Full text of DOI:10.1007/BF03016825

522
General Anesthesia
Clonidine as adjuvant for mepivacaine, ropivacaine
and bupivacaine in axillary, perivascular brachial
plexus block
[La clonidine comme adjuvant à la mépivacaïne, la ropivacaïne et la bupiva-
caïne pour une anesthésie par bloc brachial axillaire périvasculaire]
Wolfgang Erlacher MD,* Christoph Schuschnig MD,* Herbert Koinig MD,† Peter Marhofer MD,†
Matthias Melischek MD,† Nikolaus Mayer MD,† Stephan Kapral MD†
Purpose: To evaluate the effects of clonidine on three local anes-
thetics (mepivacaine 1%, ropivacaine 0.75% and bupivacaine
0.5%) with comparable potency and almost the same concentra-
tion-response relationship.
investigated in terms of onset and duration of block.
Objectif : Évaluer les effets de la clonidine sur trois anesthésiques
locaux à puissance comparable (la mépivacaïne à 1 %, la ropivacaïne
à 0,75 % et la bupivacaïne à 0,5 %) qui présentent une relation con-
centration-réponse presque similaire.
Methods: One hundred and twenty trauma-patients were ran-
domly allocated into six groups. In the control-groups (Mo/Ro/Bo)
brachial plexus was performed using 40 mL of local anesthetic plus
1 mL of NaCL 0.9%. In the clonidine-groups (Mc/Rc/Bc) brachial
plexus was performed using each 40 mL of drug plus 1 mL (0.150
mg) of clonidine. Onset-time and the duration of the sensory block
were recorded. Data are expressed as mean ± SD.
Méthode : Cent vingt patients victimes de traumatisme ont été répar-
tis au hasard en six groupes. Dans les groupes témoins (Mo/Ro/Bo), le
bloc du plexus brachial comprenait 40 mL d’anesthésique local plus 1
mL de NaCL à 0,9 %. Dans les groupes clonidine (Mc/Rc/Bc), il com-
prenait 40 mL d’anesthésique local plus 1 mL (0,150 mg) de cloni-
dine. Le délai d’installation et la durée du blocage sensitif ont été notés
et exprimés comme la moyenne ± l’écart type.
Results: According to the average sensory block determined by a
visual analog scale in the median, ulnar and radial nerve distributions
and ranging from 100 (no sensory blockade) to 0 (complete senso-
ry blockade), both mepi-groups showed a rapid onset (at 10 min: -
Mo 20 ± 15 / Mc 19 ± 14; at 30 min: -Mo 3 ± 4 / Mc 5 ± 4).
The ropi-and bupi- groups both had a longer onset time (at 10 min:
-Ro 23 ± 19 / Rc 25 ± 22 / Bo 24 ± 15; at 30 min -Ro1 0 ± 6 /
Rc11 ± 6 / Bo 12 ± 4). The onset time in group-Bc was signifi-
cantly prolonged (at 10 min: -45 ± 21; at 30 min: -20 ± 6).
Résultats : D’après le bloc sensitif moyen, déterminé par une échelle
visuelle analogique appliquée aux distributions des nerfs médian, cubital
et radial et qui s’étend de 100 (aucune anesthésie) à 0 (blocage sen-
sitif complet), les deux groupes de mépivacaïne ont indiqué une instal-
lation rapide (à 10 min : -Mo 20 ± 15 / Mc 19 ± 14; à 30 min : -Mo
3 ± 4 / Mc 5 ± 4). Les groupes ropivacaïne et bupivacaïne ont présen-
té un plus long délai d’installation (à 10 min : -Ro 23 ± 19 / Rc 25 ±
22 / Bo 24 ± 15; à 30 min : -Ro 10 ± 6/ Rc11 ± 6 / Bo 12 ± 4).
Le délai d’installation s’est prolongé de façon significative dans le groupe
-Bc (à 10 min : -45 ± 21; à 30 min : -20 ± 6).
Duration of motor blockade was prolonged by clonidine only in the
mepivacaine and bupivacaine groups; (in minutes: Mo 212 ± 47 -Mc
468 ± 62; Ro 702 ± 52 -Rc 712 ± 82; Bo 728 ± 36 -Bc 972 ± 72).
Conclusion: The present study shows that the addition of cloni-
dine has a different impact on each of the three local anesthetics
From Department of Anaesthesia and Intensive Care,* Hospital Lainz and the Department of Anaesthesia and General Intensive Care,†
University of Vienna, Vienna, Austria.
Address correspondence to: Dr. Wolfgang Erlacher, Department of Anaesthesia and General Intensive Care, Krankenhaus Lainz,
Wolkersbergenstr. 1, A–1130 Vienna, Austria.
Phone: 0043-1-80110-2646; Fax: 0043-1-80110-2696; E-mail: Wolfgang.Erlacher@univie.ac.at
Accepted for publication October 11, 2000.
Revision accepted February 12, 2001.

Erlacher et al.: CLONIDINE AS ADJUVANT
523
La durée du blocage moteur a été prolongée par la clonidine dans les
groupes mépivacaïne et bupivacaïne seulement; (en minutes : Mo 212
± 47 -Mc 468 ± 62; Ro 702 ± 52 -Rc 712 ± 82; Bo 728 ± 36
-Bc 972 ± 72).
TABLE I Group-assignment
Group Mo 40 mL of mepivacaine 1% plus 1 mL of NaCL 0.9%
Group Mc 40 mL of mepivacaine plus 1 mL (0.150 mg) of
clonidine
Group Ro 40 mL of ropivacaine 0.75% plus 1 mL of NaCL 0.9%
Group Rc 40 mL of ropivacaine 0.75% plus 1 mL (0.150 mg) of
clonidine
Group Bo 40 mL of bupivacaine 0.5% plus 1 mL of NaCL 0.9%
Group Bc 40 mL of bupivacaine 0.5% plus 1 mL (0.150 mg) of
clonidine
Conclusion : La présente étude montre que l’addition de clonidine
provoque des effets différents sur chacun des trois anesthésiques
locaux expérimentés quant au délai d’installation et à la durée de
l’anesthésie.
TABLE II Clinical characteristics
The three amino amid local anesthetics
mepivacaine, bupivacaine and ropivacaine
show differences in terms of onset, duration
Group
Mo
Group Group
Mc Ro
Group
Rc
Group Group
Bo
Bc
T
and quality of block, due to differences in
Sex (m/f) 11/9
10/10 7/13
9/11
11/9
9/11
their lipophilic side-chains. In the concentrations used,
mepivacaine 1%, bupivacaine 0.5% and ropivacaine
0,75%, are almost equipotent with a very similar con-
centration-response relationship.1,2 Clonidine,3, 4 an
imidazole compound, has a history as a block prolong-
ing adjuvant in regional anesthesia. The aim of the pre-
sent study was to evaluate the effects of clonidine on
these three substances on onset-time and duration of
axillary perivascular brachial plexus block.
Age (yr)
Weight
(kg)
Height
(cm)
44 21 46 19 40 13 46 20 46 14 48 20
70 13 74 76 13 74 13 77 12 73
169 172 170 16 170 11 173 170 7
8
9
6
8
8
TABLE III Onset time of sensory blockade
5 min
10 min
20 min
30 min
Group Mo
Group Mc
Group Ro
Group Rc
Group Bo
Group Bc
35 22
38 24
68 24
64 26
68 26
63 25
20 15
19 14
23 19
25 22
24 15
10
12
16 10
17 10
7
6
4
5
10
11
12
3
4
6
6
4
Methods
After institutional approval and written informed con-
sent, we consecutively investigated 120 patients (ASA
I–III) undergoing surgery of the forearm or hand
after trauma, under axillary perivascular brachial
plexus block. A standard block technique for a perivas-
cular approach according to Winnie was applied in all
cases. To locate the plexus sheath, a nerve stimulator
(Alphaplex™, Sterimed, Germany) with a 24-gauge, 4
cm Sprotte needle was used. Patients were allocated in
six groups in a controlled, randomised double-blinded
design using a computer-generated randomisation list.
Table I shows how groups were assigned.
16
6
45 21* 26 9*
20 6*
*P <0.05
Table III shows the average sensory block by visual analog scale of
the median, radial and ulnar nerves for measurements after
5/10/20 and 30 min. The visual analog scale ranges from 100
(no sensory blockade) to 0 (complete sensory blockade) and was
determined selectively for each nerve distribution.
Injection time was chosen as the beginning of all
time intervals. Sensory block and motor block of mus-
culocutaneous, radial, ulnar and median nerve were
recorded after five, 15, 30, 60, 120, 180, 360 and 480
min. Sensory block was determined by a visual ana-
logue-scale in comparison to the contra lateral arm
from 100 (no sign of sensory blockade) to 0 (com-
plete sensory blockade). Sensory onset of each nerve
was assessed by pinprick and compared to the same
stimulation on the contra lateral arm. Motor block
was evaluated by thumb abduction (radial nerve),
thumb adduction (ulnar nerve), thumb opposition
(median nerve) and flexion of the elbow in supination
and pronation of the forearm (musculocutaneous
nerve). Measurements were performed by using a
modification of the Lovett rating scale, from 6 (nor-
mal muscular force) to 0 (complete paralysis).5 The
duration of sensory block was considered as the time
interval between the administration of the local anes-
thetic and the first postoperative pain. Heart rate,
non-invasive blood pressure, oxygen saturation, were
measured at the same time points.
The necessary sample size was estimated by data of
previous studies using Machin and Campbell tables.
Data were expressed as mean
SD. For statistical
analysis of demographic data and for comparison of
groups paired t test and for the comparison of differ-
ence of data the analysis of variance was performed. A
P value <0.05 was considered significant.

524
CANADIAN JOURNAL OF ANESTHESIA
reduced absorption from the injection site was an other
point of discussion, but compared with epinephrine as
adjuvant it failed to influence plasma levels, indicating a
direct action on the nerve.
The addition of clonidine to mepivacaine 1% and to
bupivacaine 0.5% resulted in a very impressive block
prolongation but did not lead to an additional block
prolonging effect in the ropivacaine group.6 A possi-
ble explanation for these negative findings may be the
conditions permitting a synergistic effect of clonidine
and the local anesthetic chosen. Studies have been
performed in volunteers to determine the effect of
ropivacaine compared with bupivacaine and lidocaine
on cutaneous blood flow after injection of 0.1 mL.
Both, bupivacaine and lidocaine produced vasodilata-
tion in human skin, but ropivacaine decreased skin
blood flow.7 In dogs, a significant constriction of the
pial arteries could be shown after the local application
of ropivacaine. 8 As ropivacaine had intrinsic vasocon-
stricting properties not mediated by an activation of
alpha 2-adrenoceptors, this could have explained why
the addition of clonidine did not result in any benefit.
Ropivacaine and bupivacaine resulted in compara-
ble duration of peripheral blockade. In the isolated rat
vagus nerve, ropivacaine was less potent than bupiva-
caine in blocking A beta fibres, but it was more effec-
tive than bupivacaine in the blockade of A gamma and
C-fibres. The two agents have almost identical disso-
ciation constants with a pKa of 8.0 and 8.1 and simi-
lar apparent protein-binding capacity, but ropivacaine
is less lipid soluble than bupivacaine. It would be rea-
sonable to expect that a weaker binding to extra neur-
al fat and tissues with ropivacaine might also
contribute to greater availability of ropivacaine for
transfer to the site of action in the nerves. These fac-
tors could have explained the tendency towards a
more rapid block onset obtained with ropivacaine.9,10
It might be speculated that stereospecific factors are
involved in the mechanism of action of clonidine on
the sodium-channels.
FIGURE Duration of motor blockade with mepivacaine 1%,
bupivacaine 0.5%, ropivacaine 0.75% with and without clonidine
0.150 mg. The duration of blockade (in minutes) is prolonged by
the addition of clonidine in the mepivacaine and the bupivacaine-
groups. Block was not prolonged by clonidine in the ropivacaine-
group.
Results
Clinical characteristics were not different between
groups (Table II). The addition of clonidine resulted
in a block-prolonging effect, both in the mepivacaine
1%-group, and in the bupivacaine 0.5%-group. As
adjuvant for ropivacaine 0.75%, clonidine failed to
prolong the block (Figure). Onset of sensory block
was significantly shorter in both mepivacaine-groups.
The bupivacaine-and ropivacaine-groups all had a
longer onset-time, in the bupivacaine/clonidine-
group the onset was even significantly prolonged
(Table III). Hemodynamic parameters (data not
shown) were stable in all groups throughout the entire
study period. Side effects, such as hypotension, nausea
and vomiting were not recorded in any of the cases.
Discussion
The major finding of the present study is that the
addition of clonidine has a different impact on each of
the three investigated local anesthetics in terms of
onset and block prolonging activity.
Clonidine is associated with specific side effects, spe-
cially cardiovascular (e.g., bradycardia, hypotension),
and bupivacaine is known for its potential cardiotoxici-
ty and cerebral convulsant activity. Ropivacaine appears
well suited to achieve long lasting nerve blockade with-
out having to resort to adjuvant medications.
Alpha 2-adrenoceptors are located on primary affer-
ent terminals, on neurons in the superficial laminae of
the spinal cord, and within several brainstem nuclei
implicated in analgesia, supporting the possibility of
analgetic action at peripheral, spinal, and brainstem
sites. Clonidine enhances both sensory and motor
blockade from epidural or peripheral nerve injection of
local anesthetics. Clonidine blocks conduction of C and
A gamma fibres and increases potassium conductance in
isolated neurons and intensifies conduction block of
local anesthetics. Local vasoconstriction resulting in
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