Relative Analgesic Potencies of Levobupivacaine and
Ropivacaine for Caudal Anesthesia in Children
Pablo Ingelmo, MD*
Geoff Frawley, MD†
Marinella Astuto, MD*
Chris Duffy, MD†
Susan Donath, PhD‡
Nicola Disma, MD§
Giuseppe Rosano, MD§
Roberto Fumagalli, MD*
Antonio Gullo, MD§
BACKGROUND: Comparing relative potency of new local anesthetics, such as
levobupivacaine and ropivacaine, by the minimum local analgesic concentration
model has not been described for caudal anesthesia. Therefore, we performed a
prospective, randomized, double-blind study to determine the minimum local
analgesic concentrations of a caudal single shot of ropivacaine and levobupivacaine
in children and to describe the upper dose-response curve.
METHODS: We performed a two-stage prospective, randomized, double-blind study
comparing the dose-response curves of caudal ropivacaine and levobupivacaine in
children. In phase 1, 80 boys were randomized to receive either ropivacaine or
levobupivacaine. In the second phase a further 32 patients were randomly allocated
to receive caudal anesthesia with doses designed to delineate the upper dose-
response range (the 50% effective dose [ED
50
]–ED
95
range).
RESULTS: There were no significant differences in ED
50
values for caudal ropivacaine
and levobupivacaine. The ED
50
for levobupivacaine estimated from the Dixon
Massey method was 0.069% (95% CI 0.056%– 0.082%) and for ropivacaine was
0.075% (95% CI 0.058%– 0.092%). Estimated by isotonic regression the ED
50
and
ED
95
respectively of levobupivacaine were 0.068 (0.04 – 0.09) and 0.20% (95% CI
0.16%– 0.24%). For ropivacaine ED 50 and ED95 were 0.066 (0.033– 0.098) and
0.225% (95% CI 0.21%– 0.24%).
CONCLUSIONS: In children receiving one minimum alveolar anesthetic concentration
of sevoflurane, there were no significant differences in the ED
50
for caudal
levobupivacaine and ropivacaine. The potency ratio at ED
50
was 0.92 and 0.89 at
ED
95
, indicating that caudal levobupivacaine and ropivacaine have a similar
potency.
(Anesth Analg 2009;108:805–13)
An efficient way to compare the potency of new
long-acting local anesthetics such as levobupivacaine
and ropivacaine in a clinical setting is to determine the
minimum effective local anesthetic concentration (MLAC)
required to produce adequate pain relief in 50% of
patients (the Dixon Massey Up-Down sequential allo-
cation technique).
1
Adult studies comparing the mini-
mum local analgesic concentrations of levobupivacaine
and ropivacaine have reported conflicting results.
2– 4
Stud-
ies in obstetric patients based on up-down sequential
allocation designs have suggested that ropivacaine is
less potent than racemic bupivacaine.
4,5
However,
some studies have determined that ropivacaine and
bupivacaine are equipotent and that although their
50% effective dose (ED
50
) may vary, the dose-response
curves overlap at clinically relevant doses.
6
For epi-
durally administered surgical anesthesia, ropivacaine
and bupivacaine have essentially similar sensory and
motor block profiles but with intrathecal studies
sensory-motor separation is more marked.
6,7
To determine the dose-response relationship re-
quires information on the ED
50
(MLAC), the slope of
the dose-response curve and the maximal efficacy.
Deng et al.
8
reported an ED
50
of ropivacaine, but the
MLAC of caudal levobupivacaine has not been de-
scribed in children and little is known about the upper
dose-response curve of either drug. The MLAC method
provides accurate estimation of the ED
50
for a certain
response but does not allow for interpretation of the
whole dose-response curve. Although imprecise ex-
trapolation of data to provide the ED
95
dose using
logistic regression analysis after probit transformation
has been reported. It is important to have more detail
about the upper dose-response range for pediatric
From the *Department of Perioperative Medicine and Intensive,
A.O. San Gerardo, Monza, Dipartimento di medicina sperimentale
ambientale e biotecnologie mediche, Universita ` degli Studi Milano
Bicocca, Milan, Italy; †Department of Paediatric Anesthesia and
Pain Management, Royal Children’s Hospital. Melbourne Australia;
‡Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s
Research Institute, University of Melbourne Australia; and §Depart-
ment of Anesthesia, A.O.U. Policlinico Catania, Universita ` degli
Studi di Catania, Italy.
Accepted for publication September 2, 2008.
Supported by the Department of Perioperative Medicine and
Intensive, A.O. San Gerardo and by the Department of Anesthesia,
A.O.U. Policlinico Catania.
Address correspondence and reprint requests to Dr. Geoff
Frawley, Department of Paediatric Anesthesia and Pain Manage-
ment, Royal Children’s Hospital, Melbourne Australia. Address
e-mail to geoff.frawley@rch.org.au.
Copyright © 2009 International Anesthesia Research Society
DOI: 10.1213/ane.0b013e3181935aa5
Vol. 108, No. 3, March 2009 805