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Current Anesthesiology Reports
Published in: Current Anesthesiology Reports 3/2019

01-09-2019 | Clonidine | Regional Anesthesia (P Kukreja, Section Editor)

Local Anesthetic Additives for Regional Anesthesia: a Review of Current Literature and Clinical Application

Authors: Promil Kukreja, Lisa MacBeth, Joel Feinstein

Published in: Current Anesthesiology Reports | Issue 3/2019

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Abstract

Purpose of Review

Improving perioperative pain management with regional anesthesia has become prevalent and extremely important, due in part to the opioid epidemic and increased emphasis on enhanced recovery after surgery (ERAS) protocols. Perineural catheters offer extended duration of nerve blockade as compared with single dose of local anesthetic at the cost of increased risk of catheter-related complications like displacement and higher infection rate. Also, many practices lack the infrastructure to manage catheters. We are continuously exploring options to extend block duration without catheters, and local anesthetic additives offer a viable option to prolong the benefits of plain local anesthetics.

Recent Findings

A recent randomized cross-over study has suggested that the efficacy of local anesthetic additives like dexamethasone on the duration of nerve block remains uncertain despite several supporting systematic reviews and meta-analysis data.

Summary

This article reviews current literature to provide clinically relevant information about common nerve block additives, describing rationale for their use, effect on block onset, extension of block duration, and safety profiles of the additives.
Literature
1.
•• Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011;113(4):904–25. This article is an evidence-based review of published literature involving continuous peripheral nerve block and its effect on postoperative analgesia, opioid-related side effects, and patient satisfaction. PubMed
2.
Yang S, Abrahams MS, Hurn PD, Grafe MR, Kirsch JR. Local anesthetic Schwann cell toxicity is time and concentration dependent. Reg Anesth Pain Med. 2011;36(5):441–51.
3.
•• Albrecht E, Kern C, Kirkham KR. A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks. Anaesthesia. 2015;70:71–83. This article reviewed the safety and efficacy of paerineural dexamethasone as an adjunct for peripheral nerve blockade. PubMed
4.
Williams BA, Butt MT, Zeller JR, Coffee S, Pippi MA. Multimodal perineural analgesia with combined bupivacaine-clinidine-buprenorphine-dexamethasone: safe in vivo and chemically compatible in solution. Pain Med. 2015;16(1):186–98.PubMed
5.
Choi S, Rodseth R, McCartney CJ. Effects of dexamethasone as local anesthetic adjuvant for brachial plexus block: a systemic review and meta-analysis of randomized trials. Br J Anaesth. 2014;112(3):427–39.PubMed
6.
Cummings KC III, Napierkowski DE, Parra-Sanchez I, Kurz A, Dalton JE, Brems JJ, et al. Effect of dexamethasone on duration of interscalene nerve blocks with ropivacaine or bupivacaine. Br J Anaesth. 2011;107:446–53.PubMed
7.
Liu J, Richman KA, Grodofsky SR, Bhatt S, Huffman GR, Kelly JD 4th, et al. Is there a dose response of dexamethasone as adjuvant for supraclavicular brachial plexus nerve block? A prospective randomized double-blinded clinical study. J Clin Anesth. 2015;27(3):237–42.PubMed
8.
Tandoc MN, Fan L, Kolesnikov S, Kruglov A, Nader ND. Adjuvant dexamethasone with bupivacaine prolongs the duration of interscalene block: a prospective randomized trial. J Anesth. 2011;25(5):704–9.PubMed
9.
De Oliveira GS Jr, Almeida MD, Benzon HT, et al. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2011;115:575–88.PubMed
10.
Desmet M, Braems H, Reynvoet M, Plasschaert S, van Cauwelaert J, Pottel H, et al. I.V. and perineural dexamethasone are equivalent in increasing the analgesic duration of a single-shot interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo-controlled study. Br J Anaesth. 2013;111:445–52.PubMed
11.
Marty P, Rontes O, Chassery C, Delbos A, et al. Perineural versus systemic dexamethasone in front-foot surgery under ankle block. Reg Anesth Pain Med. 2018;43(7):732–7.PubMed
12.
Attardi B, Takimoto K, Gealy R, et al. Glucocorticoid induced up-regulation of a pituitary K+ channel mRNA in vitro and in vivo. Recept Channels. 1993;1:287–93.PubMed
13.
Williams BA, Hough KA, Tsui BYK, Ibinson JW, Gold MS, Gebhart GF. Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine. Reg Anesth Pain Med. 2012;36(3):225–30.
14.
Ma R, Wang X, Lu C. Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine-serine protein kinase B-dependent mechanism. Neuroscience. 2010;167(2):329–42.PubMed
15.
Hans P, Vanthuyne A. Dewandre PY eta al. Blood glucose concentration profile after 10 mg dexamethasone in non-diabetic and type 2 diabetic patients undergoing abdominal surgery. Br J Anaesth. 2006;97:164–70.PubMed
16.
Ammar AS, Mahmoud KM. Effect of adding dexamethasone to bupivacaine on transverse abdominis plane block for abdominal hysterectomy. A prospective randomized controlled trial. Saudi J Anaesth. 2012;6(3):229–33.PubMedPubMedCentral
17.
Sakae TM, Marchioro P, Trevisol FS, Trevisol DJ. Dexamethasone as a ropivacaine adjuvant for ultrasound-guided interscalene brachial plexus block: a randomized, double-blinded clinical trial. J Clin Anesth. 2017;38:133–6.PubMed
18.
Jadon A, Panigrahi MR, Parida SS, Chakraborty S, Agrawal PS, Panda A. Buprenorphine improves the efficacy of bupivacaine in nerve plexus block: a double blind randomized evaluation in subclavian perivascular brachial block. J Anaesthesiol Clin Pharmacol. 2009;25(2):207–10.
19.
Behr A, Freo U, Ori C, Westermann B, Alemanno F. Buprenorphine added to levobupivacaine enhances postoperative analgesia of middle interscalene brachial plexus block. J Anesth. 2010;26(5):746–51.
20.
Candido KD, Winnie AP, Ghaleb AH, Fattouh MW, Franco CD. Buprenorphine added to the local anesthetic for axillary brachial plexus block prolongs postoperative analgesia. Reg Anesth Pain Med. 2002;27(2):162–7.PubMed
21.
Candido KD, Hennes J, Gonzalez S. Buprenorphine enhances and prolongs the postoperative analgesic effect of bupivacaine in patients receiving infragluteal sciatic nerve block. Anesthesiology. 2010;113(6):1419–26.PubMed
22.
Leffler A, Frank G, Kistner K, Nau C, et al. Local anesthetic like inhibition of voltage gated Na+ channels by partial μ-opioid receptor agonist buprenorphine. Anesthesiology. 2012;116:1335–46.PubMed
23.
Fournier R, Faust A, Chassot O, Gamulin Z. Perineural clonidine does not prolong levobupivacaine 0.5% after sciatic nerve block using the Labat approach in foot and ankle surgery. Reg Anesth Pain Med. 2012;37(5):521–4.PubMed
24.
Kohli S, Kaur M, Sahoo S, Vajifdar H, Kohli P. Brachial plexus block: comparison of two different doses of clonidine added to bupivacaine. J Anaesthesiol Clin Pharmacol. 2013;29(4):491–5.PubMedPubMedCentral
25.
Couture DJ, Cuniff HM, Maye JP, Pellegrini J. The addition of clonidine to bupivacaine in combined femoral-sciatic nerve block for anterior cruciate ligament reconstruction. AANA J. 2004;72(4):273–8.PubMed
26.
Ilfeld BM, Morey TE, Thannikary LJ, Wright TW, Enneking FK. Clonidine added to continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: a randomized, double-blind, controlled study. Anesth Analg. 2005;100(4):1172–8.PubMed
27.
Popping DM, Elia N, Marret E, Wenk M, Tramer MR. Clonidine as an adjuvant to local anesthetic for peripheral nerve and plexus blocks: a met-analysis of randomized trials. Anesthesiology. 2009;111(2):406–15.PubMed
28.
Kroin JS, Buvnendran A, Beck D, et al. Clonidine prolongation of lidocaine analgesia after sciatic nerve block in rats is mediated via the hyperpolarization-activated cation current, not by α-adrenoreceptors. Anesthesiology. 2004;101:488–94.PubMed
29.
Madan R, Bharti N, Shende D, Khokhar SK, Kaul HL. A dose response study of clonidine with local anesthetic mixture for peribulbar block: a comparison of three doses. Anesth Analg. 2001;93:1593–7.PubMed
30.
Keniya V, Ladi L, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anesthetic requirement. Indian J Anaesth. 2011;55:352–7.PubMedPubMedCentral
31.
•• Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: a systemic review and meta-analysis. Br J Anaesth. 2013;110(6):915–25. This quantitative review examines whether perineural dexmedetomidine as a local anesthetic (LA) adjuvant for neuraxial and peripheral nerve blocks can prolong the duration of analgesia compared with LA alone. PubMed
32.
Rancourt MP, Albert N, Cote M, et al. Posterior tibial nerve sensory blockade duration prolonged by adding dexmedetomidine to ropivacaine. Anesth Analg. 2012;115:958–62.PubMed
33.
Fritsch G, Danninger T, Felder TK, et al. Dexmedetomidine added to ropivacaine extends the duration of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone: a sdingle-center, prospective, triple-blind, randomized controlled trial. Reg Anesth Pain Med. 2014;39(1):37–47.PubMed
34.
Swami SS, Keniya VM, Ladi SD, Rao R. Comparison of dexmedetomidine and clonidine (alpha2 agonist drugs) as an adjuvant to local anaesthesia in supraclavicular brachial plexus block: a randomized double-blind prospective study. Indian J Anaesth. 2012;56(3):243–9.PubMedPubMedCentral
35.
Huang Y, Lu Y, Zhang L, Yan J, Jiang J, Jiang H. Perineural dexmedetomidine attenuates inflammation in rat sciatic nerve via the NF-kappaB pathway. Int J Mol Sci. 2014;15:4049–59.PubMedPubMedCentral
36.
Tufek A, Kaya S, Tokgoz O, Firat U, Evliyaoglu O, Celik F, et al. The protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve inflammation is mediated by mast cells. Clin Invest Med. 2013;36:E95–102.PubMed
37.
Dowdy EG, Kaya K, Gocho Y. Some pharmacologic similarities of ketamine, lidocaine, and procaine. Anesth Analg. 1973;52:839–42.PubMed
38.
Apiliogullari S, Sahin AS, Dolanmaz D, Yildirim G. Assessment of the local effects of ketamine requires exclusion of systemic effects. J Oral Maxillofac Surg. 2009;67(12):2699.PubMed
39.
Lee IO, Kim WK, Kong MH, Lee MK, Kim NS, Choi YS, et al. No enhancement of sensory and motor blockade by ketamine added to ropivacaine interscalene brachial plexus blockade. Acta Anaesthesiol Scand. 2002;46(7):821–6.PubMed
40.
Albert J, Lofstrom B. Bilateral ulnar nerve blocks of the evaluation of local anesthetic agents. Tests with a new agent, prilocaine, and with lidocaine in solution with and without epinephrine. Acta Anaesthesiol Scand. 1965;9:203–11.PubMed
41.
Song JH, Shim HY, Lee TJ, Jung JK, Cha YD, Lee DI, et al. Comparison of dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in brachial plexus block. Korean J Anaesthesiol. 2014;66(4):283–9.
42.
Weber A, Fournier R, Van Gessel E, et al. Epinephrine does not prolong the analgesia of 20 ml ropivacaine 0.5% or 0.2% in a femoral three-in-one block. Anesth Analg. 2001;93:1327–31.PubMed
43.
Dogru K, Duygulu F, Yildiz K, Boyaci A, et al. Hemodynamic and blockade effects of high/low epinephrine doses during axillary brachial plexus blockade with lidocaine 1.5%: a randomized, double-blinded study. Reg Anesth Pain Med. 2003;28(5):401–5.PubMed
44.
Myers RR, Heckman HM. Effects of local anesthesia on nerve blood flow: studies using lidocaine with and without epinephrine. Anesthesiology. 1989;71(5):757–62.PubMed
45.
Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous system: neurotoxicity and neural blood flow. Reg Anesth Pain Med. 2003;28(2):124–34.PubMed
46.
Arcioni R, Palpisani S, Tigano S, et al. Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements: a prospective, randomized, double-blind, controlled trial in patient undergoing major orthopedic surgery. Acta Anesthesiol Scand. 2007;51:482–9.
47.
Vastani N, Seifert B, Spahn DR, Maurer K. Sensitivities of rat primary sensory afferent neres to magnesium: implications for differential nerve blocks. Eur J Anaesthesiol. 2013;30(1):21–8.PubMed
48.
Lee AR, Yi H, Chung IS. Magnesium added to bupivacaine prolongs the duration of analgesia after interscalene nerve block. Can J Anaesth. 2012;59(1):21–7.PubMed
49.
Gunduz A, Bilir A, Gulec S. Magnesium added to prilocaine prolongs the duration of axillary block. Reg Anesth Pain Med. 2006;31(3):233–6.PubMed
50.
Ekmekci P, Bengisun ZK, Akan B, Kazbek BK, Ozkan KS, Suer AH. The effect of magnesium added to levobupivacaine for femoral nerve block on postoperative analgesia in patients undergoing ACL reconstruction. Knee Surg Sports Traumatol Arthrosc. 2013;21(5):1119–24.PubMed
51.
Saeki H, Matsumoto M, Kaneko S, Tsuruta S, Cui YJ, Ohtake K, et al. Is intrathecal magnesium sulfate safe and protective against ischemic spinal cord injury in rabbits? Anesth Analg. 2004;99(6):1805–12.PubMed
52.
James MF. Clinical use of magnesium infusions in anesthesia. Anesth Analg. 1992;74:129–37.PubMed
53.
Edwards M, Serrao JM, Gent JP, Goodchild CS. On the mechanism by which midazolam causes spinally mediated analgesia. Anesthesiology. 1990;73:273–7.PubMed
54.
Jarbo K, Batra YK, Pando NB. Brachial plexus block with midazolam and bupivacaine improves analgesia. Can J Anaesth. 2005;52:822–6.PubMed
55.
Haeseler G, Foadi N, Ahrens J, Dengler R, Hecker H, Leuwer M. Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Pain. 2006;126:234–44.PubMed
56.
Alemanno F, Ghisi D, Fanelli A, et al. Tramadol and 0.5% levobupivacaine for single-shot interscalene block: effects on postoperative analgesia in patients undergoing shoulder arthroplasty. Minerva Anestesiol. 2012;78:291–6.PubMed
57.
Kemisci E, Izdes S, Gozdemir M, et al. Tramadol does not prolong the effect of ropivacaine 7.5 mg/ml for axillary brachial plexus block. Act Anesthesiol Scand. 2007;51:736–41.
58.
Van Elstraete AC, Pastureau F, Lebrun T, Mehdaoui H. Neostigmine added to lidocaine axillary nerve block for postoperative analgesia. Eur J Anaesthesiol. 2001;18(4):257–60.PubMed
59.
Bouaziz H, Paqueron X, Bur ML, Merle M, Laxenaire MC, Benhamou D. No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus block. Anesthesiology. 1999;91(1):78–83.PubMed
60.
•• YaDeau JT, Paroli L, Fields KG, Kahn RL, LaSala VR, Jules-Elysee KM, et al. Addition of dexamethasone and buprenorphine to bupivacaine sciatic nerve block. Reg Anesth Pain Med. 2015;40:321–9. This randomized study investigated the effect of combination of perineural additives dexamethasone and buprenorphine on pain scores, block duration, and opioid use after foot and ankle surgery. PubMedPubMedCentral
61.
YaDeau JT, Gordon MA, Lin Y, Craig EV, et al. Buprenorphine, clonidine, dexamethasone and ropivacaine for interscalene nerve blockade: a prospective, randomized, blinded, ropivacaine dose-response study. Pain Med. 2016;17(5):940–60.PubMed
62.
•• Turner JD, Dobson SW, Henshaw DS, Edwards CJ, Weller RS, Reynolds JW, et al. Single-injection adductor canal block with multiple adjuvants provides equivalent analgesia when compared with continuous adductor canal blockade for primary total knee arthroplasty: a double-blinded, randomized, controlled, equivalency trial. J Arthroplast. 2018;33:3160–6. This randomized controlled study compared a single injection of local anesthetic bupivacaine adductor canal block with adjuvants clonidine, dexamethasone, buprenorphine, and epinephrine to continuous adductor canal block.
63.
Buvanendran A, Kroin JS, Li J, Moric M, Tuman KJ. Relative contribution of adjuvants to local anesthetic for prolonging the duration of peripheral nerve blocks in rats. Reg Anesth Pain Med. 2016;41(5):589–92.PubMed
64.
•• Marhofer P, Columb M, Hopkins PM, et al. Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised, triple-blinded crossover study in volunteers. Br J Anaesth. 2019; (Article in press). This randomized cross-over study in volunteers has suggested uncertainty about the efficacy of dexamethasone on the duration of peripheral nerve blockade.
Metadata
Title
Local Anesthetic Additives for Regional Anesthesia: a Review of Current Literature and Clinical Application
Authors
Promil Kukreja
Lisa MacBeth
Joel Feinstein
Publication date
01-09-2019
Publisher
Springer US
Published in
Current Anesthesiology Reports / Issue 3/2019
Electronic ISSN: 2167-6275
DOI
https://doi.org/10.1007/s40140-019-00334-z

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