Anaesthesia 2023, 78, 1129–1138 doi:10.1111/anae.

16060

Original Article

High-volume patient-controlled epidural vs. programmed

intermittent epidural bolus for labour analgesia: a
randomised controlled study
 ,1 S. Fieuws,4 S. Rex,5,6
E. Roofthooft,1,2 N. Filetici,3 M. Van Houwe,3 P. Van Houwe,1 A. Barbe
7 5,6
C. A. Wong and M. Van de Velde

1 Consultant, Department of Anaesthesiology, GZA Sint Augustinus Hospital, Antwerp, Belgium

2 PhD Student, 6 Professor, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
3 Resident, 5 Consultant, Department of Anaesthesiology, University Hospitals Leuven, Leuven, Belgium
4 Professor, Department of Public Health and Primary Care, KU Leuven – University of Leuven, Leuven, Belgium
7 Professor, Department of Anesthesia, University of Iowa, Iowa City, IA, USA

Summary
The aim of neuraxial analgesia is to achieve excellent pain relief with the fewest adverse effects. The most
recently introduced technique for epidural analgesia maintenance is the programmed intermittent epidural
bolus. In a recent study, we compared this with patient-controlled epidural analgesia without a background
infusion and found that a programmed intermittent epidural bolus was associated with less breakthrough pain,
lower pain scores, higher local anaesthetic consumption and comparable motor block. However, we had
compared 10 ml programmed intermittent epidural boluses with 5 ml patient-controlled epidural analgesia
boluses. To overcome this potential limitation, we designed a randomised, multicentre non-inferiority trial using
10 ml boluses in each group. The primary outcome was the incidence of breakthrough pain and total analgesic
intake. Secondary outcomes included motor block; pain scores; patient satisfaction; and obstetric and neonatal
outcomes. The trial was considered positive if two endpoints were met: non-inferiority of patient-controlled
epidural analgesia with respect to breakthrough pain; and superiority of patient-controlled epidural analgesia
with respect to local anaesthetic consumption. A total of 360 nulliparous women were allocated randomly to
patient-controlled epidural analgesia-only or programmed intermittent epidural bolus groups. The patient-
controlled group received 10 ml boluses of ropivacaine 0.12% with sufentanil 0.75 lg.ml-1; the programmed
intermittent group received 10 ml boluses supplemented by 5 ml patient-controlled boluses. The lockout
period was 30 min in each group and the maximum allowed hourly local anaesthetic/opioid consumption was
identical between the groups. Breakthrough pain was similar between groups (11.2% patient controlled vs.
10.8% programmed intermittent, p = 0.003 for non-inferiority). Total ropivacaine consumption was lower in the
PCEA–group (mean difference 15.3 mg, p < 0.001). Motor block, patient satisfaction scores and maternal and
neonatal outcomes were similar across both groups. In conclusion, patient-controlled epidural analgesia is non-
inferior to programmed intermittent epidural bolus if equal volumes of patient-controlled epidural analgesia
are used to maintain labour analgesia and superior with respect to local anaesthetic consumption.

.................................................................................................................................................................
Correspondence to: E. Roofthooft
Email: eva_roofthooft@hotmail.com
Accepted: 9 May 2023
Keywords: breakthrough pain; labour analgesia; motor block; PCEA; PIEB
Presented in part as an oral abstract at the 2022 annual OAA meeting in Newport, UK and the 2022 annual ESRA meeting in
Thessaloniki, Greece.
Twitter: @CynthiaAWongMD; @MarcVandeVelde6

© 2023 Association of Anaesthetists. 1129


Anaesthesia 2023, 78, 1129–1138 Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia
Introduction
Neuraxial labour analgesia is a safe and effective method
of pain relief. Following initiation of analgesia with epidural
or combined spinal-epidural, this can be maintained with
continuous epidural infusion, manual intermittent boluses,
patient-controlled epidural analgesia (PCEA), programmed
intermittent epidural bolus (PIEB) or a combination of
these. Since its introduction by Gambling in 1988 [1], PCEA
has been established as the preferred mode of epidural
drug delivery for analgesia maintenance [2]. In comparison
with continuous epidural infusion, studies have shown that
PCEA decreases the incidence of breakthrough pain
requiring rescue interventions, reduces local anaesthetic
consumption without compromising analgesic efficacy and
increases patient satisfaction [3–6].
Programmed intermittent epidural boluses are the
most recently introduced of these maintenance techniques
[7]. Compared with continuous epidural infusion (with or
without PCEA), PIEB demonstrates better local anaesthetic
spread in the epidural space and better sensory blockade
with less breakthrough pain [7–16]. Some studies have also
demonstrated a lower incidence of motor block [6, 10, 11,
13, 15–19], lower incidence of operative vaginal deliveries
[6, 10, 11, 13, 15–17, 20], lower local anaesthetic
consumption [8, 10, 11, 13–16, 21–25] and improved
maternal satisfaction using PIEB compared with continuous
epidural infusion [9–11, 13, 15, 16, 18, 21, 23, 25].
Both techniques use intermittent bolus delivery, which
has been proven to improve local anaesthetic spread
compared with continuous infusion [7–16]. Previous studies
documenting the superiority of PIEB have, almost
exclusively, compared PIEB (with or without PCEA) with
continuous epidural infusion (with or without PCEA).
Recently, we compared an hourly 10 ml PIEB bolus
technique to a 5 ml PCEA with a 12-min lockout and no
background infusion [26]. Programmed intermittent
epidural bolus was associated with less breakthrough pain
and motor block, but higher consumption of local
anaesthetic. However, a limitation to our study is that we did
not compare equal bolus volumes and therefore may not
have delivered equipotent drug doses. To our knowledge,
there have been no comparisons of PCEA (without a
background infusion) to PIEB when similar epidural bolus
volume and delivery rate are used. We hypothesised that
PCEA without a background infusion would be non-inferior
to PIEB-PCEA if the same bolus dose were used, with similar
incidence of breakthrough pain, analgesia, motor block and
patient satisfaction, as well as lower local anaesthetic
consumption. To test our hypothesis, we performed a
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randomised, double-blind study in which breakthrough
pain, local anaesthetic consumption, pain scores,
satisfaction and motor block were compared in women who
received PIEB or PCEA without background infusion for
maintenance of labour analgesia. The trial was considered
positive if two endpoints were met: non-inferiority of PCEA
with respect to incidence of breakthrough pain; and
superiority of PCEA with respect to local anaesthetic
consumption.
Methods
This study was approved by the ethics committees from
both participating institutions in September 2019 and an
amendment to the protocol was approved in June 2020.
The following inclusion criteria were used: patient
requests neuraxial analgesia; nulliparous with ASA physical
status 2; singleton, term pregnancy; active labour; cervical
dilatation < 7 cm at time of request for analgesia; and
baseline pain score > 30 (visual analogue scale (VAS);
0 mm = no pain, 100 mm = worst imaginable pain).
Exclusion criteria included: ASA physical status 3 or 4;
known allergies to study drugs; contraindication to
neuraxial anaesthesia; age < 18 y; and non-Dutch speaking.
Eligible patients were given verbal and written information
and written consent was gained. Before siting the epidural,
peripheral intravenous access was established and 500 ml
Ringer’s lactate solution administered. Baseline maternal
heart rate and non-invasive arterial blood pressure were
recorded. A needle-through-needle combined spinal-
epidural technique was used at the L3–4 or L4–5 lumbar
interspace, with 4.8 mg of ropivacaine and 3 lg of
sufentanil for the intrathecal component. A multi-orifice
epidural catheter was inserted 4–5 cm into the epidural
space and secured. Women with a VAS score ≤ 20 achieved
within 30 min of the intrathecal injection were allocated
randomly to the two study groups using a computer-
generated permuted block randomisation list controlled for
study site (variable block-size with 1:1 allocation). Allocation
concealment was achieved using opaque, sealed envelopes
containing group assignments. An anaesthetist not involved
in patient management or data collection opened the
envelope when adequate spinal anaesthesia was achieved,
then programmed the epidural maintenance pump to the
appropriate algorithm and initiated therapy. Woman were
excluded from further study and randomisation if a VAS
score ≤ 20 was not achieved within 30 min of the intrathecal
injection.
In both groups, epidural analgesia was maintained
using ropivacaine 0.12% and sufentanil 0.75 lg.ml-1;
© 2023 Association of Anaesthetists.

Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia
maintenance therapy (starting the pump) was initiated 15–
30 min after the spinal injection, when VAS ≤ 20. In the PIEB
group, maintenance analgesia was initiated with an
automated 10 ml bolus administered 45 min after spinal
injection and maintained using a programmed bolus of
10 ml each hour, with additional 5 ml PCEA boluses
available with a 30-min lockout interval. In the PCEA-group,
analgesia was maintained using 10 ml PCEA boluses with a
30-min lockout interval (PCEA-only). The first PCEA bolus
was allowed 45 min after spinal analgesia injection. The
maximum epidural volume of local anaesthetic was 20 ml
per hour in both groups. The infusion rate for PIEB and
PCEA boluses was set at 250 ml.h-1. The women and study
investigators were blinded to group allocation by covering
the PCEA pump with an opaque cover.
The primary outcome measure was the incidence of
breakthrough pain, defined as a VAS score > 30 for which
the parturient requested additional analgesia after
administration of at least one PCEA bolus and local
anaesthetic consumption, defined as milligrams of
ropivacaine used in labour. If breakthrough pain occurred,
the VAS score was noted and an additional manual epidural
top-up bolus of 8 ml of the epidural maintenance local
anaesthetic-opioid solution was administered. After 30 min,
if the VAS score remained > 30, a second top-up bolus of
8 ml of the epidural maintenance solution was given. If the
VAS score remained > 30 after this second top-up dose, the
epidural catheter was considered to have failed. The VAS
scores were recorded every 15 min for 60 min after the
intrathecal injection and then each hour until delivery. Time
of occurrence of breakthrough pain was also recorded.
If patients requested additional analgesia but the
reported VAS score was < 30 mm, breakthrough pain was
not diagnosed and the patient was advised to continue
using the PCEA button.
Secondary endpoints included motor blockade
(modified Bromage score 1–6, every hour) and power; pain
scores; maternal satisfaction scores at 1 h and 24 h
following delivery; PCEA boluses requested and delivered;
time to first PCEA bolus request; duration of labour
following initiation of analgesia; mode of delivery; and
neonatal outcome (1-, 5- and 10-min Apgar scores,
umbilical artery blood gas). See online Supporting
Information Appendix S1 for motor block and power
evaluation. Adverse effects, such as nausea or vomiting,
pruritus and neurologic deficit, occurring during labour and
up to 24 h after delivery, were recorded.
Maternal satisfaction was recorded using a 100-mm
VAS for satisfaction score (0 mm = completely unsatisfied
and 100 mm = extremely satisfied) at 1 h and a numeric
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Anaesthesia 2023, 78, 1129–1138
rating scale (NRS 0–10; 0 = completely unsatisfied and
10 = extremely satisfied) score at 24 h. Baseline patient
characteristics, obstetric and neonatal data were recorded.
The incidence of breakthrough pain and ropivacaine
consumption were defined as co-primary endpoints, setting
a equal to 0.05 for both outcomes. Our previous study
demonstrated that the incidence of breakthrough pain
using PIEB was approximately 10% [17]. We sought to
confirm that high-volume PCEA was non-inferior to PIEB
with respect to breakthrough pain and superior to PIEB with
respect to local anaesthetic consumption. We calculated
the sample size based on the Farrington-Manning score
method, using an upper limit of 10% for the one-sided 95%
CI for the difference in breakthrough pain. To show at least
80% power non-inferiority of PCEA, 122 subjects were
required in each group.
The analgesia intake was compared using a two-sided
independent t-test. With 122 subjects per group and
assuming a standard deviation (SD) of 36 mg for
ropivacaine consumption, the power to detect a difference
of 20 mg was 99%. As a result, even under the worst-case
scenario that the endpoints were not correlated, the
resulting power would still be close to 80% for the
combined endpoints. Since the hypothesis was only
considered proven if both endpoints were met, no
correction for multiple testing for these two primary
endpoints was required. We planned to recruit 140 subjects
per group to allow for dropouts.
A blinded interim analysis for sample size re-estimation
was performed shortly before the end of the recruitment
period to monitor the incidence of breakthrough pain. The
observed incidence of breakthrough pain exceeded the
assumed 10% and an increase in the sample size was
performed to safeguard 80% power. Another 80 patients
were allocated randomly to the two groups. Ultimately, 360
subjects were included in the study.
A multivariable linear model for longitudinal measures
with a heterogeneous compound symmetric covariance
matrix was used to compare the evolution of the VAS scores
over time, restricting the analysis to the first 7 h. Least-
squares means (and their 95%CIs) were reported and
plotted. The Mann–Whitney U-test was used to compare
ordinal or continuous variables between groups. Harrell’s c-
index was used as a measure of effect size, quantifying the
degree of discrimination (c = 0.5 indicates no difference
between both groups). Categorical variables were
compared with Fisher’s exact test and an exact 95%CI was
calculated for the difference.
To compare in an unplanned exploratory analysis of the
within-subject variability of the VAS scores in both groups, a
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linear mixed model (group, categorised time, and their
interaction as fixed effects) with a random intercept and
group-specific residual variances was used and compared
with the same model with restriction to equal residual
variances.
All analyses were performed using SAS software,
version 9.4 (SAS System for Windows, SAS Institute Inc.,
Cary, NC, USA). For the primary outcome, results are
reported on all randomised patients (full analysis set) as well
as on a per-protocol set. All other reported analyses are
restricted to the per protocol set. Women with a failed
epidural catheter who needed epidural catheter
replacement and epidural pump-failures were not included
in the per-protocol analysis.
Results
Between 1 February 2020 and 29 June 2021, 360 women
were recruited into the study (Fig. 1). Each group contained
180 women. Ten patients in the PCEA-group and 14
patients in the PIEB group were not included in the per
protocol set due to discontinuation of the intervention,
yielding 170 and 166 patients in the per-protocol set for
PCEA and PIEB, respectively. Patient characteristics and
baseline obstetric data as well as pain scores at the time of
recruitment are reported in Table 1.
In the per-protocol group, the incidence of
breakthrough pain requiring a top-up dose by an
anaesthetist was 11.2% and 10.8% in the PCEA and PIEB
groups, respectively (Table 2). The upper limit of the one-
sided 95%CI for the difference equalled 6.2%, lower than
the predefined margin of non-inferiority of 10% (p = 0.003),
demonstrating non-inferiority of PCEA to PIEB regarding
breakthrough pain. In the full analysis set, the incidence in
the PCEA group was 2.2 percentage points lower (12.2% vs.
14.4%) and the upper limit of the 95%CI equal to 3.9%
(p < 0.001 for non-inferiority). Ropivacaine consumption
was significantly lower in the PCEA group compared with
the PIEB group in both the per-protocol set (mean
difference 14.6 mg, 95%CI 5.6–23.5 mg, p = 0.002) and
the full analysis set 15.3 mg (95%CI 6.4–24.1, p < 0.001)
(Table 2, Fig. 2). Pain scores were similar between groups,
except for one time-point at 240 min (Fig. 3, Table 3). The
time of breakthrough pain, motor block, patient satisfaction
at 1 h and 24 h after delivery, and incidence of adverse
effects, were similar between groups (Table 2). Obstetric
and neonatal outcomes were not different between the two
groups (Table 4).
An unplanned exploratory analysis revealed that the
within-subject variability starting at 2 h after initiation of
analgesia was significantly higher in the PCEA group
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(p < 0.001). This result was suggested by the differences in
variability (IQR and width of the 95%CI) between groups
(Table 3).
Discussion
Our data demonstrate that PCEA labour analgesia, with
high-volume boluses administered at a similar infusion rate
as PIEB boluses and without a background infusion, is non-
inferior to PIEB. The use of PIEB did not result in less
breakthrough pain, lower pain scores or less motor block
compared with PCEA. Although total local anaesthetic
consumption was increased with PIEB, this did not appear to
be clinically significant. Patient satisfaction was similar
between groups.
Many studies have demonstrated that PCEA is superior
to continuous epidural infusion for maintaining labour
analgesia [3–6]. Programmed intermittent epidural bolus
was introduced into practice almost two decades ago and
trials have compared this with continuous epidural infusion
techniques or PCEA with continuous background infusion
[7–25]. In patients with PIEB, patient satisfaction and quality
of analgesia were superior, motor block was less frequent
and local anaesthetic consumption was reduced [7–25]. In a
2018 Cochrane meta-analysis, the superiority of PIEB to
continuous epidural infusion with or without PCEA was
confirmed [27].
Many institutions still use PCEA with a background
infusion to maintain epidural labour analgesia [5,28].
Halpern and Carvalho demonstrated that the addition of a
low background infusion to a PCEA maintenance technique
improves analgesia because of less breakthrough pain and
fewer physician interventions [5]. A more recent systematic
review by Heesen et al. found that the background infusion
increased the incidence of operative vaginal deliveries and
prolonged the second stage of labour, although the need
for rescue boluses was reduced [28]. The authors concluded
that more research was needed [28]. The studies were
heterogeneous regarding the background infusion rate
(0.5–12 ml.h-1) and PCEA bolus volume (3–10 ml).
The improved local anaesthetic spread in the epidural
space by the administration of a bolus compared with a
continuous infusion has been well demonstrated in the
literature. Cadaveric and experimental models have
suggested that boluses result in wider and more uniform
spread of the drugs in the epidural space compared with a
continuous infusion. Hogan found that the spread of liquids
in the epidural space is highly non-uniform, following
multiple small channels and suggested that the spread is
most uniform when using large bolus volumes and a
correspondingly high injection pressure near the site of
© 2023 Association of Anaesthetists.

Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia
Figure 1 Study flow diagram of patient recruitment.
injection to recruit the most channels [29]. Kaynar and
Shankar compared the spread of solution through a multi-
orifice epidural catheter administered by a bolus and
infusion and found that boluses resulted in wider and more
uniform spread [30]. Mowat et al. showed that at multiple
vertebral levels, bolus administration resulted in a better
spread compared with continuous infusion and a study in
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Anaesthesia 2023, 78, 1129–1138
gynaecological patients also confirmed improved spread
with bolus administration, with more extensive sensory loss
[31, 32]. Because PIEB involves an automated bolus at a
fixed time-interval, this technique offers continuous,
ongoing analgesia, inherent to a continuous epidural
infusion technique, but with improved anaesthetic solution
spread. In contrast, bolus administration that relies on the
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Anaesthesia 2023, 78, 1129–1138 Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia

Table 1 Patient characteristics. Values are mean (SD).

Full analysis set Per-protocol set
PCEA PIEB PCEA PIEB
n = 180 n = 180 n = 170 n = 166
Age; y 29.9 (4.0) 29.6 (3.9) 30.0 (4.0) 29.6 (3.9)
BMI; kg.m2 29.1 (4.9) 29.0 (4.7) 29.1 (5.0) 29.1 (4.7)
Gestational age; weeks 39.2 (1.2) 39.2 (1.2) 39.2 (1.1) 39.3 (1.2)
Cervical dilation at initiation of analgesia; cm 3.7 (1.3) 3.7 (1.3) 3.7 (1.3) 3.7 (1.3)
VAS pain scores immediately before analgesia; 0–100 mm 81.1 (14.1) 81.8 (13.0) 81.0 (14.2) 82.1 (12.8)
PCEA, patient controlled epidural analgesia; PIEB, programmed intermittent epidural bolus; VAS, visual analogue scale (100-mm line
anchored on the left with no pain and right worst pain imaginable).

Table 2 Breakthrough pain and anaesthetic outcome data in the per-protocol group. Values are number (proportion) or
median (IQR [range]). Confidence intervals are two-sided.
PCEA PIEB Effect size
n = 170 n = 166 p value (95%CI)
Incidence of breakthrough pain 19 (11.2%) 18 (10.8%) 0.003 D = 0.3 (-5.6–6.2)a
Total ropivacaine consumption; mg 58 (36–77 [0–324]) 72 (50–96 [12–259]) <0.001 c = 0.63 (0.57–0.69)
Time of breakthrough pain; min 227.5 (177–510 [120–1080]) 182.5 (180–360 [105–804]) 0.590 c = 0.55 (0.36–0.75)
Requested PCEA bolus 7 (4–11 [0–56]) 3 (0–7 [0–50]) <0.001 c = 0.73 (0.67–0.78)
Delivered PCEA bolus 4.5 (3–6 [0–27]) 1 (0–2 [0–8]) <0.001 c = 0.89 (0.86–0.92)
Patient satisfaction VAS score at 100 (90–100 [60–100]) 100 (90–100 [55–100]) 0.803 c = 0.51 (0.45–0.56)
1 h after delivery; 0–100 mm
Patient satisfaction NRS score at 10 (9–10 [6–10]) 10 (9–10 [7–10]) 0.969 c = 0.50 (0.45–0.55)
24 h after delivery; 0–10
Incidence of Bromage score ≤ 4b 4 (2.4%) 6 (3.6%) 0.538 D = -1.3 (-4.9–2.4)
Incidence of Bromage score = 6b 150 (88.4%) 145 (87.4%) 0.868 D = 0.9 (-6.1–7.9)
PCEA, patient-controlled epidural analgesia; PIEB, programmed intermittent epidural bolus; D, absolute risk difference (difference
between groups); c, Harrell’s c-index, quantifying the degree of discrimination (c = 0.5 no difference between both groups, more
specifically the probability that a subject from the one group has a higher value than the subject of the other group); VAS, visual analogue
scale, NRS, numeric rating scale.
a
Evaluation of non-inferiority of PCEA vs. PIEB was based on the one-sided 95%CI (which corresponds with the two-sided 90% CI) and
not on the two-sided 95% CI reported in the rest of this table.
b
6-point modified Bromage scale.

anaesthetist or patient results in analgesia waxes and wanes.
This is consistent with the finding of increased within-group
variability in pain scores in the PCEA group compared with
the PIEB group in the current study.
Active involvement in, and understanding of, a PCEA
regimen by the parturient is essential. In a PCEA-only
setting, analgesia is completely dependent on the patient.
Women are able to titrate analgesic requirements to their
degree of discomfort, which may vary throughout labour
and differ from one patient to another. For those who prefer
greater control over their analgesia, PCEA-only may have a
role. However, when parturients fail to press the button in a
timely manner (e.g. during sleep), breakthrough pain can
occur. By comparison, PIEB maintenance technique
provides less variability in pain compared with a PCEA
maintenance technique. It allows continuous analgesia and
consistent pain relief, and women may not require
additional PCEA boluses.
Several limitations may confound the results of this
study. Maternal satisfaction was high and did not differ
between groups. This may be explained by the fact that when
breakthrough pain did occur, it was immediately treated by
the readily available anaesthetist. Also, because of the hourly
follow-up required by the study protocol, women were
regularly encouraged to press the PCEA button if pain
occurred, encouraging them not to `fall behind´ in
maintaining analgesia. Thus, it is possible that the results of
the study were influenced by the active involvement of study
personnel in the maintenance of analgesia, especially in the
PCEA group. Following implementation of this intervention

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Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia Anaesthesia 2023, 78, 1129–1138

Figure 2 Total ropivacaine consumption in labour (mg) of women in the patient-controlled epidural analgesia (PCEA) and
programmed intermittent epidural bolus (PIEB) groups (full analysis set). The boundaries of the box represent the upper and
lower quartile (the height of the box therefore represents the IQR). The horizontal line in the box and the solid square refer to the
median and mean, respectively. The whiskers refer to the highest observation within 1.5 x IQR from the box. Higher values are
indicated with a dot. An independent t-test (p < 0.001) reported two-sided 95%CIs for the mean (PCEA 63.3 (56.8–69.7) and
PIEB 78.5 (72.4–84.7)) as for the difference in means: -15.3 (-24.1–6.4).

Figure 3 Visual analogue scale (VAS) pain scores over the first 420 min (7 h) following initiation of neuraxial labour analgesia.
Data are mean values obtained from the linear model with vertical lines showing the 95%CI. The VAS pain scores do not differ
between groups, except in one time-point at 240 min (p < 0.001). N is the number of patients in labour in each time
measurement. PIEB group, programmed intermittent epidural bolus (•); PCEA, patient-controlled epidural analgesia group (▪);
*p < 0.001.

in daily clinical practice, large `real world´ studies are In the current study, we used ropivacaine 0.12% with
necessary to understand and investigate the effects of close sufentanil 0.75 lg.ml-1. Many recent studies, however, use
monitoring by study personnel and the absence thereof. even lower concentration solutions [14, 19, 33, 34]. Whether

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Anaesthesia 2023, 78, 1129–1138 Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia

Table 3 Comparison of VAS pain scores at each time-point. Values are median (IQR [range]).
Time (min) PCEA VAS score Estimate (95%CI) PIEB VAS score Estimate (95%CI) p value
0 80 (70–90 [40–100]) 79.6 (77.3–82.0) 80 (75–90 [40–100]) 81.0 (78.6–83.4) >0.999
15 0 (0–20 [0–70]) 1.6 (1.2–2.3) 0 (0–20 [0–85]) 2.3 (1.7–3.1) 0.869
30 0 (0–0 [0–40]) 0.9 (0.6–1.1) 0 (0–5 [0–40]) 1.0 (0.7–1.3) >0.999
45 0 (0–0 [0–50]) 0.8 (0.6–1.1) 0 (0–0 [0–40]) 0.8 (0.6–1.1) >0.999
60 0 (0–0 [0–40]) 0.8 (0.6–1.1) 0 (0–0 [0–50]) 0.7 (0.5–1.0) >0.999
120 0 (0–10 [0–60]) 2.2 (1.6–2.9) 0 (0–10 [0–90]) 1.4 (1.0–1.9) 0.463
180 0 (0–10 [0–80]) 2.1 (1.5–2.8) 0 (0–10 [0–90]) 1.3 (0.9–1.8) 0.463
240 0 (0–20 [0–80]) 3.1 (2.2–4.2) 0 (0–0 [0–80]) 1.0 (0.6–1.5) <0.001
300 0 (0–10 [0–80]) 2.4 (1.6–3.6) 0 (0–10 [0–80]) 1.5 (0.9–2.2) 0.743
360 0 (0–10 [0–80]) 1.7 (1.1–2.6) 0 (0–0 [0–70]) 0.8 (0.4–1.4) 0.366
420 0 (0–10 [0–45]) 1.4 (0.8–2.4) 0 (0–0 [0–50]) 1.2 (0.6–2.1) >0.999
VAS, visual analogue scale; PCEA, patient-controlled epidural analgesia; PIEB, programmed intermittent epidural bolus; Estimate, least-
squares (geometric) mean from a multivariate regression model for longitudinal measures; 95%CI, an inverse hyperbolic sign
transformation was applied to handle the right-skewed distribution of the model residuals, but results are back transformed to the
original scale.
p values are based on the model and are adjusted for multiple testing using a Bonferroni-Holm correction.

Table 4 Obstetric and neonatal outcomes. Values are median (IQR [range]) or number (proportion).
PCEA PIEB Effect size
n = 170 n = 166 p value (95%CI)
Duration of labour; min 321 (221–440 [60–1890]) 350 (234–480 [90–1114]) 0.422 c = 0.53 (0.46–0.59)
Duration of second stage 30 (18–44 [1–93]) 30 (19–45 [2–148]) 0.644 c = 0.52 (0.45–0.58)
labour; min
Spontaneous delivery 110 (64.7%) 96 (57.8%) 0.218 D = 6.9 (-3.5–17.3)
Operative vaginal delivery 39 (22.9%) 39 (23.5%) 1.000 D = -0.6 (-9.6–8.5)
Caesarean delivery 21 (12.4%) 31 (18.7%) 0.132 D = -6.3 (-14.0–1.4)
Total oxytocin dose; IU 1.3 (0.4–2.9 [0–10]) 1.4 (0.2–2.9 [0–10]) 0.899 c = 0.50 (0.44–0.57)
Neonatal weight; g 3384 (3115–3764 [2026–4530]) 3400 (3120–3680 [1825–4780]) 0.626 c = 0.52 (0.45–0.58)
1-min Apgar score 9 (9–9 [1–10]) 9 (8–9 [1–10]) 0.432 c = 0.52 (0.47–0.57)
5-min Apgar < 7 2 (1.2%) 9 (5.4%) 0.034 D = -4.2 (-8.1 to -0.4)
10-min Apgar < 7 1 (0.6%) 0 (0%) 1.000 D = 0.6 (-0.6–1.7)
Umbilical artery pH 7.23 (7.17–7.27 [6.98–7.39]) 7.21 (7.16–7.26 [6.98–7.35]) 0.117 c = 0.55 (0.49–0.62)
PCEA, patient-controlled epidural analgesia; PIEB, programmed intermittent epidural bolus; c, Harrell’s c-index; D, absolute risk
difference (difference between groups).

the use of high- or low-concentration solutions influences
outcomes of the PIEB technique has not been studied.
Although our study was too small to assess safety, PCEA
may be inherently safer than PIEB if a neuraxial catheter is
unintentionally sited in the subarachnoid space [35]. In
contrast, in the setting of an intrathecal catheter and PCEA-
only analgesia maintenance, patients will not self-administer
an additional bolus because they will have no pain. An
additional limitation to our study conclusion is that we
arbitrarily chose the PIEB algorithm that we had used in our
previous study, and that is used clinically in our institutions.
It is possible that different pump setting (i.e. bolus volume,
bolus interval, bolus infusion rate) might influence the
results and conclusions [36–43].
We have demonstrated that a PCEA high-volume bolus
without a background infusion is not inferior to PIEB for
maintenance of epidural labour analgesia and superior
regarding local anaesthetic consumption. The results of the
study support the use of high-volume bolus techniques,
whether as part of PIEB or PCEA, for the maintenance of
epidural labour analgesia. The PIEB techniques provide
more consistent pain control (less variability), whereas
PCEA-only may give women more control over their
analgesia.

1136 © 2023 Association of Anaesthetists.


Roofthooft et al. | Patient-controlled epidural vs. programmed intermittent epidural bolus for labour analgesia
Acknowledgements
The study was registered at the Belgian Federal Agency for
Medicines and Health Products (EudraCT 2019-003319-76).
The study was, in part, supported by a research grant from
the Belgian Association of Regional Anesthesia and the
Obstetric Anaesthetists’ Association and by departmental
funding of the Department of Cardiovascular Sciences,
Anaesthesia Department at the KU Leuven, Belgium. MV has
received financial support for lectures and consultancy from
Smiths Medical (producer of PIEB pumps) and is receiving
financial compensation for lectures and consultancy
from CSL Behring, Sintetica, Grunenthal, Ferrer, Nordic
Pharma, MSD, HeronTx, Halyard, Flatmedical, Aquettant,
Viforpharma and Medtronic, but there was no involvement
of any industry in any aspect of the study. We thank Ms C.
Huyghens and the midwives of the department of Leuven
and St Augustinus Antwerp for their contribution to the
study. No other competing interests declared.
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Supporting Information
Additional supporting information may be found online via
the journal website.
Appendix S1. Motor block and power evaluation
© 2023 Association of Anaesthetists.