Clonidine prolongs the action of local anesthetics in peripheral nerve blocks. This effect of clonidine could be mediated directly at the peripheral nerve because the drug inhibits impulse conduction in primary afferents and especially in C fibers (1,2). Used as the sole analgesic, clonidine produces analgesia after central neural block (3,4) and intraarticular injection administration (5). Only one clinical study has evaluated the analgesic effect of clonidine after plexus block when given as the sole analgesic (6). This prospective study evaluates the analgesic efficacy of interscalene clonidine after shoulder arthroscopy under general anesthesia.
After informed consent and institutional approval, 40 ASA physical status I and II patients scheduled for shoulder arthroscopy (decompression and rotator cuff repair) were prospectively included in this double-blinded study. Patients with the following conditions were excluded from this study: chronic use of clonidine, history of allergic reaction to any of the study drugs, peripheral neuropathies, and contraindications to brachial plexus block.
Patients did not receive any premedication. Arterial blood pressure, heart rate, and hemoglobin oxygen saturation were recorded during the entire study. Using a nerve stimulator, an interscalene catheter (Contiplex D, Braun, Sheffield, UK) was inserted by a single anesthesiologist experienced in the technique using a standard insertion procedure; the required position of the needle was determined when an output lower than 0.7 mA still produced a characteristic deltoid motor response. The catheter was advanced and secured with a transparent occlusive dressing. Paresthesias were not intentionally sought.
The patients were randomly divided into two groups. The interscalene group (n = 20) received clonidine 150 μg in 15 mL of saline through the catheter and 1 mL of subcutaneous saline. The systemic group (n = 20) received 15 mL of saline through the catheter and clonidine 150 μg (1 mL) subcutaneously. General anesthesia was induced with IV propofol 3 mg/kg and remifentanil and maintained with isoflurane and remifentanil with 50% N2O in O2 through an endotracheal tube.
On completion of arthroscopy, the patient was transferred to the postanesthesia care unit (PACU). Pain was evaluated for 24 h using a visual analog scale (VAS) by a nurse blinded to the analgesic technique used. The VAS, ranging from 0 mm (no pain) to 100 mm (worst imaginable pain), was assessed in the recovery room and 4, 8, 12, 16, and 24 h after surgery. Sensory block was evaluated using ice on the shoulder and scored as absent, diminished, or normal. Motor block was tested in the deltoid muscle and scored as absent, diminished, or normal.
All patients received patient-controlled analgesia via the interscalene catheter using 0.2% ropivacaine with an 8-mL bolus and a 1-h lockout interval. Additional postoperative analgesia was available with parenteral nalbuphine if required until VAS < 3. Analgesic duration was defined as the time from the end of surgery to the first requirement of an analgesic.
The postoperative analgesia protocol was initiated in the PACU and continued in the surgical ward. Data analysis was performed using SAS Software (version 8.2; SAS Institute Inc, Cary, NC). We defined analgesic duration as the primary outcome. Kaplan-Meier estimate was used to compare this outcome between the two groups. For this test, a P value <0.05 was considered to be statistically significant.
As a secondary analysis, we compared the groups according to ropivacaine and nalbuphine consumption and VAS scores measured at 0, 4, 8, 12, 16, and 24 h after surgery. For each of these variables, we found an equal variance between the two groups. VAS score at 0 h and ropivacaine and nalbuphine consumption had a normal distribution in both groups. A t-test was used to analyze these outcomes. VAS scores measured 4, 8, 12, 16, and 24 h after surgery did not have a normal distribution, thus we used Wilcoxon’s test for the statistical comparison of these variables in the two groups. For these secondary analyses, a P value <0.05 was considered to be statistically significant. Two-sided significance tests were used throughout.
No significant differences in age (47 ± 13 yr versus 53 ± 11 yr), sex (60% men in both groups), or weight (68 ± 11 kg versus 67 ± 8 kg) were reported between the two groups. The VAS pain scores were significantly lower in the interscalene group (mean, 16 mm; 95% confidence interval [CI], 9–23 mm) compared with the systemic group (mean, 58 mm; 95% CI, 53–63 mm) at 0 h (PACU stay;P < 0.0001). There were no significant between-group differences in VAS score at 4 h (P = 0.66), 8 h (P = 0.54), 12 h (P = 0.42), 16 h (P = 0.88), or 24 h (P = 0.77).
Ropivacaine consumption was significantly less in the interscalene group than in the systemic group (P < 0.0001). Similarly, a significant difference was observed between the groups for nalbuphine consumption 7 (95% CI, 3.6–10.4) versus 14 (95% CI, 8.7–19.3;P < 0.05).
Analgesic duration was significantly longer in the interscalene group (P < 0.00001) (Fig. 1). Sensory and motor function were preserved in all patients.
Three patients in the interscalene group and five in the systemic group had bradycardia in the PACU requiring treatment. One patient in the interscalene group and three in the systemic group had orthostatic hypotension after returning to the surgical ward requiring no therapeutic appeal.
The results of the present randomized, double-blinded study show that clonidine administered to the interscalene plexus without drugs produced analgesia compared with systemic administration. This suggests a direct peripheral action of clonidine. Moreover, the lack of motor or sensory block to light touch, which is what was tested, reflects the lack of block of A-β fibers. Such a finding would have interesting clinical applications, particularly in outpatient surgery where patients operated on with peripheral block anesthesia can leave the hospital setting while pain-free and after quick and complete recovery of sensory and motor function.
The postoperative pain scores were significantly lower in the interscalene group only during PACU stay. However, the analgesic duration was significantly longer in the interscalene group, suggesting that interscalene clonidine enhanced the postoperative analgesia compared with subcutaneous clonidine. Nevertheless, the adverse effects of clonidine limit the advantages of this method, particularly in outpatient surgery, because residual orthostatic hypotension places the patient at risk of falling after discharge. Moreover, the analgesic effect of interscalene clonidine alone was not sufficient in all patients in the interscalene group who required use of supplemental analgesia (ropivacaine and nalbuphine).
Concerning the mechanism of action of clonidine on peripheral nerves, Eisenach et al. (7), after a clinical review, concluded that a peripheral action of clonidine was evident. The duration of anesthesia or analgesia was enhanced by clonidine added to the local anesthetic after plexus block (8,9) but not by subcutaneous and IM clonidine injections (10,11). In in vitro experiments, Butterworth and Strichartz (1) and Gaumann et al. (2) showed direct neuronal effects of clonidine. In an isolated rabbit vagus preparation, a very small dose of clonidine enhances the effects of lidocaine on C-fiber action potentials. Other investigators proposed that clonidine may exert a peripheral analgesic action by releasing enkephalin-like substances (12).
When used as the sole analgesic, clonidine produces analgesia after central (3,4) block and intraarticular administration (5). In a previous study, we demonstrated that by selectively applying clonidine with local anesthetics in the midhumeral block technique, it is possible to prolong the duration of sensory block in one or several trunks of the brachial plexus (13). Sia et al. (6) used clonidine as the sole analgesic for axillary block. The authors concluded that the administration of clonidine alone through an axillary catheter did not enhance postoperative analgesia after hand and forearm surgery and that clonidine must be added to a local anesthetic to produce improvement in postoperative analgesia. However, the absence of efficacy in their study may be explained by the inability of clonidine administered through the axillary catheter to spread uniformly through the axillary sheath because of septa separating the nerves (14). Therefore, there may have been an insufficient concentration of the drug at the level of the nerve fibers. Moreover, the difference of efficacy with the present study may be explained by the proximity from the exit of these nerve roots from the spinal cord where clonidine produces postoperative analgesia.
In conclusion, clonidine administered to the interscalene plexus enhanced analgesia compared with systemic administration. There was an increased time to first analgesic request and a decreased need for postoperative analgesics. Nevertheless, the adverse effect of clonidine and its insufficiency in producing alone a profound depth of analgesia limits its use as routine management for postoperative analgesia.
1. Butterworth JF, Strichartz GR. The α2-adrenergic agonist clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers. Anesth Analg 1993; 76: 295–301.
2. Gaumann DM, Brunet PC, Jirounek P. Clonidine enhances the effects of lidocaine on C-fiber action potential. Anesth Analg 1992; 74: 719–25.
3. De Kock M, Wiederkher P, Langhmiche A. Epidural clonidine used as the sole analgesic agent during and after abdominal surgery: a dose-response study. Anesthesiology 1997; 86: 285–92.
4. Filos KS, Goudas LC, Patroni O, Polysou V. Intrathecal clonidine as the sole analgesic for pain relief after caesarean section. Anesthesiology 1992; 77: 267–74.
5. Gentili M, Juhel A, Bonnet F. Peripheral analgesic effect of intra-articular clonidine. Pain 1996; 64: 593–6.
6. Sia S, Lepri A. Clonidine administered as an axillary block does not affect postoperative pain when given as the sole analgesic. Anesth Analg 1999; 88: 1109–12.
7. Eisenach JC, De Kock M, Klimscha W. Alpha (2)-adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984–1995). Anesthesiology 1996; 85: 655–74.
8. Eledjam JJ, Deschodt L, Viel EJ. Brachial plexus block with bupivacaine: effects of added alpha adrenergic agents. Can J Anaesth 1991; 38: 870–5.
9. Berthelet Y, Capdevilla X. Continuous analgesia with a femoral catheter: plexus or femoral block? Ann Fr Anesth Reanim 1998; 17: 1199–205.
10. Gaumann D, Forster A, Griessen M, et al. Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. Anesth Analg 1992; 75: 69–74.
11. Molnar R, Davies MJ, Scott D, et al. Comparison of clonidine and epinephrine in lidocaine for cervical plexus block. Reg Anesth 1997; 22: 137–42.
12. Reuben SS, Steinberg RB, Klatt JL, Klatt ML. Intravenous regional anesthesia using lidocaine and clonidine. Anesthesiology 1999; 91: 654–8.
13. Iskandar H, Guillaume E, Dixmérias F. The enhancement of sensory blockade by clonidine selectively added to mepivacaine after midhumeral block. Anesth Analg 2001; 93: 771–5.
14. Thompson GE, Rorie DK. Functional anatomy of the brachial plexus sheaths. Anesthesiology 1983; 59: 117–59.