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, MD*
o
lu, MD*
Departments of *Anaesthesiology and
Biostatistics, Trakya University Medical Faculty, Edirne, Turkey
Address correspondence and reprint requests to Dr. Dilek Memi, Trakya University Medical Faculty, Department of Anaesthesiology and Reanimation, 22030, Edirne, Turkey. Address e-mail to dilmemis{at}mynet.com
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Abstract |
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-2-adrenoceptors than clonidine. It decreases anesthetic requirements by up to 90% and induces analgesia in patients. We designed this study to evaluate the effect of dexmedetomidine when added to lidocaine in IV regional anesthesia (IVRA). We investigated onset and duration of sensory and motor blocks, the quality of the anesthesia, intraoperative-postoperative hemodynamic variables, and intraoperative-postoperative pain and sedation. Thirty patients undergoing hand surgery were randomly assigned to 2 groups to receive IVRA. They received 40 mL of 0.5% lidocaine and either 1 mL of isotonic saline (group L, n = 15) or 0.5 µg/kg dexmedetomidine (group LD, n = 15). Sensory and motor block onset and recovery times and anesthesia quality were noted. Before and after the tourniquet application at 5, 10, 15, 20, and 40 min, hemodynamic variables, tourniquet pain and sedation, and analgesic use were recorded. After the tourniquet deflation, at 30 min, and 2, 4, 6, 12, and 24 h, hemodynamic variables, pain and sedation values, time to first analgesic requirement, analgesic use, and side effects were noted. Shortened sensory and motor block onset times, prolonged sensory and motor block recovery times, prolonged tolerance for the tourniquet, and improved quality of anesthesia were found in group LD. Visual analog scale scores were significantly less in group LD in the intraoperative period and 30 min, and 2, 4, and 6 h after tourniquet release. Intra-postoperative analgesic requirements were significantly less in group LD. Time to first analgesic requirements was significantly longer in group LD in the postoperative period. We conclude that the addition of 0.5 µg/kg dexmedetomidine to lidocaine for IVRA improves quality of anesthesia and perioperative analgesia without causing side effects. IMPLICATIONS: This study was designed to evaluate the effect of dexmedetomidine when added to lidocaine for IV regional anesthesia. This is the first clinical study demonstrating that the addition of 0.5 µg/kg dexmedetomidine to lidocaine for IV regional anesthesia improves quality of anesthesia and intraoperative-postoperative analgesia without causing side effects.
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Introduction |
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IVRA has been limited by tourniquet pain and the inability to provide postoperative analgesia (3). One of the problems with IVRA, as compared with peripheral nerve blocks, is that there is no prolonged analgesic effect after tourniquet release. To improve the quality of IVRA block, the addition of various opioids to local anesthetics has been investigated with controversial results. A meta-analysis concluded that opioids lack significant effect (4).
-2-Adrenergic receptor (adrenoceptor) agonists have been the focus of interest for their sedative, analgesic, and perioperative sympatholytic and cardiovascular stabilizing effects with reduced anesthetic requirements. Dexmedetomidine, a potent -2-adrenoceptor agonist, is approximately 8 times more selective toward the -2-adrenoceptors than clonidine. Dexmedetomidine has been shown to decrease anesthetic requirements by up to 90% and to induce analgesia in rats, volunteers, and patients (5–9).
We designed this study to evaluate the effect of dexmedetomidine when added to lidocaine in IVRA. We planned to investigate the sensory and motor block onset and recovery time, the quality of anesthesia, intraoperative and postoperative hemodynamic variables, intraoperative and postoperative pain, sedation, and the other side effects of dexmedetomidine.
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Methods |
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Before establishing the anesthetic block, two cannulae were placed; one was in a vein on the dorsum of the operative hand and the other in the opposite hand for crystalloid infusion. The operative arm was elevated for 3 min then exsanguinated with an Esmarch bandage, and a pneumatic tourniquet (Tourniquet 2800 ELC, UMB; Medizintecknik, GmbH, Germany) was placed around the upper arm, and the proximal cuff was inflated to 250 mm Hg. Circulatory isolation of the arm was verified by inspection, absence of radial pulse, and loss of pulse oximetry tracing of the ipsilateral index finger. IVRA was achieved using 1 mL of saline plus 3 mg/kg lidocaine 0.5% (Aritmal; TEMS, Turkey) diluted with saline to a total dose of 40 mL in the lidocaine group (group L, n = 15) or 0.5 µg/kg dexmedetomidine (Precedex® 200 µg/2 mL; Abbott, North Chicago, IL) plus 3 mg/kg lidocaine 0.5% diluted with saline to a total dose of 40 mL in the dexmedetomidine group (group LD, n = 15). The solution was injected over 90 s by an anesthesiologist blinded to the injected drugs.
The sensory block was assessed by a pinprick performed with a 22-gauge short-beveled needle taken out continuously every 30 s. Patient response was evaluated in the dermatomal sensory distribution of the medial and lateral antebrachial cutaneous, ulnar, median, and radial nerves. Motor function was assessed by asking the subject to flex and extend his/her wrist and fingers, and complete motor block was noted when no voluntary movement was possible. Sensory block onset time was noted as the time elapsed from injection of study drug to sensory block achieved in all dermatomes, and motor block onset time was the time elapsed from injection of study drug to complete motor block.
After sensory and motor block was achieved, the distal cuff was inflated to 250 mm Hg followed by release of the proximal tourniquet and the operation was then started. MAP, HR, and SpO2 were monitored before and after tourniquet application, 5, 10, 15, 20, and 40 min after the injection of anesthetic by an anesthesiology resident, who knew which medication was administered. Hypotension (25% decrease from baseline value) was treated with IV ephedrine (3- to 9-mg bolus), bradycardia (25% decrease from baseline value) was treated with IV atropine 0.5 mg, and arterial oxygen saturation <91% was treated with O2 supplementation via a face mask.
Assessment of tourniquet pain scores was made on the basis of the visual analog scale (VAS) (0 = "no pain" and 10 = "worst pain imaginable") and degree of sedation (scale 1–5, 1 = completely awake, 2 = awake but drowsy, 3 = asleep but responsive to verbal commands, 4 = asleep but responsive to tactile stimulus, 5 = asleep and not responsive to any stimulus) (10) measured before and after tourniquet application, 5, 10, 15, 20, and 40 min after the injection of anesthetic. Intraoperatively, boluses of 1 µg/kg fentanyl were provided for tourniquet pain treatment when required (when VAS was >3), and total fentanyl (Fentanil Citrate; Abbott) consumption was recorded. Through the operation period if no tourniquet pain was encountered, the beginning of tourniquet pain was accepted as the duration of tourniquet application time.
After the operation, the surgeon, who did not know what medication was given, was asked to qualify the operative conditions according to the following numeric scale: 0 = unsuccessful, 1 = poor, 2 = acceptable, and 3 = perfect. All of the operations were performed by the same surgeon.
At the end of operation, the resident was asked to qualify the operative conditions according to following numeric scale: 4 (excellent) = no complaint from patient, 3 (good) = minor complaint with no need for supplemental analgesics, 2 (moderate) = complaint that required supplemental analgesics, and 1 (unsuccessful) = patient given general anesthesia.
The tourniquet was not deflated before 30 min and was not inflated for >1.5 h. At the end of surgery, the tourniquet deflation was performed by cyclic deflation technique. Sensory recovery time was noted (time elapsed after tourniquet deflation up to recovery of pain in all dermatomes determined by pinprick test). Motor block recovery time was noted.
Assessment of pain scores was made on the basis of the VAS. MAP, HR, VAS, and degree of sedation level values were recorded 30 min after tourniquet application, at hours 2, 4, 6, 12, and 24. Patients were instructed to receive 75 mg IM diclofenac once a day (Voltaren; Ciba-Geigy, Istanbul, Turkey) when VAS was >3, and total amounts of diclofenac administered to each group were recorded. The duration of analgesia was the time that elapsed between tourniquet release and the first IM intake of diclofenac. If no diclofenac was necessary within 24 h, the duration of analgesia was counted as 1440 min.
During the study period, any local or systemic complications were recorded. These measurements were recorded by an anesthesiology resident who did not know which medication was administered. Measurements in all patients were performed by the same person.
The statistical evaluation was done by the MINITAB program (no. WCP1331.00197; Minitab Inc., State College, PA). We considered that a clinically significant benefit of using dexmedetomidine would be a reduction in the tourniquet pain score (VAS) of 15% compared with the lidocaine control group. Based on these estimates, we calculated a sample size that would permit a type I error of = 0.05 and power of 80%. Enrollment of 15 patients in each group was required. Independent samples t-test was used for the evaluation of the demographic data, intraoperative-postoperative hemodynamic data, the time of the onset and the recovery of the sensorial block, and motor block, the duration of the operation and tourniquet, the onset time of tourniquet pain, duration of analgesia time, and intraoperative-postoperative analgesic use. Mann-Whitney U-test was used for intraoperative and postoperative VAS and sedation scores, and the quality of the anesthesia. Levels of significance were determined at P > 0.05 for no statistically significant difference, P < 0.05 for significant difference.
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Results |
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There was a statistical difference between groups when compared for VAS scores for tourniquet pain after tourniquet inflation at 5, 10, 15, 20, and 40 min; there was a statistically highly significant lower VAS in group LD (P < 0.001) (Fig. 1). The initial time of tourniquet pain was significantly longer in group LD (P < 0.001). The difference in the total dose of fentanyl was statistically significantly less in group LD when compared with group L (P < 0.001) (Table 1). The addition of dexmedetomidine for lidocaine IVRA delayed the onset of unbearable tourniquet pain and decreased analgesic consumption (fentanyl) for tourniquet pain relief when compared with the lidocaine group (P < 0.001). Fourteen patients in group L received additional analgesic in the intraoperative period, whereas 10 patients were given fentanyl in group LD, and this was statistically insignificant (P > 0.05).
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Discussion |
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Gentili et al. (10) were the first to report the efficacy of IVRA clonidine in decreasing tourniquet pain. Reuben and Sklar (11) evaluated the safety and efficacy of administering IVRA with 1 µg/kg clonidine in the management of complex regional pain syndrome of the knee and found that clonidine was a useful treatment modality for its management without significant side effects. Gorgias et al. (12) compared the efficacy of a 1 µg/kg clonidine added to IVRA with lidocaine to prevent tourniquet pain and found that the addition of 1 µg/kg clonidine to lidocaine for IVRA delayed the onset of unbearable tourniquet pain and decreased analgesic consumption for tourniquet pain relief. Lurie et al. (13) evaluated the efficacy of 1 µg/kg clonidine added to IVRA-lidocaine in decreasing the onset of severe tourniquet pain and found that it delayed the onset time. During our literature search, we did not find any study of dexmedetomidine added to lidocaine for IVRA. Dexmedetomidine is approximately 8 times more selective toward the -2-adrenoceptors than clonidine (5). Therefore, we assumed that dexmedetomidine may be effective in IVRA. A limitation of our study was the failure to assess dexmedetomidine’s systemic effect through IM administration. Further research is needed to clarify this issue.
-2-Adrenergic agonists produce sedation, and electroencephalographic studies confirm the increase in stage I and II sleep. The hypnotic response probably is mediated by activation of -2-adrenoceptors in the locus coeruleus, which are coupled via a pertussis toxin-sensitive G protein to a change in conductance through an ion channel (14). Inhibition of adenylate cyclase also may be involved in the hypnotic response. Centrally active -adrenergic agonists exert powerful analgesic action that probably is transduced at several levels, only one of which has been definitively confirmed. At the level of the dorsal root neuron, -2 agonists inhibit substance P release in the nociceptive pathway. Concerning the molecular components involved in the analgesic response, there seems to be a clear-cut dependence on a pertussis toxin-sensitive G protein for the analgesic response to an -2-adrenergic agonist (5). In addition, -2-adrenergic receptors located at nerve endings may have a role in the analgesic effect of the drug by preventing norepinephrine release (15).
Although there is strong evidence that stimulation of -2-receptors leads to production of analgesia at the spinal cord level (8), the analgesic effects of dexmedetomidine in the clinical setting have been investigated primarily in regard to its opioid-sparing action. Perioperative dexmedetomidine administration decreased the requirements for opioid or non-opioid analgesics both intra- and postoperatively (16). In a study in women undergoing laparoscopic tubal ligation, morphine was required in 33% of patients administered (0.4 µg/kg IV) postoperative analgesia, compared with 83% of patients administered diclofenac (6). Jaakola et al. (17) demonstrated the analgesic efficacy of dexmedetomidine in human tourniquet pain. In their study, a single IV dose of fentanyl and dexmedetomidine (0.25, 0.5, and 1 µ/kg) was administered. They found that dexmedetomidine clearly demonstrated an analgesic effect in the tourniquet test, but the subjective VAS ratings tended to be lower after fentanyl than after dexmedetomidine and the analgesic action of dexmedetomidine was not clearly dose-dependent; an apparent ceiling effect was seen at the 0.5 µ/kg dose of dexmedetomidine. We also used 0.5 µ/kg dexmedetomidine in our study.
Jaakola (18) assessed the efficacy and safety of IV dexmedetomidine as a premedication before IVRA. She found that 1 µ/kg dexmedetomidine was an effective premedication before IVRA because it reduced patient anxiety, sympathoadrenal responses, and opioid analgesic requirements but it did not reduce tourniquet pain. Tourniquet pain and total fentanyl consumption were reduced by the dexmedetomidine-containing lidocaine solution in our study. Tourniquet pain is a common problem complicating the use of a pneumatic tourniquet during surgical procedures involving the upper or lower limb. The mechanism of tourniquet pain remains unclear despite the role of A fibers and unmyelinated C fibers (19). Clonidine has also been reported to depress nerve action potentials, especially in C fibers, by a mechanism independent of the stimulation of -2-adrenergic receptors (20). This mechanism accounts for strengthening of the local anesthetic block achieved by perineural administration of the drug and could be implicated in the effect seen in our study. Finally, -2-adrenergic receptors located at nerve endings may have a role in the analgesic effect of the drug by preventing norepinephrine release (15). In our study, we considered that dexmedetomidine, in addition to its local anesthetic effect, delayed the onset of tourniquet pain and reduced intra- and postoperative analgesic requirement.
Acute dexmedetomidine IV administration produces abrupt hypertension and bradycardia until the central sympatholytic effect dominates, resulting in moderate decreases in both MAP and HR from baseline, and it also has a sedative effect (21). Its sedative, proanesthetic, and proanalgesic effects at 0.5–2 µg/kg given IV stem mainly from its ability to blunt the central sympathetic response. It also minimizes opioid-induced muscle rigidity, lessens postoperative shivering, causes minimal respiratory depression, and has hemodynamic stabilizing effects (22). In our study, small-dose use of dexmedetomidine and atropine that was given as premedication might presumably have resulted in a lesser degree of such side effects.
This is the first clinical study demonstrating that the addition of 0.5 µg/kg dexmedetomidine to lidocaine for IVRA, improves quality of anesthesia and improves intraoperative-postoperative analgesia without causing side effects.
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References |
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2-adrenergic agonist. Pharmacol Toxicol 1991; 68: 140–3.[ISI][Medline]
2-adrenergic agonists. Ann NY Acad Sci 1991; 625: 409–22.[ISI][Medline]
2-adrenoceptor agonist—in healthy volunteers. Pain 1991; 46: 281–5.[ISI][Medline]
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