Comparison between 0.06% and 0.1% Levobupivacaine Combined with 2 μg/mL of Fentanyl for Epidural Labor Analgesia

doi:10.4236/ojanes.2013.39080

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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.

Email: *[email protected]

Received September 9th, 2013; revised September 27th, 2013; accepted October 8th, 2013

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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