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Original Contributions

Clinical Properties of
Levobupivacaine or Racemic
Bupivacaine for Sciatic
Nerve Block
Andrea Casati, MD,* Jacques E. Chelly, MD, PhD,
Elisa Cerchierini, MD, Roberta Santorsola, MD,*
Fiorella Nobili, MD,* Crispino Grispigni, MD,
Pia Di Benedetto, MD, Giorgio Torri, MD
Vita-Salute University, Department of Anesthesiology, IRCCS H. San Raffaele, Milan,
Italy; Department of Anesthesiology, University of Texas Medical School at Houston,
Houston, TX; Department of Anesthesiology, CTO Roma, Rome, Italy

Study Objective: To compare the intraoperative and postoperative clinical properties of


*Staff Anesthesiologist, Vita-Salute University the sciatic nerve block performed with either 0.5% bupivacaine or 0.5% levobupivacaine
Department of Anesthesiology, IRCCS H San for orthopedic foot procedures.
Raffaele, Milan, Italy Design: Randomized, double-blind study.
Professor, Director of Clinical Research in Setting: Inpatient unit of a university-affiliated hospital.
Orthopedic Pain, University of Texas Medi- Patients: 30 ASA physical status I and II patients undergoing elective hallux valgus
cal School at Houston, Houston, Texas repair under regional anesthesia.
Fellow in Anesthesiology, Vita-Salute Uni- Interventions: After administering intravenous (IV) midazolam premedication (0.05
versity Department of Anesthesiology, IRCCS mg/kg), a femoral nerve block was performed with 15 mL of mepivacaine 2%. Patients
H San Raffaele, Milan, Italy were then randomly allocated to receive, in a double-blind fashion, a sciatic nerve block
Staff Orthopedic Surgeon, Vita-Salute Uni- with 20 mL of either 0.5% bupivacaine (n 15) or 0.5% levobupivacaine (n 15).
verity Department of Orthopedic Surgery, Measurements and Main Results: An observer who was blinded to the study drug
IRCCS H Raffaele, Milan, Italy recorded the onset time, quality, and duration of the sciatic nerve block. Postoperative
Staff Anesthesiologist, CTO Roma, Rome,
analgesia consisted of 100 mg IV ketoprofen every 8 hours, with the first administration
Italy given at the patients request. Mean (SEM) onset time of the sciatic nerve block was 35
5 minutes for bupivacaine and 31 6 minutes for levobupivacaine (p not significant
Professor of Anesthesiology, Vita-Salute Uni-
[NS]). The duration of motor and sensory blocks with bupivacaine was 761 112
versity Department of Anesthesiology, IRCCS
H San Raffaele, Milan, Italy minutes and 790 110 minutes, respectively, and 716 80 minutes and 814 73
minutes, respectively, with levobupivacaine (p NS). The first pain medication was
Address correspondence to Dr. Casati at the requested after 844 96 minutes with bupivacaine and 872 75 minutes after
Department of Anesthesiology, IRCCS H San
levobupivacaine (p NS). No differences in the quality of nerve block and patient
Raffaele, Via Olgettina 60, 20132 Milan, Italy.
E-mail: casati.andrea@hsr.it satisfaction were reported between the two groups.
Conclusions: A dose of 20 mL of 0.5% levobupivacaine induces sciatic nerve block of
Abbott SpA, Rome, Italy, provided the
similar onset, duration, and intensity as the block produced by the same volume and
levobupivacaine for this study.
concentration of the racemic solution of bupivacaine. 2002 by Elsevier Science Inc.
Received for publication June 29, 2001; re-
vised manuscript accepted for publication Keywords: Anesthetic techniques, regional: sciatic nerve block; anesthetic,
October 29, 2001.
local: bupivacaine, levobupivacaine; surgery, orthopedic: hallux valgus repair.

Journal of Clinical Anesthesia 14:111114, 2002


2002 Elsevier Science Inc. All rights reserved. 0952-8180/02/$see front matter
655 Avenue of the Americas, New York, NY 10010 PII S0952-8180(01)00364-6
Original Contributions

Introduction proper muscular contraction a current of 0.3 to 0.4 mA.


Then, after careful aspiration, 1 mL of the study solution
Levobupivacaine is the most recent local anesthetic intro-
was slowly injected. If the muscular twitch disappeared
duced in clinical practice. Levobupivacaine is the S()-
after this test dose (Raj sign) another 9 mL of the study
enantiomer of the local anesthetic, bupivacaine. Whereas
solution was injected, with repeated aspiration tests. The
both the R and S enantiomers of bupivacaine have
sciatic nerve block was performed using a multiple stimu-
anesthetic activity, preclinical studies have suggested that
lation technique.79 After eliciting an appropriate stimu-
levobupivacaine may be less cardiotoxic than the racemic
lation of the tibial (plantar flexion/inversion of the foot)
mixture.1,2 Levobupivacaine is safe and effective for epi-
and the common peroneal nerve (dorsiflexion/eversion
dural and spinal anesthesia,2 4 as well as for supraclavic-
of the foot), 10 mL of the study solutions was injected for
ular brachial plexus blockade.5 Nonetheless, it is well
a total final volume of 20 mL.
established that the efficacy and clinical profile of local
An independent observer, who was blinded as to the
anesthetics that are used for peripheral nerve blocks also
type of local anesthetic solution injected, recorded the
depend on the type of block for which the drug is being
onset time of the sciatic nerve block. The zero time for
used.6 Thus the data obtained with the use of levobupiva-
clinical assessments was the completion of all anesthetic
caine for supraclavicular brachial plexus blockade may not
injections at the sciatic nerve. Surgical anesthesia was
be applied to lower extremity blocks, especially the sciatic
defined as complete loss of pinprick sensation (22-gauge)
nerve block.
in both sciatic branches, with inability to move the ankle
We therefore conducted a randomized, double-blind
and toes of the foot. The need for fentanyl supplementa-
study to compare the intraoperative and postoperative
tion (0.1 mg IV) or propofol sedation (3 to 4 mg/kg/hr
clinical properties of the sciatic nerve block performed
IV) so as to complete surgery was also recorded.
with either bupivacaine or levobupivacaine for orthopedic
After surgery, patients were given clear instructions on
foot procedures.
asking for analgesics as soon as they experienced pain at
the surgical site. The postoperative analgesia protocol
consisted of 100 mg IV ketoprofen every 8 hours associ-
Materials and Methods
ated with 100 mg IV tramadol on an as needed basis. The
After the study protocol had been approved by the Hos- time from the end of the local anesthetic injection to the
pital Ethical Committee, informed consent to participate recovery of sensory (recovery of pinprick sensation) and
in the study was obtained from 30 ASA physical status I and motor (ability in moving the ankle) functions on the
II patients undergoing elective hallux valgus repair with operated foot was also recorded, as well as the time for the
sciatic-femoral nerve block. Patients receiving chronic first postoperative pain medication.
analgesic therapy, and those patients with diabetes or Acceptance of the anesthetic technique was assessed 24
peripheral neuropathies, were excluded from the study. hours postoperatively using a two-point score: 1 Good, if
After an 18-gauge intravenous (IV) cannula was in- necessary I will repeat it; 2 Bad, I will never repeat it
serted in the forearm, midazolam 0.05 mg/kg IV was given again.7,8 At discharge from the orthopedic ward and 1
as premedication. Standard monitoring was used through- week after hospital discharge (at first routine postopera-
out the study, including non invasive arterial blood pres- tive orthopedic examination), patients were evaluated
sure (BP), heart rate (HR), and pulse oximetry. Surgery regarding the presence of persistent dysesthesia or deficit
was performed in all patients using a standard thigh of motor function on the operated limb.
tourniquet inflated 100 mmHg higher than systolic arte- Statistical analysis was performed using the program
rial blood pressure (SBP). For this reason, all patients also Systat 7.0 (SPSS Inc, Chicago, IL). The study sample size
received a femoral nerve block with 2% mepivacaine. was calculated to detect a 10 minute difference in the
Patients were randomly allocated via a computer-gen- onset of surgical block with an 80% power6 based on
erated randomization sequence to receive the sciatic nerve previous experiences.7 The Mann-Whitney U test was used
block with 20 mL of either 0.5% bupivacaine (Group to compare continuous variables, whereas categorical data
Bupivacaine, n 15), or 0.5% levobupivacaine (Group were analyzed using the contingency table analysis and
Levobupivacaine, n 15). Sterile syringes with the local Fishers exact test. A p-value 0.05 was considered to be
anesthetic solution were prepared by one of the authors statistically significant.
who was not involved in further management of the study
patients. Nerve blocks were performed using a nerve
Results
stimulator (Plexival, Medival, Italy) and a Teflon-coated
stimulating needle (Locoplex, Vygon, France) (needle No differences in age, weight, height, ASA physical status,
length/diameter were 3.5 cm/25-gauge for femoral nerve or ratio of males to females between groups were reported
block and 12 cm/22-gauge for sciatic nerve block). Pares- (Table 1).
thesia was never intentionally sought. The insulated nee- Figure 1 shows the onset time of the sciatic nerve block
dle was inserted according to the classic Labat approach for the two groups. Failed nerve block due to pain at the
modified by Winnie and connected to a nerve stimulator surgical site that required propofol sedation was reported
set up at 1 mA, 2 Hz, and 0.1 ms. After eliciting the proper in two patients, one patient from each group (6%) (p
muscular twitch, the stimulating current was progressively NS); where two patients in Group Bupivacaine (13.3%)
reduced and the needle position adjusted maintaining the and three patients in Group Levobupivacaine (20%) re-

112 J. Clin. Anesth., vol. 14, March 2002


Levobupivacaine vs. bupivacaine for sciatic nerve block: Casati et al.

Table 1. Demographic Variables of the Study Patients

Bupivacaine Levobupivacaine
(n 15) (n 15) p-value

Age (yrs) 56 (1869) 50 (1868) 0.17


Weight (kg) 67 (5289) 60 (4687) 0.64
Height (cm) 163 (157174) 165 (152175) 0.39
ASA physical status (I/II) 13/2 13/2 0.99
Gender (Male/Female) 3/12 3/12 0.99

Note: Results are presented as medians (ranges), with the exception of ASA physical status and gender distribution (numbers).

quired fentanyl supplementation to complete surgery be- plexus block, Cox et al.4 reported a mean onset time of 6
cause of tourniquet pain at the level of the thigh (p NS). to 8 minutes in all groups. However, the mean duration of
No differences in the times for recovery of sensory and sensory analgesia tended to be longer for levobupivacaine
motor blocks after surgery, as well as the time for first 0.5% (1,039 317 min) than levobupivacaine 0.25%
request of pain medication, were observed between the (892 250 min) or bupivacaine 0.5% (896 284 min),
two groups (Figure 2); and no differences in the number of even though this difference did not reach significance due
patients requiring rescue tramadol administration was to the between-patient variability. In the present investiga-
noted between the two groups [two patients in Group tion, the onset time observed with the sciatic nerve block
Bupivacaine (13%) and four patients in group Levobupi- was much longer than that reported by Cox et al.4 A
vacaine (26%)]. possible explanation for this observation is reasonably
Patient satisfaction with the anesthetic technique was related to the different type of nerve block, because the
similarly good in both groups (86% of patients in each large size of the sciatic nerve may render the onset of
group would accept the same anesthesia technique in the block less predictable than for other peripheral nerve.10 In
future). At the postoperative follow-up, no patient re- fact, Coventry and Todd,11 in evaluating the use of bupiv-
ported persistent dysesthesia or motor function deficits at acaine for sciatic nerve block, reported onset times of
the postoperative follow-up. approximately 30 minutes, and similar results have been
shown in other previous clinical studies.7,8,12
Similar to Cox et al.s results,4 in the present investiga-
Discussion
tion we also reported a 20% longer duration of postoper-
Our study provides original data related to the clinical use ative analgesia with 0.5% levobupivacaine than 0.5% bu-
of levobupivacaine for lower extremity blocks. This ran- pivacaine. This difference did not reach statistical
domized, double-blind study demonstrates that 20 mL of significance, but we cannot exclude a type two error when
0.5% levobupivacaine induces sciatic nerve block of simi- evaluating the duration of postoperative analgesia because
lar onset, duration, and intensity as the block produced of the relatively small sample size. Although no differences
with the same volume and concentration of the racemic in anesthetic potency have been reported between
solution of bupivacaine. levobupivacaine and racemic bupivacaine,13,14 levobupiva-
When comparing 0.4 mL/kg of two concentrations of
levobupivacaine (0.25% and 0.5%) with the same volume
of racemic bupivacaine 0.5% for supraclavicular brachial

Figure 2. Duration of motor and sensory blocks on the sciatic


nerve distribution and first request for postoperative pain
Figure 1. Onset times of sciatic nerve block in patients medication (Duration of analgesia) after sciatic nerve block
receiving either 0.5% bupivacaine (Group Bupivacaine, n performed with either 0.5% bupivacaine (Group Bupiva-
15) or 0.5% levobupivacaine (Group Levobupivacaine, n caine, n 15) or 0.5% levobupivacaine (Group Levobupiva-
15). Data are means SEM. caine, n 15). Data are means SEM.

J. Clin. Anesth., vol. 14, March 2002 113


Original Contributions

caine has been shown to have a greater vasoconstrictor S()-bupivacaine for elective lower limb surgery. Reg Anesth Pain
effect than racemic bupivacaine,15,16 and this could theo- Med 1999;24:519 23.
retically account for a trend toward a longer duration of 4. Cox CR, Checketts MR, MacKenzie N, Scott NB, Bannister J:
Comparison of S()-bupivacaine with racemic (RS)-bupivacaine
nerve blockade. However, when comparing the analgesic
in supraclavicular brachial plexus block. Br J Anaesth 1998;80:
efficacy of 50 mL of levobupivacaine 0.25% and bupiva- 594 8.
caine 0.25% for infiltration anesthesia in patients under- 5. Wedel DJ, Brown DL: Nerve blocks. In: Miller RD (ed): Anesthesia,
going inguinal herniorraphy, Bay-Nielsen and coworkers17 3rd ed. New York: Churchill-Livingstone, 1990:140737.
reported no differences in postoperative pain scores at 6. Browner WS, Black D, Newman B, Hulley SB: Estimating sample
rest and during ambulation, or in the consumption of size and power. In: Hulley SB, Cummings SR (eds): Designing
postoperative analgesics between the two drugs. Clinical ResearchAn Epidemiologic Approach. Baltimore: Williams
Hallux valgus repair is often associated with relevant & Wilkins, 1988:139 50.
postoperative pain that can be difficult to control with oral 7. Fanelli G, Casati A, Beccaria P, et al: A double-blind comparison
analgesics, although the use of long-acting local anesthet- of ropivacaine, bupivacaine, and mepivacaine during sciatic and
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acting local anesthetic available on the market but it also 1999;90:104753.
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ported because of the systemic absorption or inadvertent 10. Chelly JE, Delaunay L: A new anterior approach to the sciatic
intravascular injection.19,20 In animal studies, levobupiva- nerve block. Anesthesiology 1999;91:1655 60.
caine has been associated with a reduced depressant effect 11. Coventry DM, Todd JG: Alkalinsation of bupivacaine for sciatic
on the cardiovascular function than both dex- and racemic nerve blockade. Anesthesia 1989;44:46770.
12. Raj PP, Parks RI, Watson TD, Jenkins MT: A new single-position
bupivacaine,21,22 whereas in healthy volunteers levobupi-
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output than bupivacaine.23 Although our data suggest that 13. Aberg G: Toxicological and local anesthetic effects of optically
levobupivacaine is safe, properly powered studies with a active isomers of two local anesthetic compounds. Acta Pharmacol
much larger sample size are required to confirm these et Toxicol 1972;31:273 86.
preliminary findings. This is especially important for lower 14. Lyons G, Columb M, Wilson RC, Johnson RV: Epidural pain relief
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20. Heath ML: Deaths after intravenous regional anesthesia. Br Med J
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