|Year : 2016 | Volume
| Issue : 4 | Page : 576-583
Comparison between dexmedetomidine and verapamil as an adjuvant to local anesthesia in intravenous regional anesthesia in upper limb orthopedic surgery: a randomized double-blind prospective study
Medhat M Messseha Gerges
Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||22-Dec-2015|
|Date of Acceptance||24-Feb-2016|
|Date of Web Publication||12-Jan-2017|
Medhat M Messseha Gerges
Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, 35516
Source of Support: None, Conflict of Interest: None
The use of intravenous regional anesthesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade.
This randomized double-blind prospective study was designed to compare the effectiveness of adding dexmedetomidine (α2 adrenoceptor agonist) or verapamil (calcium channel antagonist) as an adjunct to lidocaine in upper limb orthopedic surgery.
Patients and methods
Sixty adult patients scheduled for elective upper limb orthopedic surgery were divided into three groups: the lidocaine group, in which patients received 3 mg/kg of lidocaine 2% diluted with saline to a total volume of 40 ml; the lidocaine dexmedetomidine group, in which patients received 0.5 µg/kg of dexmedetomidine plus 3 mg/kg of lidocaine 2%; and the lidocaine verapamil group, in which patients received 2.5 mg of verapamil plus 3 mg/kg of lidocaine 2%. The onset and duration of sensory and motor block were recorded. Postoperative Visual Analog Score, onset of tourniquet pain, duration of analgesia, and total analgesic requirements at the 12th postoperative hour were monitored.
Adding dexmedetomidine or verapamil to lidocaine causes faster onset and prolonged recovery of sensory and motor block and improvement of postoperative analgesia, without causing side effects compared with lidocaine alone.
The use of either verapamil or dexmedetomidine as an adjuvant to lidocaine solution causes equal improvement of the quality of anesthesia in intravenous regional anesthesia of upper limb orthopedic surgeries.
Keywords: dexmedetomidine, intravenous regional anesthesia, lidocaine, verapamil
|How to cite this article:|
Messseha Gerges MM. Comparison between dexmedetomidine and verapamil as an adjuvant to local anesthesia in intravenous regional anesthesia in upper limb orthopedic surgery: a randomized double-blind prospective study. Ain-Shams J Anaesthesiol 2016;9:576-83
|How to cite this URL:|
Messseha Gerges MM. Comparison between dexmedetomidine and verapamil as an adjuvant to local anesthesia in intravenous regional anesthesia in upper limb orthopedic surgery: a randomized double-blind prospective study. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2018 Oct 22];9:576-83. Available from: http://www.asja.eg.net/text.asp?2016/9/4/576/198261
| Introduction|| |
Regional anesthesia can provide a combination of excellent localized postoperative analgesia with minimal systemic impairment. Intravenous regional anesthesia (IVRA) is a safe, technically simple, reliable, and effective technique for short surgical procedures in the duration of 60–90 min in hand and forearm operations. It is an ideal technique for short operative procedures on extremities, performed on a day-care basis, with success rates between 94 and 98% . IVRA was first used by August K.G. Bier in 1908 through intravenous injection of prilocaine after arterial occlusion with a tourniquet for the upper limb surgery. In the 1960s, this procedure gained maximum popularity when Holmes  used lidocaine instead of prilocaine. This is a type of regional anesthesia that isolates the limb from systemic circulation using pneumatic tourniquet pressure to the proximal extremity .
Bier’s block (IVRA) has many advantages such as rapid onset, simplicity, low costs, reduced operating room time by placing the block preoperatively, and avoidance of unnecessary complications of general anesthesia. However, recovery from the anesthetic facilitates early ambulatory patient discharge . In contrast, common problems associated with IVRA are tourniquet pain and postoperative poor analgesia after tourniquet release compared with other peripheral nerve blocks .
In recent years, it has gained modification with the addition of various adjuncts to local anesthetic solution in an attempt to improve the quality of IVRA block to facilitate the onset, maintain adequate muscle relaxation, decrease tourniquet pain, and increase the efficacy and duration of postoperative analgesia . Because of their side effects, their uses are limited. Opioids are the mainstay of treating acute postoperative pain when added to local anesthetics and has been associated with many adverse events, such as nausea and vomiting, mood alteration, respiratory depression, and pruritus. Nonopioid analgesics (NSAIDs) can have a morphine-sparing effect and reduce these side effects. However, these drugs are associated with other adverse event profiles, including renal impairment and gastrointestinal hemorrhage . Other adjuncts such as epinephrine, bicarbonate, clonidine, dexamethasone, muscle relaxants, dexmedetomidine, magnesium, neostigmine, and ketamine, have been injected concomitantly with local anesthetic solution with varied effects .
Dexmedetomidine is a potent α2 adrenoceptor agonist and approximately eight times more selective toward the α2 adrenoceptors compared with clonidine. Dexmedetomidine have perioperative sympatholytic and cardiovascular stabilizing effects besides its sedative, analgesic, and reduced anesthetic requirements up to 90% .
Verapamil is a dihydropiridine L-type voltage-gated calcium channel antagonist. There is growing evidence suggesting that calcium ions play a vital role in analgesia mediated by local anesthetics and are involved in endogenous regulation of pain sensitivity . Increases in intracellular calcium are associated with central sensitization after noxious stimuli, suggesting that voltage-gated calcium channels have an important role and affect the transmission of nociceptive impulses . Spinal verapamil with lidocaine produced prolonged potent pain relief with adequate motor block .
This study was designed to compare the effectiveness of adding dexmedetomidine or verapamil as an adjunct to lidocaine in IVRA. We planned to investigate the onset and recovery time, intraoperative and postoperative hemodynamic variables, pain, and the probable side effects.
| Patients and methods|| |
This prospective clinically randomized double-blind study was carried out on 60 adult patients, aged 30–50 years, American Society of Anesthesiologists physical status I and II, scheduled for elective upper limb (forearm and hand) orthopedic surgery at Mansoura University Hospitals. The protocol of the study was approved by the responsible ethics committee and authorities. Patients were subjected to a complete preanesthetic examination and were informed about the anesthetic procedure and the use of the Visual Analog Scale (VAS) during both intraoperative and postoperative period after informed written consent was obtained from patients. Data were collected over the first 4 months in 2015.
Exclusion criteria were as follows: weight below 60 or above 100 kg; patient refusal; infection at the site of injection; receiving anticoagulants or calcium channel blockers; a history of peripheral neuropathies; presence of cardiac conduction abnormalities; coagulation disorders; hypersensitivity to local anesthetic agents; or major liver or kidney disease. Other exclusion criteria were Raynaud disease, sickle cell anemia, coronary artery disease, uncontrolled hypertension, congestive heart failure, and known allergy to calcium antagonists.
Preoperative sedation was achieved 30 min before surgery with midazolam 5 mg and atropine 1 mg through an intravenous cannula in the nonoperative hand. The patients were randomly divided into three groups of 20 patients each using the closed envelops technique. In the preoperative area, routine pulse oximetry (SpO2), heart rate (HR), ECG, and noninvasive mean arterial blood pressure (MAP) were monitored and recorded for all patients (Datex-Ohmeda S/5; GE Health Care, Helsinki, Finland). Before performing the block, another cannula was placed in a vein on the dorsum of the operative hand and secured. The other line in the opposite hand was for intravenous crystalloid infusion.
A double-cuffed pneumatic tourniquet (Tourniquet 2800 ELC, UMB; Medizintechnik GmbH, Sulz am Neckar, Germany) was placed around the upper operative arm, and the arm was elevated for 3–5 min and then exsanguinated with Esmarch bandage, and the proximal cuff was inflated to 250 mmHg, confirmed by inspection and absence of radial pulse.
Group I (the lidocaine group) (L) (n=20) patients received 3 mg/kg of lidocaine 2% (2% lidocaine Hcl; Hospira, Lake Forest, Illinois, USA) diluted with saline to a total volume of 40 ml. Group II (the lidocaine dexmedetomidine group) (LD) (n=20) patients received 0.5 µg/kg of dexmedetomidine (Precedex 200 µg/2 ml; Abbott, North Chicago, Illinois, USA) plus 3 mg/kg of lidocaine 2% diluted with saline to a total volume of 40 ml. Group III (the lidocaine verapamil group) (LV) (n=20) patients received 2.5 mg of verapamil (izoptomil ampoule 5 mg/2 ml; The Arab Drug Company, Cairo, Egypt) plus 3 mg/kg of lidocaine 2% diluted with saline to a total volume of 40 ml. The solutions were injected over 90 s by an anesthesiologist blinded to the injected drugs.
After performance of the block, the following parameters were observed: onset time of sensory blockade (time between injection and total abolition of pinprick response); patients were evaluated every 5 min using the pinprick test. Time for onset of the complete motor blockade (interval between the times of injection of the study solution until the time the patient was not able to move his fingers) was recorded. All observations were made in the four major nerve distribution areas (radial, median, ulnar, and musculocutaeneous).
After achievement of motor and sensory block, the distal cuff was inflated to 250 mmHg followed by the release of the proximal tourniquet. The tourniquet cuff was deflated after 60 min or at the end of surgery, with total duration not exceeding 90 min.
Hemodynamic parameters (HR and MAP) were monitored and recorded before and after inflation of the tourniquet, at 5, 10, 20, 40, and 60 min after the injection of anesthetic by an independent anesthesiologist not involved in the study. Hypotension (20% decrease from baseline reading) was treated with bolus 3–9 mg ephedrine intravenously, and bradycardia (20% decrease from baseline reading) was treated with 0.5 mg atropine intravenously.
Tourniquet pain was assessed using the 10 cm marked VAS (0=‘no pain’ and 10=‘worst pain imaginable’) , measured after the application of second tourniquet to assess the need for analgesia. Boluses of fentanyl 0.5 µg/kg were given if VAS was more than 3. Total fentanyl consumption was recorded.
After deflation of the tourniquet postoperatively, vital parameters (HR and MAP) were monitored at 1, 2, 6, and 12 h. Observations were made every 30 min to evaluate the duration of the sensory blockade (time between onset and return of pinprick response) and the duration of the motor blockade (return of complete muscle power). VAS scores were recorded at 1, 2, 6, and 12 h after the end of the operation. If VAS scores were more than 3, the patient received 0.5 µg/kg of fentanyl. Duration of analgesia (time between onset of action and first analgesic required after tourniquet deflation) and total postoperative fentanyl consumption were recorded.
Any adverse effects were recorded during the study period, such as dizziness, hallucinations, tinnitus, postoperative nausea and vomiting, respiratory depression (<10/min), hypoxemia (SpO2, 90%), hypotension (blood pressure, 20% below baseline), and bradycardia (HR<60/min).
Power of study: in a previous study, the incidence of complete sensory block at 5 min in the IVRA was about 40%. Assuming α (type I error)=0.05 and β (type II error)=0.2 (power=80%), 18 patients were required in each group to detect a difference of 30% between the groups. Allowing for patients lost to analysis, 20 patients were assigned to each group. Statistical analyses were performed using SPSS, version 22 (IBM; SPSS Inc., Chicago, Illinois, USA). Data were tested for normality using the Kolmogorov–Smirnov test. Continuous data of normal distribution were presented as mean±SD and were analyzed with the analysis of variance with the post-hoc Tukey test. A P value less than 0.05 was considered statistically significant.
| Results|| |
All blocks were either performed by the author or carried out under his supervision. No patient was excluded from the study because of failed blocks. The demographic data in all groups as regards age, weight, sex, duration of surgery, and duration of tourniquet did not show any statistically significant difference between groups, as shown in [Table 1].
Hemodynamics in the form of HR and MAP in all groups are given in [Table 2] and [Table 3], respectively; there was no statistically significant difference between groups at intraoperative and postoperative period up to 12 h.
|Table 2: Perioperative heart rate (beat/min) of the studied groups (n=20)|
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|Table 3: Perioperative mean arterial blood pressure (mmHg) of the studied groups (n=20)|
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The onset and duration of sensory and motor blocks in all groups are given in [Table 4]. The onset of sensory and motor blocks were statistically shorter in the LD and LV groups in comparison with the L group. Sensory and motor block recovery times after deflation of the tourniquet were statistically prolonged in the LD and the LV group in comparison with the L group.
|Table 4: Onset and duration of sensory and motor block of the studied groups (n=20)|
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The onset of tourniquet pain was significantly delayed in both the LD and LV groups when compared with the L group. Duration of analgesia was significantly prolonged in the LD and LV groups when compared with the L group. The total required dose of fentanyl within 12 h postoperatively was statistically significantly lower in the LD and LV groups when compared with the L group ([Table 5]). VAS score after tourniquet release was statistically significantly lower in the LD and LV groups when compared with the L group in the first and second postoperative hours ([Table 6]).
|Table 5: Onset of tourniquet pain, duration of analgesia, time for first analgesic requirement, and total fentanyl requirement in the 12th postoperative hours of the studied groups (n=20)|
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Oxygen saturation (SpO2) was within the acceptable clinical range (96% mean value through study). There were no signs of central nervous system or cardiovascular toxicity and no other side effects were seen after deflation of tourniquet and postoperative period. No patient needed treatment for bradycardia or hypotension.
| Discussion|| |
The present study demonstrated that the addition of either dexmedetomidine 0.5 µg/kg or verapamil 2.5 mg to lidocaine for IVRA of upper limb improved the quality of anesthesia, resulting in faster onset of sensory and motor block, lengthened recovery of sensory and motor blockade, and improved postoperative analgesia without causing side effects, as compared with lidocaine alone.
Peripheral nerve blocks offer the potential benefits of prolonged analgesia, with fewer side effects, greater patient satisfaction, and faster functional recovery after surgery . Gentili et al.  were the first to report the efficacy of IVRA clonidine in decreasing tourniquet pain. Gorgias et al.  reported that the 1 µg/kg of clonidine as adjunct to lidocaine for IVRA delayed the onset of unbearable pain of tourniquet and decreased analgesic consumption for relief of tourniquet pain. Lurie et al.  found that 1 µg/kg of clonidine delayed the onset time and decreased tourniquet pain when added to lidocaine for IVRA. Dexmedetomidine is more selective toward the α2 adrenoceptors compared with clonidine (approximately eight times) . Therefore, dexmedetomidine in IVRA may be effective as clonidine.
α2-Adrenergic agonists produce sedation and analgesia; stimulation of α2-adrenergic receptors prevent norepinephrine release at nerve endings, which may explain the role of the analgesic effect of the drug . Perioperative administration of dexmedetomidine decreased the requirements for nonopioid or opioid analgesics .
In the present study, addition of dexmedetomidine to lidocaine led to a reduction in tourniquet pain and a decrease in the total fentanyl consumption. This is in agreement with the findings of Jaakola , who evaluated that effectiveness of dexmedetomidine 1 µg/kg as a premedication before IVRA because of its sedative and analgesic properties, which led to reduced anxiety, opioid analgesic requirements, and sympathoadrenal responses, but it did not reduce pain of tourniquet. Dexmedetomidine prolonged the effect of ropivacaine in posterior tibial nerve sensory blockade , bupivacaine in supraclavicular brachial plexus block , and ropivacaine in interscalene brachial plexus blocks .
Dexmedetomidine intravenous administration may produce a slight decrease in both HR and MAP from baseline  because of its ability to decrease the central sympathetic response; atropine premedication might result in a lesser degree of such side effects. Dexmedetomidine at a dose of intravenous 0.5–2 µg/kg provides sedative, proanalgesic, and proanesthetic effects, causes minimal respiratory depression, decreases muscle rigidity induced by opioid, has hemodynamic stabilizing effects, and lessens postoperative shivering .
The primary action of local anesthetics is reversible block conduction of the nerve impulses by preventing the permeability of the nerve membrane to the sodium ions and depressing influx of calcium ions at concentration required to block nerve conduction. Calcium movement is essential for the normal sensory processing and plays a role in axonal conduction and synaptic transmission . Most of the local anesthetics such as lidocaine, amylocaine, procaine, or cinchocaine have the ability to inhibit calcium uptake and the calcium ion-activated ATPase activity of sarcoplasmic reticulum vesicles. Inhibition of calcium efflux from the sarcoplasmic reticulum was explained by incorporation of these amphophilic local anesthetic drugs into the lipid layer, interaction with calcium ion binding sites on membrane phospholipids, or direct interaction with a calcium channel . Therefore, calcium channel blockers potentiate the analgesic effect of local anesthetics and acts primarily by means of vasodilatation and reduction of peripheral vascular resistance .
Many studies demonstrated calcium channel blockers along with local anesthetics used in IVRA. Nowycky et al.  reported the evidence of three distinct types of calcium channels in sensory neurons − namely, the L, T, and N types. Of these, the L and N types of channels have a significant role in regulating neurotransmitter release from neurons. The N type has much more potent antinociceptive effects compared with the L type. N type channel blockers were not clinically suitable for use because of their severe neurotoxicity. Hara et al.  showed that the L-type channel blockers verapamil and diltiazem produced both somatic and visceral pain relief in a dose-dependent manner, suggesting the relevance of L-type channel blockers in pain management. Because calcium channel blockers are known to potentiate the actions of local anesthetics and opioids, investigators have evaluated verapamil as an adjunct for plexus blockade . Iwasaki et al.  demonstrated that local sensory block produced by lidocaine injection at the tail base was potentiated by verapamil, diltiazem, and nicardipine in a dose-dependent manner in rats. Moreover, intrathecal verapamil alone did not produce motor or sensory block. However, in combination with lidocaine or tetracaine, the block produced was more potent and of longer duration than that produced by the local anesthetic alone in rats . Brachial plexus administration of verapamil 2.5 mg increased the duration of surgical anesthesia by ∼90 min when added to lidocaine with epinephrine axillary block .
Some researchers have suggested that the analgesic effect of calcium channel blockers is centrally and not peripherally mediated. Del Pozo et al.  found that subcutaneous calcium channel blockers failed to exhibit antinociceptive effects, but was clearly analgesic when administered through the intracerebroventricular route in rats. Choe et al.  demonstrated that the addition of calcium channel blockers to bupivacaine administered epidurally resulted in less postoperative analgesic requirement.
In the present study, there were no major hemodynamic alterations during the studied time for 12 h postoperatively, although it is well known that the systemic administration of calcium channel blockers cause myocardial depression leading to hypotension and bradycardia. This controversy may be due to the pharmacokinetic interaction of different drug solutions, such as changing pH and the temperature at injection site .
To the best of our knowledge, no previous study was published comparing the addition of calcium channel blocker, verapamil 2.5 mg, versus α2 agonist, dexmedetomidine 0.5 µg/kg, with lidocaine solution during Bier’s block. Nonsignificant difference was observed between the LD and LV groups as regards the onset and duration of sensory and motor block, onset of tourniquet pain, duration of analgesia, total dose of fentanyl requirement, and VAS score.
| Conclusion|| |
The present study showed that the addition of either verapamil 2.5 mg or dexmedetomidine 0.5 µg/kg to lidocaine solution causes equal improvement of the quality of anesthesia in IVRA of upper limb, faster onset and prolonged recovery of sensory and motor block, and improvement of postoperative analgesia without causing side effects as compared with lidocaine alone.
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| References|| |
Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg 2011;113:904–925.
Holmes C. Intravenous regional anaesthesia: a useful method of providing analgesia in the limbs. Lancet 1963;1:245–247.
Collins VJ. Principles of anaesthesiology. 3rd ed. Philadelphia, PA: Lea & Febiger; 1993:794–808.
Gerancher JC. Upper extremity nerve blocks. Anesthesiol Clin North America 2000;18:297–317.
Johnson CN. Intravenous regional anesthesia: new approaches to an old technique. CRNA 2000;11:57–61.
Kirksey MA, Haskins SC, Cheng J, Liu SS. Local anesthetic peripheral nerve block adjuvants for prolongation of analgesia: a systematic qualitative review. PLoS One 2015;10:e0137312.
Ng A, Parker J, Toogood L, Cotton BR, Smith G. Does the opioid-sparing effect of rectal diclofenac following total abdominal hysterectomybenefit the patient? Br J Anaesth 2002;88:714–716.
Culebras X, van Gessel E, Hoffmeyer P, Gamulin Z. Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes. Anesth Analg 2001;92:199–204.
Kamibayashi T, Maze M. Clinical uses of alpha-2-adrenergic agonists. Anesthesiology 2000;93:1345–1349.
Fassoulaki A, Sarantopoulos C, Zotou M. Nitrous oxide enhances the level of sensory block produced by intrathecal lidocaine. Anesth Analg 1997;85:1108–1111.
Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993;52:259–285.
Omote K, Iwasaki H, Kawamata M, Satoh O, Namiki A. Effects of verapamil on spinal anesthesia with local anesthetics. Anesth Analg 1995;80:444–448.
Gentili M, Bernard JM, Bonnet F. Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. Anesth Analg 1999;88:1327–1330.
Liu SS, Salinas FV. Continuous plexus and peripheral nerve blocks for postoperative analgesia. Anesth Analg 2003;96:263–272.
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.
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.
Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 1991;251:1608–1610.
Scheinin H, Jaakola ML, Sjövall S, Ali-Melkkilä T, Kaukinen S, Turunen J, Kanto J. Intramuscular dexmedetomidine as premedication for general anesthesia. Anesthesiology 1993;78:1065–1075.
Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 1994;6:204–211.
Rancourt MP, Albert NT, Cote M, Letourneau DR, Bernard PM. Posterior tibial nerve sensory blockade duration prolonged by adding dexmedetomidine to ropivacaine. Anesth Analg 2012;115:958–962.
Agarwal S, Aggarwal R, Gupta P. Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block. J Anaesthesiol Clin Pharmacol 2014;30:36–40.
Fritsch G, Danninger T, Allerberger K, Tsodikov A, Felder TK, Kapeller M et al.
Dexmedetomidine added to ropivacaine extends the duration of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone: a single-center, prospective, triple-blind, randomized controlled trial. Reg Anesth Pain Med 2014;39:37–47.
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.
Palade PT, Almers W. Slow calcium and potassium currents in frog skeletal muscle: their relationship and pharmacologic properties. Pflugers Arch 1985;405:91–101.
Iwasaki H, Ohmori H, Omote K, Kawamata M, Sumita S, Yamauchi M, Namiki A. Potentiation of local lidocaine induced sensory block by calcium channel blockers in rats. Br J Anaesth 1996;77:243–247.
Smith FL, Davis RW, Carter R. Influence of voltage-sensitive Ca++
channel drugs on bupivacaine infiltration anesthesia in mice. Anesthesiology 2001;95:1189–1197.
Nowycky MC, Fox AP, Tsien RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 1985;316:440–443.
Hara K, Saito Y, Krihara Y, Sakura S, Kosaka Y. Antinociceptive effects of intrathecal L-type calcium channel blockers on visceral and somatic stimuli in the rat. Anesth Analg 1998;87:382–387.
Reuben SS, Reuben JP. Brachial plexus anesthesia with verapamil and/or morphine. Anesth Analg 2000;91:379–383.
Fassoulaki A, Zotou M, Sarantopoulos C. Effect of nimodipine on regression of spinal analgesia. Br J Anaesth 1998;81:358–360.
Del Pozo E, Ruiz-García C, Baeyens JM. Analgesic effects of diltazem and verapamil after central and peripheral administration in the hot plate test. Gen Pharmacol 1990;21:681–685.
Choe H, Kim JS, Ko SH, Kim DC, Han YJ, Song HS. Epidural verapamil reduces analgesic consumption after lower abdominal surgery. Anaesth Analg 1998; 86: 786–790.
Sharma JP, Salhotra R. Tourniquets in orthopedic surgery. Indian J Orthop 2012;46:377–383.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]