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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 bupivacaïne 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 and Stephan Kapral, MD

^* 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: 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{at}univie.ac.at

	Abstract

TOP Abstract Introduction Methods Results Discussion References

 
Purpose: To evaluate the effects of clonidine on three local anesthetics (mepivacaine 1%, ropivacaine 0.75% and bupivacaine 0.5%) with comparable potency and almost the same concentration-response relationship.

Methods: One hundred and twenty trauma-patients were randomly 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.

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 sensory 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 significantly prolonged (at 10 min: -45 ± 21; at 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 clonidine has a different impact on each of the three local anesthetics investigated in terms of onset and duration of block.

	Introduction

TOP Abstract Introduction Methods Results Discussion References

 
The three amino amid local anesthetics mepivacaine, bupivacaine and ropivacaine show differences in terms of onset, duration and quality of block, due to differences in their lipophilic side-chains. In the concentrations used, mepivacaine 1%, bupivacaine 0.5% and ropivacaine 0,75%, are almost equipotent with a very similar concentration-response relationship.^1,2 Clonidine,^3,4 an imidazole compound, has a history as a block prolonging adjuvant in regional anesthesia. The aim of the present study was to evaluate the effects of clonidine on these three substances on onset-time and duration of axillary perivascular brachial plexus block.

	Methods

TOP Abstract Introduction Methods Results Discussion References

 
After institutional approval and written informed consent, 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 perivascular approach according to Winnie was applied in all cases. To locate the plexus sheath, a nerve stimulator (Alphaplex^TM, 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.

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 difference of data the analysis of variance was performed. A P value <0.05 was considered significant.

	Results

TOP Abstract Introduction Methods Results Discussion References

 
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.

View larger version (29K): [in this window] [in a new window]   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.

	Discussion

TOP Abstract Introduction Methods Results Discussion References

Alpha 2-adrenoceptors are located on primary afferent 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 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 possible 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 vasodilatation 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 vasoconstricting 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 comparable duration of peripheral blockade. In the isolated rat vagus nerve, ropivacaine was less potent than bupivacaine in blocking A beta fibres, but it was more effective than bupivacaine in the blockade of A gamma and C-fibres. The two agents have almost identical dissociation constants with a pKa of 8.0 and 8.1 and similar apparent protein-binding capacity, but ropivacaine is less lipid soluble than bupivacaine. It would be reasonable to expect that a weaker binding to extra neural fat and tissues with ropivacaine might also contribute to greater availability of ropivacaine for transfer to the site of action in the nerves. These factors 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.

Clonidine is associated with specific side effects, specially cardiovascular (e.g., bradycardia, hypotension), and bupivacaine is known for its potential cardiotoxicity and cerebral convulsant activity. Ropivacaine appears well suited to achieve long lasting nerve blockade without having to resort to adjuvant medications.

Revision received February 12, 2001. Accepted for publication October 11, 2000.

	References

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3 Maze M, Tranquilli W. Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 1991; 74: 581–605.[Medline]

4 Eledjam JJ, Deschodt J, Viel EJ, et al. Brachial plexus block with bupivacaine: effects of added alpha- adrenergic agonists: comparison between clonidine and epinephrine. Can J Anaesth 1991; 38: 870–5.[Abstract]

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8 Ishiyama T, Dohi S, Iida H. The vascular effects of topical and intravenous ₂-adrenoceptor agonist clonidine on canine pial microcirculation. Anesth Analg 1998; 86: 766–72.[Abstract]

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10 Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992; 74: 719–25.[Abstract/Free Full Text]

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