Review of adjuvants to local anesthetics in peripheral nerve blocks: Current and future trends

G V Krishna Prasad, Sangeeta Khanna, Sharma Vipin Jaishree, G V Krishna Prasad, Sangeeta Khanna, Sharma Vipin Jaishree

Abstract

In recent anesthetic practice, peripheral nerve blocks (PNBs) are used extensively for surgical anesthesia and nonsurgical analgesia. PNBs offer many benefits over other anesthetic techniques in a certain population of patients, and in some specific clinical setting, that may contribute to faster and safer pain relief, increased patient satisfaction, reduced hospital stay, and decreased overall healthcare cost. The technique involves the injection of the anesthetic in the vicinity of a specific nerve or bundle of nerves to block the sensation of pain transmitting to a specific portion of the body. However, the length of analgesia when a single anesthetic is used for PNB may not last long. Therefore, the practice of adding an additional agent called adjuvant has been evolved to prolong the analgesic effect. There are many such adjuvants available that are clinically being used for this purpose imparting great efficacy and safety to the anesthetic process. The adjuvants molecules are generally classified as opioids, alpha-2 agonist, steroids, etc. Most of them are safe to use and show little or no adverse event related to neurotoxicity and tissue damage. Although there is extensive use of such adjuvants in the clinical field, none of the molecules is approved by the FDA and is used as an off-label drug. The risk to benefit ratio must be assessed while using such an agent. This review will try to delineate the basic need of adjuvant in peripheral nerve block and will discuss the advantages and limitations of using different adjuvants and will discuss the future prospect of such application.

Keywords: Additive; alpha-2 agonists; analgesia; opioids; peripheral nerve block; steroid.

Conflict of interest statement

There are no conflicts of interest.

Copyright: © 2020 Saudi Journal of Anesthesia.

References

    1. Chang A, White BA. StatPearls. Treasure Island (FL): StatPearls Publishing; 2019. Peripheral Nerve Blocks.
    1. Chelly JE, Ghisi D, Fanelli A. Continuous peripheral nerve blocks in acute pain management. Br J Anaesth. 2010;105(Suppl 1):i86–96.
    1. Saranteas T, Koliantzaki I, Savvidou O, Tsoumpa M, Eustathiou G, Kontogeorgakos V, et al. Acute pain management in trauma: Anatomy, ultrasound-guided peripheral nerve blocks and special considerations. Minerva Anestesiol. 2019;85:763–73.
    1. Donado C, Solodiuk J, Rangel SJ, Nelson CP, Heeney MM, Mahan ST, et al. Patient- and nurse-controlled analgesia: 22-year experience in a pediatric hospital. Hosp Pediatr. 2019;9:129–33.
    1. Hadzic A. Hadzic's Textbook of Regional Anesthesia and Acute Pain Management. 2nd ed. New York, NY: McGraw-Hill Education; 2017. Pharmacology.
    1. Hussain N, McCartney CJL, Neal JM, Chippor J, Banfield L, Abdallah FW. Local anaesthetic-induced myotoxicity in regional anaesthesia: A systematic review and empirical analysis. Br J Anaesth. 2018;121:822–41.
    1. Opperer M, Gerner P, Memtsoudis SG. Additives to local anesthetics for peripheral nerve blocks or local anesthesia: A review of the literature. Pain Manag. 2015;5:117–28.
    1. Yam M, Loh Y, Tan C, Khadijah Adam S, Abdul Manan N, Basir R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci. 2018;19:2164.
    1. Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases. 2017;5:307.
    1. 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.
    1. Choi S, Rodseth R, McCartney CJL. Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: A systematic review and meta-analysis of randomized trials. Br J Anaesth. 2014;112:427–39.
    1. Kosel J, Bobik P, Tomczyk M. Buprenorphine – The unique opioid adjuvant in regional anesthesia. Expert Rev Clin Pharmacol. 2016;9:375–83.
    1. Karan D, Swaro S, Mahapatra PR, Banerjee A. Effect of dexmedetomidine as an adjuvant to ropivacaine in ilioinguinal-iliohypogastric nerve blocks for inguinal hernia repair in pediatric patients: A randomized, double-blind, control trial. Anesth Essays Res. 2018;12:924–9.
    1. Leffler A, Frank G, Kistner K, Niedermirtl F, Koppert W, Reeh PW, et al. Local anesthetic-like inhibition of voltage-gated Na(+) channels by the partial -opioid receptor agonist buprenorphine. Anesthesiology. 2012;116:1335–46.
    1. Koppert W, Ihmsen H, Körber N, Wehrfritz A, Sittl R, Schmelz M, et al. Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005;118:15–22.
    1. Bazin JE, Massoni C, Bruelle P, Fenies V, Groslier D, Schoeffler P. The addition of opioids to local anaesthetics in brachial plexus block: The comparative effects of morphine, buprenorphine and sufentanil. Anaesthesia. 1997;52:858–62.
    1. Karaman S, Kocabas S, Uyar M, Hayzaran S, Firat V. The effects of sufentanil or morphine added to hyperbaric bupivacaine in spinal anaesthesia for Caesarean section. Eur J Anaesthesiol. 2006;23:285–91.
    1. Axelsson K, Johanzon E, Essving P, Weckstrom J, Ekback G. Postoperative extradural analgesia with morphine and ropivacaine. A double-blind comparison between placebo and ropivacaine 10 mg/h or 16 mg/h. Acta Anaesthesiol Scand. 2005;49:1191–9.
    1. Flory N, Van-Gessel E, Donald F, Hoffmeyer P, Gamulin Z. Does the addition of morphine to brachial plexus block improve analgesia after shoulder surgery? Br J Anaesth. 1995;75:23–6.
    1. Kardash K, Schools A, Concepcion M. Effects of brachial plexus fentanyl on supraclavicular block. A randomized, double-blind study. Reg Anesth. 1995;20:311–5.
    1. Moharari R, Sadeghi J, Khajavi M, Davari M, Mojtahedzadeh M. Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia. Daru J Fac Pharm Tehran Univ Med Sci. 2010;18:298–302.
    1. Fanelli G, Casati A, Magistris L, Berti M, Albertin A, Scarioni M, et al. Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine. Acta Anaesthesiol Scand. 2001;45:590–4.
    1. Bhuvaneswari V, Wig J, Mathew PJ, Singh G. Post-operative pain and analgesic requirements after paravertebral block for mastectomy: A randomized controlled trial of different concentrations of bupivacaine and fentanyl. Indian J Anaesth. 2012;56:34–9.
    1. Sindjelic RP, Vlajkovic GP, Davidovic LB, Markovic DZ, Markovic MD. The addition of fentanyl to local anesthetics affects the quality and duration of cervical plexus block: A randomized, controlled trial. Anesth Analg. 2010;111:234–7.
    1. Kampe S, Weigand C, Kaufmann J, Klimek M, König DP, Lynch J. Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesth Analg. 1999;89:395–8.
    1. Sousa AM, Ashmawi HA, Costa LS, Posso IP, Slullitel A. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models. Braz J Med Biol Res. 2012;45:147–52.
    1. Baraka A, Jabbour S, Ghabash M, Nader A, Khoury G, Sibai A. A comparison of epidural tramadol and epidural morphine for postoperative analgesia. Can J Anaesth. 1993;40:308–13.
    1. Alhashemi JA, Kaki AM. Effect of intrathecal tramadol administration on postoperative pain after transurethral resection of prostate. Br J Anaesth. 2003;91:536–40.
    1. Alemanno F, Ghisi D, Fanelli A, Faliva A, Pergolotti B, Bizzarri F, 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.
    1. Kesimci E, Izdes S, Gozdemir M, Kanbak O. Tramadol does not prolong the effect of ropivacaine 7.5 mg/ml for axillary brachial plexus block. Acta Anaesthesiol Scand. 2007;51:736–41.
    1. Mannion S, O’Callaghan S, Murphy DB, Shorten GD. Tramadol as adjunct to psoas compartment block with levobupivacaine 0.5%: A randomized double-blinded study. Br J Anaesth. 2005;94:352–6.
    1. Eisenach JC, Kock MD, Klimscha W. 2-Adrenergic Agonists for Regional AnesthesiaA Clinical Review of Clonidine (1984 - 1995) Anesthesiol J Am Soc Anesthesiol. 1996;85:655–74.
    1. McCartney CJL, Duggan E, Apatu E. Should we add clonidine to local anesthetic for peripheral nerve blockade. A qualitative systematic review of the literature? Reg Anesth Pain Med. 2007;32:330–8.
    1. Kroin JS, Buvanendran A, Beck DR, Topic JE, Watts DE, Tuman KJ. Clonidine prolongation of lidocaine analgesia after sciatic nerve block in rats Is mediated via the hyperpolarization-activated cation current, not by alpha-adrenoreceptors. Anesthesiology. 2004;101:488–94.
    1. Pöpping DM, Elia N, Marret E, Wenk M, Tramèr MR. Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: A meta-analysis of randomized trials. Anesthesiology. 2009;111:406–15.
    1. YaDeau JT, LaSala VR, Paroli L, Kahn RL, Jules-Elysée KM, Levine DS, et al. Clonidine and analgesic duration after popliteal fossa nerve blockade: Randomized, double-blind, placebo-controlled study. Anesth Analg. 2008;106:1916–20.
    1. 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;37:521–4.
    1. Collins JG, Kitahata LM, Matsumoto M, Homma E, Suzukawa M. Spinally administered epinephrine suppresses noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Anesthesiology. 1984;60:269–75.
    1. Bailard NS, Ortiz J, Flores RA. Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations. Am J Health Syst Pharm. 2014;71:373–85.
    1. Dogru K. 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;28:401–5.
    1. Myers RR, Heckman HM. Effects of local anesthesia on nerve blood flow: Studies using lidocaine with and without epinephrine. Anesthesiology. 1989;71:757–62.
    1. Kroin JS, Buvanendran A, Williams DK, Wagenaar B, Moric M, Tuman KJ, et al. Local anesthetic sciatic nerve block and nerve fiber damage in diabetic rats. Reg Anesth Pain Med. 2010;35:343–50.
    1. Weber A, Fournier R, Van Gessel E, Riand N, Gamulin Z. Epinephrine does not prolong the analgesia of 20 mL ropivacaine 05% or 02% in a femoral three-in-one block. Anesth Analg. 2001:93, 1327.
    1. Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand. 2006;50:222–7.
    1. Abdallah FW, Brull R. Facilitatory effects of perineural dexmedetomidine on neuraxial and peripheral nerve block: A systematic review and meta-analysis. Br J Anaesth. 2013;110:915–25.
    1. Zhang H, Zhou F, Li C, Kong M, Liu H, Zhang P, et al. Molecular mechanisms underlying the analgesic property of intrathecal dexmedetomidine and its neurotoxicity evaluation: An in vivo and in vitro experimental study. PLoS One. 2013;8:e55556.
    1. Attardi B, Takimoto K, Gealy R, Severns C, Levitan ES. Glucocorticoid induced up-regulation of a pituitary K+ channel mRNA in vitro and in vivo. Receptors Channels. 1993;1:287–93.
    1. Parrington SJ, O’Donnell D, Chan VW, Brown-Shreves D, Subramanyam R, Qu M, et al. Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade. Reg Anesth Pain Med. 2010;35:422–6.
    1. Dani C, Vestri V, Bertini G, Pratesi S, Rubaltelli FF. Toxicity of corticosteroids and catecholamines for mice neuronal cell cultures: Role of preservatives. J Matern Fetal Neonatal Med. 2007;20:325–33.
    1. Routray SS, Mishra D, Routray D, Nanda K. Effect of verapamil as an adjuvant to levobupivacaine in supraclavicular brachial plexus block. Anesth Essays Res. 2017;11:656–60.
    1. Routray S, Mishra D, Routray D, Nanda K. Effect of verapamil as an adjuvant to levobupivacaine in supraclavicular brachial plexus block. Anesth Essays Res. 2017;11:656.
    1. Reinhart D. Postoperative analgesia after peripheral nerve block for podiatric surgery: Clinical efficacy and chemical stability of lidocaine alone versus lidocaine plus ketorolac. Reg Anesth Pain Med. 2000;25:506–13.
    1. Mirkheshti A, Saadatniaki A, Salimi A, Manafi Rasi A, Memary E, Yahyaei H. Effects of dexmedetomidine versus ketorolac as local anesthetic adjuvants on the onset and duration of infraclavicular brachial plexus block. Anesthesiol Pain Med. 2014;4:e17620.
    1. Eker HE, Cok OY, Aribogan A, Arslan G. Management of neuropathic pain with methylprednisolone at the site of nerve injury. Pain Med. 2012;13:443–51.
    1. Reeve AJ, Dickenson AH. The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurones in the anaesthetized rat. Br J Pharmacol. 1995;116:2221–8.
    1. Gan TJ, Habib AS. Adenosine as a non-opioid analgesic in the perioperative setting. Anesth Analg. 2007;105:487–94.
    1. Apan A, Basar H, Ozcan S, Buyukkocak U. Combination of adenosine with prilocaine and lignocaine for brachial plexus block does not prolong postoperative analgesia. Anaesth Intensive Care. 2003;31:648–52.
    1. 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;46:821–6.
    1. Nishiyama T, Matsukawa T, Hanaoka K. Continuous epidural administration of midazolam and bupivacaine for postoperative analgesia. Acta Anaesthesiol Scand. 1999;43:568–72.
    1. Malinovsky JM, Cozian A, Lepage JY, Mussini JM, Pinaud M, Souron R. Ketamine and midazolam neurotoxicity in the rabbit. Anesthesiology. 1991;75:91–7.
    1. Erdine S, Yücel A, Ozyalçin S, Ozyuvaci E, Talu GK, Ahiskali B, et al. Neurotoxicity of midazolam in the rabbit. Pain. 1999;80:419–23.
    1. Demirel E, Ugur HC, Dolgun H, Kahilogullari G, Sargon ME, Egemen N, et al. The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits. Anaesth Intensive Care. 2006;34:218–23.
    1. Yaksh TL, Grafe MR, Malkmus S, Rathbun ML, Eisenach JC. Studies on the safety of chronically administered intrathecal neostigmine methylsulfate in rats and dogs. Anesthesiology. 1995;82:412–27.
    1. Werdehausen R, Braun S, Hermanns H, Kremer D, Küry P, Hollmann MW, et al. The influence of adjuvants used in regional anesthesia on lidocaine-induced neurotoxicity in vitro. Reg Anesth Pain Med. 2011;36:436–43.
    1. Lee AR, Yi HW, Chung IS, Ko JS, Ahn HJ, Gwak MS, et al. Magnesium added to bupivacaine prolongs the duration of analgesia after interscalene nerve block. Can J Anaesth J Can Anesth. 2012;59:21–7.
    1. ELShamaa HA, Ibrahim M, Eldesuky Hl. Magnesium sulfate in femoral nerve block, does postoperative analgesia differ? A comparative study. Egypt J Anaesth. 2014;30:169–73.
    1. Gunduz A, Bilir A, Gulec S. Magnesium added to prilocaine prolongs the duration of axillary plexus block. Reg Anesth Pain Med. 2006;31:233–6.
    1. Dogru K, Yildirim D, Ulgey A, Aksu R, Bicer C, Boyaci A. Adding magnesium to levobupivacaine for axillary brachial plexus block in arteriovenous fistule surgery. Bratisl Lek Listy. 2012;113:607–9.
    1. Vastani N, Seifert B, Spahn DR, Maurer K. Sensitivities of rat primary sensory afferent nerves to magnesium: Implications for differential nerve blocks. Eur J Anaesthesiol. 2013;30:21–8.
    1. 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;99:1805–12, table of contents.
    1. Brummett CM, Williams BA. Additives to local anesthetics for peripheral nerve blockade. Int Anesthesiol Clin. 2011;49:104–16.
    1. Capogna G, Celleno D, Laudano D, Giunta F. Alkalinization of local anesthetics Which block, which local anesthetic. Reg Anesth. 1995;20:369–77.
    1. Sabbe MB, Grafe MR, Mjanger E, Tiseo PJ, Hill HF, Yaksh TL. Spinal delivery of sufentanil, alfentanil, and morphine in dogs. Physiologic and toxicologic investigations. Anesthesiology. 1994;81:899–920.
    1. 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. 2011;36:225–30.
    1. Singh S, Bansal P, Dureja J. Off-label use of drugs in regional anesthesia: A need for setting up policies. J Anaesthesiol Clin Pharmacol. 2017;33:448–9.
    1. Korsten HH, Ackerman EW, Grouls RJ, van Zundert AA, Boon WF, Bal F, et al. Long-lasting epidural sensory blockade by n-butyl-p-aminobenzoate in the terminally ill intractable cancer pain patient. Anesthesiology. 1991;75:950–60.
    1. Khan MA, Gerner P, Sudoh Y, Wang GK. Use of a charged lidocaine derivative, tonicaine, for prolonged infiltration anesthesia. Reg Anesth Pain Med. 2002;27:173–9.
    1. MacLeod GF, Wyatt R. Dextran in local anaesthesia. Ann R Coll Surg Engl. 1981;63:60–1.
    1. Tsuchiya M, Mizutani K, Ueda W. Adding dextran to local anesthetic enhances analgesia. J Anesth. 2019;33:163.
    1. Wiles MD, Nathanson MH. Local anaesthetics and adjuvants – Future developments. Anaesthesia. 2010;65:22–37.

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