Open Journal of Anesthesiology, 2013, 3, 379-382
Published Online November 2013 (http://www.scirp.org/journal/ojanes)
http://dx.doi.org/10.4236/ojanes.2013.39080
Open Access OJAnes
379
Comparison between 0.06% and 0.1% Levobupivacaine
Combined with 2 μg/mL of Fentanyl for Epidural Labor
Analgesia
Takako Hamada, Mariko Baba, Masaki Sato, Takayuki Saito, Keisuke Murakami,
Hiroyuki Sumikura*
Obstetric Anesthesia Department, National Center for Child Health and Development, Tokyo, Japan.
Received September 9th, 2013; revised September 27th, 2013; accepted October 8th, 2013
Copyright © 2013 Takako Hamada et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Purpose: Levobupivacaine is thought to be a good alternative to bupivacaine for epidural labor analgesia because of its
pharmacologic profile. However, the optimal concentration of levobupivacaine for labor analgesia has not been ade-
quately studied. The objective of this retrospective study was to compare the analgesic effect of levobupivacaine be-
tween 0.06% and 0.1% both combined with 2 μg/mL of fentanyl. Methods: Primiparous women (ASA I, II) who deliv-
ered their babies to our hospital using combined spinal epidural analgesia and patient-controlled epidural analgesia be-
tween August 1, 2011 and September 30, 2011 were included into this retrospective study. The analgesic solution for
epidural administration was 0.06% levobupivacaine with 2 μg/mL of fentanyl between August 1 and 31, and 0.1%
levobupivacaine with 2 μg/mL of fentanyl between September 1 and 30. Their anesthetic and obstetric charts were re-
viewed to compare obstetric outcome, anesthetic intervention, and patients’ satisfaction. Results: There were 46 women
fulfilling the inclusion criteria: 23 women in 0.06% group, and 23 women in 0.1% group. The number of patients who
needed more than 3 requests for one actual bolus was significantly higher in the 0.06% group (P < 0.05). Conclusion:
Our results revealed that 0.06% levobupivacaine combined with 2 μg/mL fentanyl does not provide sufficient analgesic
effects for epidural labor analgesia. It seems that levobupivacaine has not been adequately studied after its withdrawal
from the US market. Further studies should be conducted to determine the optimal concentration of levobupivacaine for
epidural labor analgesia.
Keywords: PCEA; CSEA; Labor Analgesia; Levobupivacaine
1. Introduction
Levobupivacaine is a pure S(−) enantiomer of racemic
bupivacaine, whereas bupivacaine consists of both an S(–)
enantiomer and R(+) enantiomer [1,2]. Levobupivacaine
is thought to be a good alternative to racemic bupiva-
caine for epidural labor analgesia because the S(−) enan-
tiomer has less affinity for the sodium channels and thus
has fewer depressant effects on the cardiovascular and
central nervous systems than the R(+) enantiomer. How-
ever, the optimal concentration of levobupivacaine for la-
bor analgesia has not been adequately studied.
At the National Center for Child Health and Develop-
ment, where combined spinal epidural analgesia (CSEA)
followed by patient-controlled epidural analgesia (PCEA)
has been adopted as a standard technique for labor anal-
gesia, a combination of 0.1% ropivacaine with 2 μg/mL
of fentanyl had been used effectively as a PCEA solution
until the end of July in 2011. However, our pharmaceu-
tical department needed to reduce the number of items of
local anesthetics, and decided to delete ropivacaine from
the list for regular stock. Hence, we had to change the lo-
cal anesthetic for labor analgesia from ropivacaine to le-
vobupivacaine.
Although levobupivacaine has been used for labor an-
algesia in some countries [3], we found that an optimal
concentration of levobupivacaine has not been well stud-
ied by reviewing textbooks and literatures describing
levobupivacaine for epidural labor analgesia. Therefore
*Corresponding author.

Comparison between 0.06% and 0.1% Levobupivacaine Combined with
2 μg/mL of Fentanyl for Epidural Labor Analgesia
380
we hastened to start with 0.06% levobupivacaine with 2
μg/mL of fentanyl, as it had been reported that minimum
anesthetic concentration of bupivacaine and levobupiva-
caine were similar to each other, and 0.06% of bupiva-
caine had been successfully used for labor analgesia by
combining with fenatnyl.
After one month experience with 0.06% levobupiva-
caine with 2 μg/mL of fentanyl, we noticed an increased
number of patients requiring anesthesiologist’s interven-
tion for rescue treatment, and decided to inspissate PCEA
solution to 0.1% levobupivacaine with 2 μg/mL of fen-
tanyl. Another one month experience with new solution
convinced us that the number of patient with insufficient
pain relief decreased. The purpose of this retrospective
study was to compare the number of patients with in-
sufficient pain control during their delivery between dif-
ferent concentrations of levobupivacaine (0.1% versus
0.06%), both combined with 2 μg/mL of fentanyl.
2. Material and Methods
A list of deliveries between August 1, 2011 and Septem-
ber 30, 2011 was checked to extract primiparous women
(ASA I, II) who delivered their baby at our hospital using
combined spinal epidural analgesia and patient-controlled
epidural analgesia. Their anesthetic and obstetric charts
were reviewed to compare obstetric outcome, anesthetic
intervention, and patients’ satisfaction. Parturient who
delivered their babies within 2 hours after the intrathecal
administration were excluded from the study because of
the potentially limited effects of PCEA.
During the time period of the study, the following
standard protocol was used for labor analgesia. When a
patient requested pain relief, analgesia was begun with an
intrathecal administration of 2.5 mg of hyperbaric bupi-
vacaine and 10 μg of fentanyl. An indwelling epidural
catheter was placed simultaneously and connected to
PCEA device, which was set as 5 mL for bolus dose, 15
minutes for lockout interval and no background infusion.
The analgesic solution for epidural administration was
0.06% levobupivacaine with 2 μg/mL of fentanyl be-
tween August 1 and 31, and 0.1% levobupivacaine with 2
μg/mL of fentanyl between September 1 and 30. To make
up a transition from spinal analgesia to epidural analgesia
smoothly, the first and second epidural bolus administra-
tion was instructed by anesthesiologists around 20 and 40
minutes after the intrathecal administration. After these
instructed boluses, a PCEA button was given to the pa-
tient so that she could request additional pain relief as
needed. If the analgesic effect was not sufficient, a rescue
dose of anesthetics (PCEA solution, lidocaine, or fen-
tanyl) was administered at the discretion of the anesthe-
siologist. The postnatal visit was done by an attending
anesthesiologist, and the patient’s satisfaction was evalu-
ated and classified into 5 grades (very good, good, fair,
bad, and very bad).
Patients’ background and obstetric outcomes were
checked from obstetric charts, whereas number of PCEA
request and administered boluses, anesthesiologists’ in-
tervention for breakthrough pain and patients’ satisfac-
tion were checked from anesthetic charts.
The differences in continuous variables were analyzed
by student’s t-test, and data were presented as mean
±standard deviation. Differences in categorical variables
were analyzed by the chi-square test, and data were pre-
sented in real numbers. A P-value of <0.05 was consid-
ered to be significant. As the study was conducted retro-
spectively, an informed consent was not obtained from
the patients for this specific study. However, all patients
had consented on admission to having their clinical data
used for publication as an upfront consent, and our insti-
tutional review board approved this consent for publica-
tion of the study.
3. Results
There were 46 women fulfilling the inclusion criteria: 23
women with 0.06% levobupivacaine combined with 2
μg/mL of fentanyl (0.06% group), and 23 women with
0.1% levobupivacaine combined with 2 μg/mL of fen-
tanyl (0.1% group).
No significant differences were found between the
groups in patient characteristics, duration of labor, mode
of delivery, or Apgar-score (Table 1). The number of pa-
tients who needed more than 3 requests for an actual bo-
lus was significantly higher (P < 0.05) in the 0.06%
Table 1. Patient characteristics, duration of delivery, mode
of delivery, and APGAR scores.
0.1% Group
(n = 23)
0.06% Group
(n = 23)
Age 36.4 (+/− 5.3) 36.9 (+/− 4.2)
Height 159.5 (+/− 5.1) 160.8 (+/− 5.4)
Weight 61.4 (+/− 6.7) 60.9 (+/− 7.7)
Patient
Characteristics
Gestational
weeks 39.2 (+/− 1.4) 39.4 (+/− 1.2)
1st stage 613.5 (+/− 263.9) 747.0 (+/− 297.1)
Duration of
delivery 2nd stage149.0 (+/− 61.6) 129.4 (+/− 68.5)
Spontaneous8 8
Instrument14 11
Mode of
delivery
Cesarean
section 1 4
1 min 8 (1 - 9) 8 (4 - 9)
APGAR score
5 min 9 (7 - 10) 9 (8 - 9)
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Comparison between 0.06% and 0.1% Levobupivacaine Combined with
2 μg/mL of Fentanyl for Epidural Labor Analgesia
381
group (Table 2). However, there was no difference in pa-
tient satisfaction between the groups (Table 3).
4. Discussion
Because of its pharmacologic profile, levobupivacaine
has been considered to be a suitable anesthetic agent for
epidural labor analgesia. However, we could find only
one study that compared different concentrations of levo-
bupivacaine for its analgesic effects in epidural analgesia.
Tixier and colleagues [4] compared two different con-
centrations of levobupivacaine (0.0625% and 0.125%)
both combined with 5 μg/mL of sufentanil, and found
that the 0.125% concentration provided better analgesic
effects. However, the use of 0.125% of levobupivacaine
was associated with a risk of overdosing, and they in-
sisted that a lower concentration of the agent between the
two concentrations they studied should be studied for
better analgesic effect and lower risk of overdosing. In
the present study comparing two concentrations lower
than they suggested, we found that 0.1% levobupivacaine
combined with 2 μg/mL of fentanyl provided better an-
algesic effects than 0.06% levobupivacaine with 2 μg/mL
of fentanyl.
Considering an effect of concentration, it is not sur-
Table 2. Number of patients at bad control and unschedu-
led interventions.
0.1% Group 0.06% Group
Number of patients needed
> 2 requests for one bolus 12 15
Number of patients needed
> 3 requests for one bolus 6 13*
0 17 12
1 2 5
2 3 2
3 1 1
4 0 0
Number of
intervention by
anesthesiologists
5 or more 0 3
*P < 0.05.
Table 3. Patient satisfaction.
0.1% Group 0.06% Group
Very good 4 3
Good 8 14
Fair 10 4
Bad 1 2
Patient
satisfaction
Very bad 0 0
prising that 0.1% levobupivacaine provided a better an-
algesic effect than 0.06% levobupivacaine. However, an
analgesic effect of 0.06% levobupivacaine with 2 μg/mL
of fentanyl. was somewhat betraying our expectations, as
0.06% bupivacaine, which has a minimum local analge-
sic concentration (MLAC) similar to that of levobupiva-
caine [5], has been widely used for epidural labor anal-
gesia in combination with opioid.
The MLACs of various anesthetics have been previ-
ously calculated [6]: bupivacaine, 0.081% [5,7-11]; levo-
bupivacaine, 0.083% [5,12,13]; and ropivacaine, 0.11%
[8,12-15]. Based on these calculations, 0.1% ropivacaine
is assumed to be equipotent to 0.07% levobupivacaine
because the MLAC of levobupivacaine is approximately
70% of that of ropivacaine. Therefore, we were aware
that the analgesic effect would be decreased to some ex-
tent after changing the analgesic for PCEA from 0.1%
ropivacaine with 2 μg/mL of fentanyl to 0.06% levobupi-
vacaine with 2 μg/mL of fentanyl. However, the analge-
sic effect decreased more than we predicted so that after
one month, we had to increase the concentration of levo-
bupivacaine to 0.1%. This change was considered enough
to provide sufficient analgesic effects for most patients.
Results of a study by Lee and colleagues [16] also sug-
gested that 0.06% levobupivacaine might not provide
sufficient analgesic effects even in combination with
opioid analgesics. They compared 0.06% levobupivacaine
and 0.08% ropivacaine, which were expected to be equi-
potent [6] (both were combined with 2 μg/mL of fen-
tanyl). Their results showed that the levobupivacaine
group required rescue for breakthrough pain significantly
more often than the ropivacaine group [16]. Our findings
are consistent with their report that 0.06% levobupiva-
caine combined with opioid could not provide sufficient
pain relief for labor analgesia. Recent studies that evalu-
ated the MLAC of levobupivacaine and ropivacaine si-
multaneously reported very similar values of MLAC
[12,13,17,18]. Therefore it seems that levobupivacaine
should be used in the same concentration as ropivacaine,
not as bupivacaine.
As the study was not a randomized control study, the
result might be biased by our expectation and experience.
Furthermore, an insufficient analgesic effect of 0.06%
ropivacaine could be covered by increasing the bolus
dose or shortening the lockout interval. However, we still
feel worthy enough to report the result, as few reports
exist about the optimal concentration of levobupivacaine
for epidural labor analgesia. The scares data of levobu-
pivacaine for labor analgesia may be attributable to the
fact that levobupivacaine was withdrawn from the US
market [17]. In conclusion, our results revealed that
0.06% levobupivacaine combined with 2 μg/mL fen-
tanyl does not provide sufficient analgesic effects for
Open Access OJAnes

Comparison between 0.06% and 0.1% Levobupivacaine Combined with
2 μg/mL of Fentanyl for Epidural Labor Analgesia
Open Access OJAnes
382
epidural labor analgesia. Further studies should be con-
ducted to determine the optimal concentration of levobu-
pivacaine for epidural labor analgesia.
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