A Comparison of Epidural Bupivacaine, Levobupivacaine, and ...

PEDIATRIC ANESTHESIA SOCIETY FOR PEDIATRIC ANESTHESIA
SECTION EDITOR
WILLIAM J. GREELEY
A Comparison of Epidural Bupivacaine, Levobupivacaine, and
Ropivacaine on Postoperative Analgesia and Motor Blockade
Pasquale De Negri, MD*, Giorgio Ivani, MD†, Tiziana Tirri, MD*, Pasqualina Modano, MD*,
Cesare Reato, MD*, Staffan Eksborg, PhD‡, and Per-Arne Lonnqvist, MD, PhD‡
*Department of Anesthesia, ICU and Pain Management, Centro di Riferimento Oncologico della Basilicata-Cancer Center,
Rionero in Vulture, Potenza, Italy; †Department of Pediatric Anesthesia and Intensive Care Unit, “Regina Margherita”
Children’s Hospital, Turin, Italy; and ‡Department of Women and Child Health and Department of Surgical Sciences,
Karolinska Institute, Stockholm, Sweden
In this prospective, randomized, observer-blinded clinical
trial, we compared the incidence of unwanted
lower extremity motor blockade and the analgesic efficacy
between small-dose (0.125%; 0.2 mg · kg 1 ·h 1 )
postoperative epidural infusions of bupivacaine
(Group B; n 28), levobupivacaine (Group L; n 27),
and ropivacaine (Group R; n 26) in children after hypospadias
repair. Motor blockade and pain were assessed
at predetermined time points during 48 h by using
a modified Bromage scale and the Children’s and
Infant’s Postoperative Pain Scale (CHIPPS). Postoperative
analgesia was almost identical in all three study
groups (CHIPPS range, 0–3), with no need for the
Bupivacaine has, until recently, been the drug of
choice for postoperative epidural infusions in
children. Despite a reasonable safety profile, bupivacaine
is currently being replaced by many anesthesiologists
with new local anesthetics: levobupivacaine
and ropivacaine. These local anesthetics are
associated with less risk for cardiac and central nervous
system toxicity and are also less likely to result in
unwanted postoperative motor blockade (1,2). Despite
numerous publications with regard to the use of
levobupivacaine and ropivacaine in children, no randomized
studies have compared the use of these three
drugs for continuous postoperative epidural infusion.
Thus, the aim of this investigation was to compare the
effect of a continuous postoperative epidural infusion
of these three local anesthetic drugs on motor blockade
and pain relief after hypospadias repair.
Accepted for publication January 16, 2004.
Address correspondence to Pasquale De Negri, MD, Department
of Anesthesia, ICU and Pain Management, CROB-Cancer Center,
Strada Provinciale del Vulture 8, Rionero in Vulture (PZ), 85028,
Italy. Address e-mail to pdenegri@crob.it. Reprints will not be available
from the authors.
DOI: 10.1213/01.ANE.0000120162.42025.D0
administration of supplemental analgesia in any patient.
However, significantly more patients in Group B
(n 6; P 0.03) displayed signs of unwanted motor
blockade during the observation period compared with
Group L (n 0) and Group R (n 0). In conclusion,
significantly less unwanted motor blockade was associated
with postoperative epidural infusions of 0.125%
levobupivacaine or ropivacaine in children after hypospadias
repair as compared with a similar infusion of
bupivacaine. However, no difference with regard to
postoperative analgesia could be detected among the
three different local anesthetics studied.
(Anesth Analg 2004;99:45–8)
Methods
After IRB approval and written, informed parental consent,
90 boys (2–6 yr of age; ASA status I) scheduled for
hypospadias repair were included in this prospective,
randomized study. All patients received oral premedication
with midazolam 0.5 mg/kg approximately 45 min
before arrival in the operating room. After standard noninvasive
monitoring was applied, general anesthesia was
induced with sevoflurane 8% by face mask. After the
induction of anesthesia, the airway was managed either
by a laryngeal mask airway or by endotracheal intubation
(facilitated by atracurium 0.5 mg/kg). Anesthesia
was thereafter maintained with isoflurane 0.8%–1% in an
oxygen/air mixture throughout the remaining part of
the procedure.
With the patient in the lateral decubitus position, an
epidural catheter (Portex 19-gauge epidural kit) was
placed at the L5-S1 level by using a loss-of-resistance
technique. The catheter was threaded approximately 3
cm in the caudal direction. After placement of the
epidural catheter, all patients received incremental injections
of 0.2% ropivacaine up to a total dose of
1.4 mg/kg while they were watched for signs of toxicity
(no epinephrine-containing test dose was used).
©2004 by the International Anesthesia Research Society
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EPIDURAL LOCAL ANESTHESIA INFUSIONS IN CHILDREN 2004;99:45–8
The maximum volume of ropivacaine was 20 mL. The
patient was then prepared, and surgery was allowed
to commence. The block was judged as successful if
there was no or a only minor (15% increase) hemodynamic
reaction (heart rate, noninvasive arterial
blood pressure, or both) to the start of surgery. Sixty
minutes after the initial epidural injection, a continuous
infusion of plain ropivacaine 0.125% was started
at a rate of 0.2 mg · kg 1 · h 1 and was continued for
the duration of the surgical procedure.
After emergence from the anesthetic, patients were
transferred to the recovery area. Immediately after arrival
to the recovery room, patients received, according
to the previous randomization, 1 of 3 different epidural
infusions—levobupivacaine 0.125% 0.2 mg · kg 1 · h 1
(group L), ropivacaine 0.125% 0.2 mg · kg 1 · h 1 (group
R), or bupivacaine 0.125% 0.2 mg · kg 1 · h 1 (group
B)—for 48 h. The infusions were prepared, given a code
number, and connected to the patient by an operator
who took no further part in the study.
Postoperative analgesia (Fig. 1) and the degree of motor
blockade were assessed every 4 h throughout the first
48 postoperative hours. Analgesia was assessed by using
the Children’s and Infant’s Postoperative Pain Scale
(CHIPPS) (3), and the degree of motor blockade was
recorded by using a modified Bromage scale (4). Trained
nurses unaware of the randomization performed all the
postoperative assessments.
Patients were not prescribed any postoperative analgesics
apart from the epidural infusion. Rescue analgesia
with acetaminophen-codeine suppositories
(200 mg/5 mg) was administered according to patient
weight if the CHIPPS score was 4. The time to first
need for rescue analgesia and the total amount of
supplemental analgesics were also recorded during
the 48-h observation period.
Statistical analysis was performed by nonparametric
tests as appropriate, and P values 0.05 were considered
significant. On the basis of pilot data, the
study was designed to be able to detect a 15% difference
between study groups with regard to the number
of patients with an absence (score 0) or presence (score
1–3) of motor blockade during the postoperative period.
A power calculation based on these assumptions
together with an of 0.05 and a of 0.8 resulted in the
need for 25 patients in each treatment group.
Results
A total of 90 patients were included in the study. Two
patients in group B, three patients in group L, and four
patients in group R were excluded from the analysis
because of an inadequate block or modification of the
planned surgery after inclusion in the study. Thus, the
final number of patients in each group was 28, 27, and
26 for groups B, L, and R, respectively. Patient demographics
and other basic data are displayed in Table 1.
Figure 1. Mean CHIPPS scores for the first 48 postoperative hours.
A CHIPPS score exceeding 3 indicated a need for supplemental
rescue analgesia. Levo levobupivacaine; bupi bupivacaine; ropi
ropivacaine.
None of the patients displayed any signs of motor
blockade during the first 12 h of infusion. Only patients
in group B displayed signs of motor blockade
during the 12- to 48-h postoperative period. Thus, 6
patients in group B had motor block scores of 1 or
2 during the postoperative period, a finding that was
significantly higher compared with both group L (P
0.03) and group R (P 0.03). None of the patients had
a motor block score of 3. If expressed as 95% confidence
intervals for the occurrence of unwanted postoperative
motor block (percentage of patients) these
95% confidence intervals were 0%–10%, 0%–11%, and
8%–41% for groups L, R, and B, respectively.
No significant difference among groups could be
observed at any of the observation points during the 0to
48-h postoperative period with regard to CHIPPS
score (Fig. 1). Because none of the patients had a
CHIPPS score of 4, no supplemental analgesia was
administered in any of the study groups. No other
side effects were noted in any patient during the study
period.
Discussion
The main finding of this study was that epidural infusions
of 0.125% solutions of bupivacaine, levobupivacaine,
or ropivacaine resulted in almost identical
postoperative analgesia after hypospadias repair in
children. No signs of postoperative motor blockade
were observed in patients given levobupivacaine or
ropivacaine, whereas bupivacaine caused minor to
moderate postoperative motor block in approximately
20% of the patients.
The primary aim of this study was to evaluate
whether postoperative epidural infusions of the studied
local anesthetics were associated with the occurrence
of unwanted motor blockade. To allow this, we
had to avoid a situation in which the intraoperative

ANESTH ANALG PEDIATRIC ANESTHESIA DE NEGRI ET AL. 47
2004;99:45–8 EPIDURAL LOCAL ANESTHESIA INFUSIONS IN CHILDREN
Table 1. Patient Data
Variable
activation of the epidural blockade by a bolus injection
of local anesthetics would confound the baseline situation
after surgery. A different design might have
caused a situation in which some patients had unwanted
motor blockade immediately after surgery.
Because caudal bolus injection of 0.2% ropivacaine in
children has not been associated with motor blockade
(4–6), and because ropivacaine (based on minimal
local anesthetic concentrations [MLAC] studies) is regarded
as less potent than bupivacaine (7,8), we decided
to activate the epidural blockade during surgery
with 0.2% ropivacaine in all patients. The observation
that all patients had a motor block score of 0 in the
recovery room verifies that this study design achieved
the objective of producing a baseline situation with no
signs of unwanted motor blockade in any patient.
Our finding of a significantly more frequent incidence
of motor blockade with the use of 0.125% bupivacaine
infusion versus similar concentrations of levobupivacaine
or ropivacaine is in keeping with previous reports
of a better discrepancy between analgesia and motor
blockade for the new long-acting local anesthetics in
adults (1,2). The present finding is also similar to our
previously reported data after single-injection caudal
blockade in children, where the use of 0.25% bupivacaine
caused a more frequent incidence of motor blockade
compared with 0.25% levobupivacaine or 0.2%
ropivacaine (4). This difference between bupivacaine
on one hand and levobupivacaine and ropivacaine on
the other was still present in the current study despite
the use of more dilute local anesthetic solutions for
continuous epidural infusion.
The incidence of unwanted motor blockade associated
with the use of bupivacaine could most likely be
eliminated if even smaller concentrations were used,
but a previous study by Wolf et al. (9) showed that
such dilute bupivacaine solutions are associated with
an unreliable analgesic effect. Thus, either of the two
new long-acting local anesthetics should be used for
postoperative epidural infusion instead of bupivacaine
to minimize the risk for unwanted postoperative
motor blockade in children.
In keeping with previous pediatric studies (4–6,10–
12), we were unable to identify any difference with
regard to postoperative analgesia among the three
different local anesthetics used, despite using only
0.125% concentrations of each drug. This observation
was true concerning both CHIPPS scores and the need
for supplemental postoperative analgesia. Thus, from
a clinical perspective, the 0.125% concentration of the
3 studied local anesthetics appears equipotent with
regard to postoperative analgesia after epidural infusion
in children.
As noted above, ropivacaine has been claimed to
possess only 60% of the analgesic potency of bupivacaine
on the basis of findings generated in MLAC
studies (7,8). However, the generalization of potency
data from MLAC studies has been questioned because
of the specific circumstances associated with obstetric
epidural analgesia and because of the scientific design
of MLAC studies.
In summary, significantly less unwanted motor
blockade was associated with postoperative epidural
infusions of 0.125% levobupivacaine or ropivacaine in
children after hypospadias repair as compared with a
similar infusion of bupivacaine. No difference with
regard to postoperative analgesia could be detected
among the three different local anesthetics studied.
References
Group
Levobupivacaine Ropivacaine Bupivacaine
No. Patients 27 26 28
ASA physical status I I I
Age (mo) 29 10 30 8 27 16
Weight (kg) 14 6 15 4 14 7
Preoperative heart rate (bpm) 103 11 107 4 106 9
Preoperative systolic NIBP (mm Hg) 85 5 82 7 83 6
Postoperative heart rate (bpm), 0–24 h 105 7 104 6 108 7
Postoperative systolic NIBP (mm Hg), 0–24 h 90 7 92 8 87 6
NIBP noninvasive blood pressure.
Data are displayed as mean sd.
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