before definite conclusions
can be made. Current epidural pump technology does not
allow using IEB with PCEA, and changing current practice
would require a significant financial influx to labor wards
for the required pump technology and education. On the
basis of the findings of this systematic review and meta-
analysis, current evidence suggests that there may be
potential improvements in instrumental delivery rates
and rates of anesthesia interventions, so more studies are
required to conceptualize the ideal IEB/PCEA regimen
and then consistently show an improvement in labor
analgesia and a greater effect on obstetric outcomes. The
new pump technology required for this new technique
and the cost that this entails could easily be justified by
improved outcomes.  E
ANESTHESIA & ANALGESIA
DISCLOSURES
Name: Ronald B. George, MD, FRCPC.
Contribution: This author helped design and conduct the
study, analyze the data, and write the manuscript.
Attestation: Ronald B. George has seen the original study data,
reviewed the analysis of the data, approved the final manu-
script, and is the author responsible for archiving the study
files.
Name: Terrence K. Allen, MBBS, FRCA.
Contribution: This author helped conduct the study, analyze
the data, and write the manuscript.
Attestation: Terrence K. Allen has seen the original study
data, reviewed the analysis of the data, and approved the final
manuscript.
Name: Ashraf S. Habib, MB, ChB, MSc, MHS, FRCA.
Contribution: This author helped conduct the study, analyze
the data, and write the manuscript.
Attestation: Ashraf S. Habib has seen the original study data,
reviewed the analysis of the data, and approved the final
manuscript.
This manuscript was handled by: Cynthia A. Wong, MD.
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