|Year : 2015 | Volume
| Issue : 4 | Page : 664-669
Addition of dexmedetomidine to a safe intravenous dose of lidocaine for intravenous regional anesthesia
Ashraf A Abdelkader MD, PhD 1, Ayman A Kasem1, Ayman Rayan2
1 Department of Anesthesia and Intensive Care, Ain Shams University, Cairo, Egypt
2 Department of Anesthesia and Intensive Care, Monofya University, Menoufia, Egypt
|Date of Submission||19-Jun-2014|
|Date of Acceptance||15-Oct-2014|
|Date of Web Publication||29-Dec-2015|
Ashraf A Abdelkader
Ain Shams University Hospitals, Cairo
Source of Support: None, Conflict of Interest: None
Intravenous regional anesthesia (IVRA) is a simple and reliable type of regional anesthesia. However, it has some limitations such as tourniquet pain, lack of postoperative analgesia, and local anesthetic toxicity in case of tourniquet malfunction. Various additives to local anesthetics, such as opioids, NSAID, ketamine, and clonidine, are used.
The aim of this study was to evaluate the addition of dexmedetomidine to a safe intravenous dose of lidocaine for IVRA.
Patients and methods
a total of 50 patients undergoing elective superficial hand surgery were assigned into two groups: the L group and the LD group. In the L group, IVRA was achieved using 2 mg/kg lidocaine 2% alone, diluted with saline to a volume of 25 ml. In the LD group, IVRA was achieved using 2 mg/kg lidocaine 2% along with 0.5 mg/kg dexmedetomidine diluted with saline to a volume of 25 ml. The motor and sensory block onset and recovery times were assessed. Tourniquet pain and sedation score were assessed intraoperatively and postoperatively. The quality of anesthesia and the duration of analgesia were also recorded.
Sensory and motor block onset times were shorter and recovery times were prolonged in the LD group. The quality of anesthesia was better in the LD group, and the fentanyl dose required intraoperatively was also lower in the LD group. The duration of postoperative analgesia was longer and the doses of lornoxicam required were lower in the LD group.
A safe intravenous dose of lidocaine can be used for IVRA for superficial hand surgery, and the addition of 0.5 mg/kg dexmedetomidine shortened the onset times for both sensory and motor blockade and improved the quality of anesthesia, with prolonged postoperative analgesia time.
Keywords: dexmedetomidine, intravenous regional anesthesia, lidocaine
|How to cite this article:|
Abdelkader AA, Kasem AA, Rayan A. Addition of dexmedetomidine to a safe intravenous dose of lidocaine for intravenous regional anesthesia. Ain-Shams J Anaesthesiol 2015;8:664-9
|How to cite this URL:|
Abdelkader AA, Kasem AA, Rayan A. Addition of dexmedetomidine to a safe intravenous dose of lidocaine for intravenous regional anesthesia. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Jun 25];8:664-9. Available from: http://www.asja.eg.net/text.asp?2015/8/4/664/172765
| Introduction|| |
Intravenous regional anesthesia (IVRA) is a simple and reliable type of regional anesthesia. It was introduced for the first time by Karl August Bier, professor of surgery in Berlin, in 1908. However, it did not become popular immediately as it was complicated, requiring meticulous exsanguination with Esmarch bandages and the use of special equipment; most importantly, an operative procedure to locate the vein was necessary. The popularization of Bier's block can be ascribed to Holmes of Oxford, England, 1963. He utilized lidocaine for the first time and introduced several modifications, including a second cuff and a subcutaneous band of local anesthetic to control tourniquet pain  .
Although this technique is widely used because of its simplicity and reliability, it has been limited by tourniquet pain, lack of postoperative analgesia, and local anesthetic toxicity  . To improve the quality of IVRA block, various additives to local anesthetics were used, including opioids, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and also ketamine, to improve the quality of the intraoperative as well as the postoperative analgesia. However, the results were not consistent  .
After a Medline search we found that in most of the studies the lowest lidocaine dose used for IVRA was 3 mg/kg. Such a dose can induce systemic toxicity in case of tourniquet malfunction or early deflation. On using a lower dose of lidocaine, systemic toxicity might not happen. However, the effectiveness of such a lower dose has not been demonstrated before (with local anesthetic alone or with additives)  .
a-2-Adrenergic receptor (adrenoceptor) agonists have been the focus of interest as they have sedative, analgesic, and perioperative sympatholytic and cardiovascular stabilizing effects, with reduced anesthetic requirements ,,,, . Studies investigating the addition of clonidine to the local anesthetic solution in IVRA have demonstrated decreased tourniquet pain and improved postoperative pain relief, without adverse effects , .
Dexmedetomidine, a potent a-2-adrenoceptor agonist, is approximately eight times more selective than clonidine toward the a-2-adrenoceptors  . It has sedative and analgesic properties and has been shown to decrease anesthetic requirements by up to 90% ,,,, . To our knowledge, only two studies were published demonstrating the effect of dexmedetomidine when added to lidocaine. However, in both studies a full dose of lidocaine was used , .
This study was designed to evaluate the effectiveness of dexmedetomidine when added to low-dose (safe dose) lidocaine in providing effective analgesia for superficial hand surgery.
| Patients and methods|| |
This study was conducted in the day-surgery unit of King Abdul-Aziz Airbase Hospital (Dhahran, KSA). After obtaining approval from the Ethics Committee of the hospital, 50 adult patients with ASA I or II and undergoing elective superficial hand surgery, who gave written informed consent, were enrolled in this prospective double-blind study. Patients with sickle-cell disease, Reynaud's disease, or a history of allergic reaction to local anesthetics, and those refusing the IVRA technique or in whom venipuncture was difficult were excluded.
After the patients had been taken to the operative room, mean arterial blood pressure (MAP), peripheral oxygen saturation (SpO 2 ), and heart rate (HR) were monitored. Before establishing the anesthetic block, two cannulae were placed: one 22-G cannula in a vein on the dorsum of the operative hand and the other 18-G cannula in the other hand for crystalloid infusion. The operative arm was elevated for about 3 min and then exsanguinated with an Esmarch bandage, and a pneumatic tourniquet was placed around the upper arm, and the proximal cuff was inflated to 300 mmHg. Circulatory isolation of the operative arm was verified by inspection of the hand, absence of radial pulse, and loss of pulse oximetry tracing of the ipsilateral index finger. Patients were allocated randomly into two groups by means of the closed envelop technique.
IVRA was achieved using 2 mg/kg lidocaine 2% (Lidocaine 2%, PSI) diluted with saline to a total volume of 25 ml in the lidocaine group (group L, n = 25) or 2 mg/kg lidocaine 2% plus 0.5 mg/kg dexmedetomidine (Precedex 200 mg/2 ml; 100 Abbott Park Road, Abbott Park, Illinois 60064-3500) diluted with saline to a total volume of 25 ml in the dexmedetomidine group (group LD, n = 25). The solution was injected over 90 s by an anesthesiologist blinded to the injected drugs. The concentration of the solution after dilution was calculated and recorded.
The sensory block was assessed by a pinprick performed with a 25-G short-beveled needle at 30 s intervals by a blinded observer, starting 6 min after injection. Patient response was evaluated in the dermatomal sensory distribution of the ulnar (hypothenar eminence), median (thenar eminence), and radial (first web space) nerves and recorded. Motor function was assessed by asking the participant 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 the study drug to complete sensory block achieved in all dermatomes, and motor block onset time was the time elapsed from injection of the study drug to complete motor block.
After sensory block was achieved, the distal cuff was inflated followed by the release of the proximal tourniquet and the operation was then started.
MAP, HR, and SpO 2 were recorded before and after tourniquet application and then every 5 min after the injection of anesthetic. Hypotension (20% decrease from baseline value) was treated with intravenous ephedrine (5 mg/ml bolus), and the total dose of ephedrine was calculated. Bradycardia (20% decrease from baseline value or <50 bpm) was treated with intravenous atropine 0.5 mg, and arterial oxygen desaturation (<91%) was treated with O 2 supplementation through a nasal cannula.
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 the degree of sedation (the Ramsay sedation scale 1- 6: 1 = patient is anxious and agitated or restless, or both; 2 = patient is cooperative, oriented, and tranquil; 3 = patient responds to commands only; 4 = patient exhibits brisk response to light glabellar tap or loud auditory stimulus; 5 = patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus; and 6 = patient exhibits no response) measured before and after tourniquet application, and 5, 10, 15, 20, 30, and 40 min after the injection of the anesthetic.
Midazolam 1 mg increment up to a maximum of 3 mg was used for intraoperative sedation trying to maintain the patient at level 2-3 on the Ramsay sedation scale. Supplementary intraoperative analgesia in the form of intravenous bolus of fentanyl 0.5 mg/kg was provided whenever patients reported inadequate analgesia and was repeated as needed up to a total dose of 2 mg/kg. If patients still felt pain, general anesthesia was given.
At the end of the operation, the quality of the anesthesia was assessed on the basis of the 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.
After the operation, the surgeon, who was not aware what medication was given, was asked to qualify the operative conditions on the basis of the following numeric scale: 0 = unsuccessful; 1 = poor; 2 = acceptable; and 3 = perfect.
The tourniquet was deflated immediately by cyclic deflation technique at the end of the surgery, regardless of the tourniquet time. Sensory recovery time (time elapsed after tourniquet deflation up to recovery of pain in all dermatomes determined by pinprick test) and motor block recovery time were noted.
Assessment of pain scores was made on the basis of the VAS. Starting from tourniquet deflation, MAP, HR, VAS, and degree of sedation level values were recorded at 30 min intervals until the discharge of the patient home from the day-surgery unit. Xefo (8 mg, Nycomed, 60 Baylis Road, Melville, NY 11747) was given intravenously on recovery (rescue analgesia) when VAS was 4 or greater. Patients were instructed to receive Lornoxicam 8 mg/12 h orally in case of pain, and the total amount of Lornoxicam for the first 48 h was recorded by telephone call. The duration of postoperative analgesia was the time between tourniquet release and the first intravenous intake of lornoxicam. During the study period, any local or systemic complications were recorded.
The primary outcome in this study was the number of patients in the LD group with effective short sensory block time, and secondary outcomes included the quality of the anesthesia, intraoperative fentanyl requirements, the duration of postoperative analgesia, and lornoxicam requirements.
Using PASS for sample size calculation, it was determined that a sample size of 23 patients per group was expected to have a power of 80% to detect a difference of 5.1 min in sensory block onset time between the two groups with estimated group SDs of 6.0 with a significance level (a) of 0.05000 using a two-sided two-sample t-test. Twenty-five patients per group were included to replace any dropouts.
Statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc, Chicago, Illinois, USA). Data were expressed as mean values ± SD and comparisons were made using the unpaired t0‐test, medians and interquartile ranges are quoted for skewed data, and the Mann-Whitney U‐test. Discrete (categorical) variables were represented as numbers (%) and were analyzed using the c2 -test, with P values less than 0.05 considered statistically significant.
| Results|| |
There were no significant differences in age, sex, weight, height, duration of surgery, type of surgery, and tourniquet time [Table 1]. Among the patients, none was excluded from the study because of technical failure.
As regards the average concentration of the solution used in both groups, there was no statistically significant difference between the two groups (0.56 ± 0.16% in the LD group vs. 0.61 ± 0.18% in the L group).
It was found that the MAP, HR, and SpO 2 values at any intraoperative and postoperative period were comparable, with no statistically significant difference between the two groups. However, no treatment was required for hypotension or bradycardia in any patient.
Sensory and motor block onset times were significantly shorter in the LD group compared with the L group. The sensory and motor block recovery times were also significantly prolonged in the LD group compared with the L group [Table 2].
The quality of anesthesia was significantly better in the LD group than in the L group, and the amount of fentanyl required intraoperatively was significantly lower in the LD group than in the L group. The duration of postoperative analgesia was significantly longer in the LD group than in the L group. In addition, the total amount of lornoxicam required was significantly lower in the LD group than in the L group [Table 3].
|Table 3 Quality of anesthesia, the duration of analgesia, and the amount of intraoperative and postoperative analgesic|
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As regards sedation, it was found that there was no significant difference between the two groups intraoperatively, but sedation score was significantly higher in the LD group than in the L group during the postoperative period [Figure 1]. However, no patient required admission, and the time to discharge home was not different between the two groups.
|Figure 1: Postoperative Ramsay sedation scale in both groups. Boxes are median (interquartile range) and whiskers are minimum and maximum|
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There was a significant difference between groups when compared for VAS scores for tourniquet pain after tourniquet inflation at 5, 10, 15, 20, and 30 min; there was a significantly lower VAS in the LD group (P < 0.001). In addition, there were significant differences between groups in terms of postoperative VAS scores [Table 4] and [Table 5].
| Discussion|| |
Systemic toxicity of local anesthetics may be a life-threatening situation. It typically manifests as central nervous system (CNS) toxicity (tinnitus, disorientation, and ultimately, seizures) or cardiovascular toxicity (hypotension, dysrhythmias, and cardiac arrest). The dose capable of causing CNS symptoms is typically lower than the dose and concentration that results in cardiovascular toxicity. This is because the CNS is more susceptible to local anesthetic toxicity compared with the cardiovascular system  .
The earliest signs of systemic toxicity are mostly caused by blockade of inhibitory pathways in the cerebral cortex. This allows for disinhibition of facilitator neurons, leading to excitatory cell preponderance and unopposed excitatory nerve activity. That is why initial subjective symptoms of CNS toxicity include excitatory signs, such as lightheadedness and dizziness, difficulty focusing, tinnitus, confusion, and circumoral numbness  .
Our study demonstrated that the addition of 0.5 mg/kg dexmedetomidine to lidocaine for IVRA allowed the use of a low-lidocaine dose to the safe intravenous dosage limit, as a consequence decreasing the likely risk of local anesthetic toxicity in case of malfunction or early release of the tourniquet. It also improved the quality of anesthesia, provided satisfactory intraoperative analgesia, and extended postoperative analgesia, with no side effects reported.
Centrally acting a-2-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, a-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 a-2-adrenergic agonist  . In addition, a-2-adrenergic receptors located at nerve endings may have a role in the analgesic effect of the drug by preventing norepinephrine release  .
a-2-adrenergic agonists produce sedation, and electroencephalographic studies confirm the increase in stage I and II sleep. The hypnotic response most probably is mediated by the activation of a-2-adrenoceptors located in the locus coeruleus, which are coupled through a pertussis toxin-sensitive G protein to a change in conductance through an ion channel. Inhibition of adenylate cyclase may also be involved in the hypnotic response  .
In previous clinical studies, clonidine has been used as an adjuvant for IVRA. Gentili et al.  were the first to report the efficacy of IVRA clonidine in decreasing tourniquet pain. Lurie et al.  evaluated the efficacy of clonidine at a dose of 1 mg/kg added to IVRA-lidocaine in decreasing the onset of severe tourniquet pain and found that it delayed the onset time. Reuben and Sklar  evaluated the efficacy and safety of administering IVRA with an addition of 1 mg/kg clonidine in the management of complex regional pain syndrome of the knee and demonstrated lower pain scores and lower analgesic consumption in those patients. Gorgias et al.  found that the addition of 1 mg/kg clonidine to lidocaine for IVRA delayed the onset of unbearable tourniquet pain and decreased analgesic consumption for tourniquet pain relief.
Dexmedetomidine is approximately eight times more selective toward the a-2-adrenoceptors compared with clonidine  . It produces sedation, analgesia, and anxiolysis. It decreases anesthetic requirements by up to 90%. It also significantly reduced rescue analgesic requirement compared with placebo in postoperative patients ,,,, . Acute dexmedetomidine intravenous 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  . Its sedative, proanesthetic, and proanalgesic effects at 0.5-2 mg/kg given intravenously arise mainly from its ability to blunt the central sympathetic response. It also minimizes opioid-induced muscle rigidity, lessens postoperative shivering, has hemodynamic stabilizing effects, and causes minimal respiratory depression  .
Jaakola  assessed the safety and efficacy of IV dexmedetomidine as a premedication before IVRA. She found that 1 m/kg dexmedetomidine was an effective premedication before IVRA because it reduced patient anxiety, sympathoadrenal responses, and opioid analgesic requirements; however, it did not reduce tourniquet pain  .
In our study, we found that the addition of 0.5 mg/kg dexmedetomidine to lidocaine for IVRA leads to a significant decrease in the sensory and motor block onset times. It was also found that sensory and motor block recovery times were significantly prolonged in this group. Our study's results were in agreement with those of Memis et al.  . In contrast to these results, Esmaoglu et al.  did not show any differences in the sensory and motor block onset and regression times between the two groups, although they used 1 mg/kg of dexmedetomidine.
In our study, we observed that dexmedetomidine improved the quality of the anesthesia and decreased the postoperative analgesic requirements. This improvement in quality may be due to the peripheral action of the dexmedetomidine on the a-2-adrenergic receptors subtype, whereas less analgesic requirements and occurrence of sedation after release of the tourniquet may be due to the central action of dexmedetomidine. The same was concluded by Memis et al.  and Esmaoglu et al.  in their studies.
As it is known that intravenous injection of dexmedetomidine can induce hypotension and bradycardia in a dose-dependent manner, Memis et al.  concluded that the use of a small dose of dexmedetomidine (0.5 mg/kg) and atropine that was given as premedication might presumably have resulted in a lesser degree of such side effects. However, no such side effects were observed in our study, although we did not use atropine as a premedication. The same was observed by Esmaoglu et al.  even with the addition of 1 mg/kg dexmedetomidine to lidocaine without atropine as a premedication  . From our results and from the results of Esmaoglu et al.  , we can conclude that dexmedetomidine used as an additive to a local anesthetic during IVRA does not result in hypotension or bradycardia and no atropine premedication is required; further studies are needed to support this observation.
| Conclusion|| |
The addition of 0.5 mg/kg dexmedetomidine to lidocaine for IVRA shortens the onset times for both sensory and motor blockade, improves the quality of the anesthesia and extends postoperative analgesia time, and allows reduction of the lidocaine dose used for IVRA to the safe dose. It also allows early tourniquet deflation without causing adverse effects regardless of the tourniquet time.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Brill S, Middelton W, Brill G, Fisher A. Bier's block; 100 years old and still going strong!. Acta Anaesthesiol Scand 2004; 48:117-122.
Johnson CN. Intravenous regional anesthesia: new approaches to an old technique. CRNA 2000; 11:57-61.
Prieto-Alvarez P, Calas-Guerra A, Fuentes-Bellido J, Martínez-Verdera E, Benet-Català A, Lorenzo-Foz JP. Comparison of mepivacaine and lidocaine for intravenous regional anaesthesia: pharmacokinetic study and clinical correlation. Br J Anaesth 2002; 88:516-519.
Bigat Z, Karsli B, Boztug N, Cete N, Ertok E. Comparison of the effect of low-dose ropivacaine and lidocaine in intravenous regional anaesthesia: a randomised, double-blind clinical study.. Clin Drug Investig 2005; 25:209-214.
Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists.. Anesthesiology 2000; 93:1345-1349.
Aho M, Erkola O, Kallio A, Scheinin H, Korttila K. Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg 1992; 75:940-946.
Jaakola ML, Ali-Melkkilä T, Kanto J, Kallio A, Scheinin H, Scheinin M. Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery. BrJ Anaesth 1992; 68:570-575.
Kalso EA, Pöyhiä R, Rosenberg PH. Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist. Pharmacol Toxicol 1991; 68:140-143.
Aho MS, Erkola OA, Scheinin H, Lehtinen AM, Korttila KT. Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg 1991; 73:112-118.
Gentili M, Bernard JM, Bonnet F. Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. Anesth Analg 1999; 88:1327-1330.
Reuben SS, Sklar J. Intravenous regional anesthesia with clonidine in the management of complex regional pain syndrome of the knee. J Clin Anesth 2002; 14:87-91.
Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000; 59: 263-268; discussion 269-270.
Memiþ D, Turan A, Karamanlioðlu B, Pamukçu Z, Kurt I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg 2004; 98:835-840.
Esmaoglu A, Mizrak A, Akin A, Turk Y, Boyaci A. Addition of dexmedetomidine to lidocaine for intravenous regional anaesthesia. Eur J Anaesthesiol 2005; 22:447-451.
Feldman HS. Toxicity of local agents. In: Rice SA, Fish KJ Eds. Anaesthetic toxicity
. New York, NY: Raven Press; 1995.
Cox B, Durieux ME, Mrcus MA. Toxicity of local anaesthetics. Best Pract Res Clin Anaesthesiol 2003; 17:111-136.
Maze M, Regan JW. Role of signal transduction in anesthetic action. Alpha 2 adrenergic agonists. Ann N Y Acad Sci 1991; 625:409-422.
Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 1991; 251:1608-1610.
Lurie SD, Reuben SS, Gibson CS, DeLuca PA, Maciolek HA. Effect of clonidine on upper extremity tourniquet pain in healthy volunteers. Reg Anesth Pain Med 2000; 25:502-505.
Gorgias NK, Maidatsi PG, Kyriakidis AM, Karakoulas KA, Alvanos DN, Giala MM. Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine. Reg Anesth Pain Med 2001; 26:512-517.
Dyck JB, Shafer SL. Dexmedetomidine pharmacokinetics and pharmacodynamics. Anaesth Pharmacol Rev 1993; 1:238-245.
Weinbroum AA, Ben-Abraham R. Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. Eur J Surg 2001; 167:563-569.
Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 1994; 6:204-211.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]