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REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Tramadol Added to Mepivacaine Prolongs the Duration of an Axillary Brachial Plexus Blockade

Stephan Kapral, MD^*, Gabriele Gollmann, MD, Barbara Waltl, MD^*, Rudolf Likar, MD, Robert N. Sladen, MD^§, Christian Weinstabl, MD^*, and Franz Lehofer, MD

*Department of Anesthesia and General Intensive Care, University of Vienna, Vienna; Department of Anesthesia, DOKH Friesach; Department of Anesthesia and General Intensive Care, LKH Klagenfurt, Klagenfurt, Austria; and §Department of Anesthesiology, Columbia-Presbyterian Medical Center, New York, New York

Address correspondence and reprint requests to Stephan Kapral, MD, Department of Anesthesia and General Intensive Care, University of Vienna, 18-20, Waehringer Guertel, A-1090 Vienna, Austria. Address e-mail to Stephan.Kapral{at}univie.ac.at

	Abstract

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Tramadol is an analgesic drug that is antagonized by ₂-adrenoceptor antagonists, as well as opioid antagonists. We hypothesized that tramadol might produce effects on an axillary brachial plexus blockade similar to those of clonidine. We designed a prospective, controlled, double-blinded study to assess the impact of tramadol added to mepivacaine on the duration of an axillary brachial plexus blockade. After institutional approval and informed consent, 60 patients (ASA physical status I or II) scheduled for forearm and hand surgery after trauma under brachial plexus anesthesia were included in the study. Patients were randomly assigned to receive either 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution (Group A, n = 20); 40 mL of mepivacaine 1% with 100 mg of tramadol (Group B, n = 20); or 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution and 100 mg of tramadol IV (Group C, n = 20). Sensory block, motor block, and hemodynamics were recorded before and 5, 10, 30, 60, 120, 180, and 360 min after local anesthetic injection. Duration of sensory and motor block was significantly longer (P < 0.01; P < 0.05) in Group B (299 ± 84 and 259 ± 76 min) than in Group A (194 ± 35 and 181 ± 24 min) and Group C (187 ± 35 and 179 ± 16 min). There was no difference in onset of sensory and motor blockade among groups. Hemodynamics remained unchanged in all patients throughout the study period. We conclude that the addition of tramadol prolongs the duration of brachial plexus block without side effects. Tramadol may be an alternative to epinephrine or clonidine as an adjuvant to local anesthesia for an axillary block.

Implications: This study demonstrates that the admixture of 100 mg of tramadol with mepivacaine 1% for brachial plexus block provides a pronounced prolongation of blockade without side effects. Our data support a specific analgesic effect of tramadol on peripheral nerves.

	Introduction

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During the last few years, clonidine has been studied as an adjunct to general and regional anesthesia. Clonidine increases the duration of anesthesia and analgesia when mixed with local anesthetics used for brachial plexus blockade (1,2). However, the central analgesic, tramadol, is successful in the management of pain. It is formulated as a racemic mixture with each enantiomer displaying different opioid-receptor binding properties, monoaminergic reuptake inhibition, and metabolic pathways (3,4). Like codeine, tramadol has a methyl group substitution on the phenolic moiety, which explains its weak affinity for opioid receptors (5). Tramadol was initially reported to lack selectivity for µ-, -, or -receptors (5), but in a more recent study, it has been demonstrated to be selective for the µ-receptor (4). Furthermore, the M1 metabolite of tramadol, which is produced by O-demethylation (6), shows higher affinity for opioid receptors than the parent drug (5). Tramadol also inhibits norepinephrine and serotonin reuptake in rat brain synaptosomes (7). Moreover, pretreatment with yohimbine and idazoxan (both ₂-adrenoceptor antagonists) can significantly reduce the antinociceptive effect of IV tramadol (5). Based on this profile of action, we hypothesized that the effect of adding tramadol to local anesthetics for brachial plexus blockade would be comparable to that of clonidine and result in an increased duration of blockade.

Thus, the aim of this placebo-controlled investigation was to evaluate the effect of tramadol added to mepivacaine for an axillary brachial plexus block on the quality, onset, and duration of blockade.

	Methods

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After institutional approval and informed consent, 60 ASA physical status I or II patients scheduled for forearm and hand surgery after trauma during an axillary blockade were included in the study. Patients receiving adrenoceptor agonist or antagonist therapy; those with a history of cardiac, respiratory, hepatic and/or renal failure; and pregnant women were excluded from the study. Axillary blockade was performed with the patient in the supine position with the upper arm abducted 90° and the elbow flexed at 110°. After preparation of the area, the axillary artery was palpated in the proximal part of the axilla and a skin wheal was injected using 2 mL of lidocaine 1%. A nerve stimulator was used for precise localization of a 24-gauge, 7-cm Sprotte needle. The position of the needle was judged adequate when an output current <0.5 mA still elicited a slight distal motor response. During local anesthetic injection, firm digital pressure was applied immediately distal to the puncture site.

Patients were randomly assigned to receive either 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution (Group A, n = 20); 40 mL of mepivacaine 1% with 100 mg of tramadol (Group B, n = 20); or 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution and 100 mg of tramadol IV (Group C, n = 20) in a double-blinded fashion. All local anesthetic solutions and adjuvant drugs were prepared by an anesthesiologist not involved in the performance of brachial plexus block, patient care, and data collection. Sensory blockade and motor blockade of musculocutaneous, radial, median, and ulnar nerves were recorded after 5, 10, 30, 60, 120, 180, and 360 min. Sensory blockade of each nerve was assessed by pinprick and compared with the same stimulation on the contralateral arm. Sensory blockade was rated on a scale from 100% (normal sensation) to 0% (no sensation). 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 using a modification of the Lovett rating scale (Table 1) (8,9). Duration of sensory block was considered as the time interval between the local anesthetic administration and the offset of paresthesia, and the duration of motor block was defined as the time interval between the local anesthetic administration and the recovery of motor block.

The size of the groups was estimated based on a pilot study using Machin and Campbell tables. Data are expressed as mean ± SD. For statistical analysis and comparison among the groups, Levene’s test for equality of variances and Bonferroni-corrected Student’s t-test, for unpaired samples, were used. A P value <0.05 was considered significant.

	Results

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The main finding of our study was that the duration of sensory and motor block in Group B (299 ± 84 and 259 ± 76 min) was significantly longer than that in Group A (194 ± 35 and 181 ± 24 min) and Group C (187 ± 35 and 179 ± 16 min) using Levene’s test (P < 0.01 and P < 0.05), as well as Student’s t-test (P < 0.01 and P < 0.05) with Bonferroni correction. The duration of sensory and motor block was not statistically different between Groups A and C. There was no difference in the duration of onset time among the three groups. As shown in Table 2, sensory and motor scores indicate increased blockade in Group B compared with Groups A and C at the 120 and 180 min time points. As summarized in Table 3, the three groups were not different with regard to age, body weight, height, duration of operation, and tourniquet application. All patients in all groups underwent forearm and hand surgery after trauma and surgical anesthesia was achieved in 19 of 20 patients in Groups A and B and in 18 of 20 patients in Group C. The onset of motor and sensory block of each nerve distribution is presented in Table 2; there was no statistical difference among the groups. No difference in the quality of blockade was recorded among the groups. Intraoperative pain due to tourniquet application during surgery was noted in three patients in Group A and in four patients each in Groups B and C. In these patients, pain resolved immediately after release of the tourniquet without any additional analgesic requirement. Heart rate, systolic and diastolic arterial pressure, oxygen saturation, respiratory rate, and sedation score remained stable; no differences were noted among groups. A slight decrease in sedation score was obtained during the first 30 min after blockade without differences among the study groups. No side effects, including nausea and vomiting, were reported in patients in Groups A and B, whereas in Group C, three patients had nausea and one of them vomited.

	Discussion

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As mentioned previously, tramadol influences the monoaminergic system, with pain-modulating effects. It inhibits norepinephrine and 5-hydroxy-tryptamine reuptake (6). Moreover, pretreatment with yohimbine and idazoxan—both ₂-adrenoceptor antagonists—results in a significant reduction of the antinociceptive effect of tramadol in rats (11). Similar results were obtained in healthy volunteers in whom IV tramadol was antagonized by naloxone and yohimbine (12). The epidural administration of tramadol results in good pain relief with a long duration and minimal side effects in the postoperative period after abdominal surgery (13). It has been demonstrated that epidural tramadol infusion resulted in a significantly lower serum concentration than the same amount administered IV (14). These findings suggest that tramadol can interact with receptors in the posterior horn of the spinal cord and that its mechanism of action may be comparable to that of clonidine.

The use of tramadol as an adjuvant to local anesthetics for peripheral nerve blocks has never been described before, and its mechanism of action, as well as its metabolism, are not clearly understood. To our knowledge, data confirming a specific analgesic effect of clonidine on peripheral nerves are still missing (1). Vasoconstriction, the presumed mechanism of action for epinephrine’s adjunctive effect on local anesthetics, is probably not responsible for block prolongation by clonidine (15). Singelyn et al. (2) demonstrated that clonidine mixed in local anesthetic solution for brachial plexus block had a significantly longer duration of block compared with IV clonidine during plexus block. These data are in accordance with Chiari et al.’s study (16), in which no difference of bupivacaine plasma level was measured during brachial plexus block with and without clonidine. Similarly, no vasoconstrictive effects have been observed in any of the studies dealing with tramadol. To explain this controversial finding, we must assume that the mechanism of action of clonidine and tramadol as adjuncts to local anesthetics for peripheral nerve block is a local effect on the nerve that is not mediated via receptors. This suggests that clonidine and/or tramadol might modify the action of local anesthetic at the sodium channel either directly or indirectly (17).

In conclusion, the admixture of 100 mg of tramadol with mepivacaine 1% for brachial plexus block provides a pronounced prolongation of blockade without any discernible difference in heart rate or blood pressure. Additionally, our data support a specific analgesic effect of tramadol on peripheral nerves. Consequently, the results of the present investigation suggest that tramadol may be a useful alternative to epinephrine and clonidine as an adjuvant to local anesthesia for brachial plexus block.

	Footnotes

 
Presented in part at the annual meeting of the ASRA, San Diego, CA, March 1996; and at the annual meeting of the ESA, London, UK, June 1996.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999