Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

Meghan A Kirksey, Stephen C Haskins, Jennifer Cheng, Spencer S Liu, Meghan A Kirksey, Stephen C Haskins, Jennifer Cheng, Spencer S Liu

Abstract

Background: The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants.

Objectives: To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks.

Methods: Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded.

Results: Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks.

Conclusions: Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. PRISMA flowchart.
Fig 1. PRISMA flowchart.
Details regarding records that were identified, screened, and assessed for eligibility are provided, according to the PRISMA guidelines.
Fig 2. Modified Jadad Scale.
Fig 2. Modified Jadad Scale.
Scoring guidelines for the modified Jadad scale, which was used to assess each study, are shown.

References

    1. Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011;113(4):904–25. 10.1213/ANE.0b013e3182285e01
    1. Williams BA, Hough KA, Tsui BY, 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(3):225–30. 10.1097/AAP.0b013e3182176f70
    1. Williams BA, Murinson BB, Grable BR, Orebaugh SL. Future considerations for pharmacologic adjuvants in single-injection peripheral nerve blocks for patients with diabetes mellitus. Reg Anesth Pain Med. 2009;34(5):445–57. 10.1097/AAP.0b013e3181ac9e42
    1. Williams BA, Schott NJ, Mangione MP, Ibinson JW. Perineural dexamethasone and multimodal perineural analgesia: how much is too much? Anesth Analg. 2014;118(5):912–4. 10.1213/ANE.0000000000000203
    1. Williams BA, Butt MT, Zeller JR, Coffee S, Pippi MA. Multimodal perineural analgesia with combined bupivacaine-clonidine-buprenorphine-dexamethasone: safe in vivo and chemically compatible in solution. Pain Med. 2015;16(1):186–98. 10.1111/pme.12592
    1. Williams BA, Ibinson JW, Mangione MP, Modrak RT, Tonarelli EJ, Rakesh H, et al. Research priorities regarding multimodal peripheral nerve blocks for postoperative analgesia and anesthesia based on hospital quality data extracted from over 1,300 cases (2011–2014). Pain Med. 2015;16(1):7–12. 10.1111/pme.12609
    1. Williams BA, Ibinson JW, Mangione MP, Scanlan RL, Cohen PZ. Clinical benchmarks regarding multimodal peripheral nerve blocks for postoperative analgesia: observations regarding combined perineural midazolam-clonidine-buprenorphine-dexamethasone. Pain Med. 2015;16(1):1–6. 10.1111/pme.12599
    1. Neal JM, Brull R, Chan VW, Grant SA, Horn JL, Liu SS, et al. The ASRA evidence-based medicine assessment of ultrasound-guided regional anesthesia and pain medicine: Executive summary. Reg Anesth Pain Med. 2010;35(2 Suppl):S1–9. 10.1097/AAP.0b013e3181d22fe0
    1. West S, King V, Carey TS, Lohr KN, McKoy N, Sutton SF, et al. Systems to rate the strength of scientific evidence (Prepared by Research Triangle Institute-University of North Carolina Evidence-based Practice Center under contract No. 290-97-0011). Research Triangle Institute-University of North Carolina Evidence-based Practice C, United States. Agency for Healthcare R, Quality, editors. Rockville, MD: Agency for Healthcare Research and Quality; 2002.
    1. Oxford Centre for Evidence-based Medicine-Levels of Evidence (March 2009) [cited 2015 February 11]. Available from: .
    1. Picard PR, Tramer MR, McQuay HJ, Moore RA. Analgesic efficacy of peripheral opioids (all except intra-articular): a qualitative systematic review of randomised controlled trials. Pain. 1997;72(3):309–18.
    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 mu-opioid receptor agonist buprenorphine. Anesthesiology. 2012;116(6):1335–46. 10.1097/ALN.0b013e3182557917
    1. Koppert W, Ihmsen H, Korber 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(1–2):15–22.
    1. Troster A, Ihmsen H, Singler B, Filitz J, Koppert W. Interaction of fentanyl and buprenorphine in an experimental model of pain and central sensitization in human volunteers. Clin J Pain. 2012;28(8):705–11. 10.1097/AJP.0b013e318241d948
    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(9):858–62.
    1. Candido KD, Franco CD, Khan MA, Winnie AP, Raja DS. Buprenorphine added to the local anesthetic for brachial plexus block to provide postoperative analgesia in outpatients. Reg Anesth Pain Med. 2001;26(4):352–6.
    1. 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.
    1. Candido KD, Hennes J, Gonzalez S, Mikat-Stevens M, Pinzur M, Vasic V, et al. Buprenorphine enhances and prolongs the postoperative analgesic effect of bupivacaine in patients receiving infragluteal sciatic nerve block. Anesthesiology. 2010;113(6):1419–26. 10.1097/ALN.0b013e3181f90ce8
    1. 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. 2012;26(5):746–51. 10.1007/s00540-012-1416-4
    1. 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.
    1. Skledar SJ, Williams BA, Vallejo MC, Dalby PL, Waters JH, Glick R, et al. Eliminating postoperative nausea and vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable? ScientificWorldJournal. 2007;7:959–77.
    1. Williams BA, Kentor ML, Skledar SJ, Orebaugh SL, Vallejo MC. Routine multimodal antiemesis including low-dose perphenazine in an ambulatory surgery unit of a university hospital: a 10-year history. Supplement to: Eliminating postoperative nausea and vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable? ScientificWorldJournal. 2007;7:978–86.
    1. Henao JP, Peperzak KA, Lichvar AB, Orebaugh SL, Skledar SJ, Pippi MA, et al. Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg: an 11-year retrospective analysis. Eur J Anaesthesiol. 2014;31(4):231–5. 10.1097/EJA.0000000000000048
    1. Bourke DL, Furman WR. Improved postoperative analgesia with morphine added to axillary block solution. J Clin Anesth. 1993;5(2):114–7.
    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(1):23–6.
    1. Sternlo JE, Hagerdal M. Perineuronal morphine in intercostal block. Anaesthesia. 1992;47(7):613–5.
    1. Racz H, Gunning K, Della Santa D, Forster A. Evaluation of the effect of perineuronal morphine on the quality of postoperative analgesia after axillary plexus block: a randomized double-blind study. Anesth Analg. 1991;72(6):769–72.
    1. Keskinbora K, Aydinli I. Perineural morphine in patients with chronic ischemic lower extremity pain: Efficacy and long-term results. J Anesth. 2009;23(1):11–8. 10.1007/s00540-008-0700-9
    1. Nishikawa K, Kanaya N, Nakayama M, Igarashi M, Tsunoda K, Namiki A. Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism. Anesth Analg. 2000;91(2):384–7.
    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(5):590–4.
    1. Fletcher D, Kuhlman G, Samii K. Addition of fentanyl to 1.5% lidocaine does not increase the success of axillary plexus block. Reg Anesth. 1994;19(3):183–8.
    1. Kardash K, Schools A, Concepcion M. Effects of brachial plexus fentanyl on supraclavicular block. A randomized, double-blind study. Reg Anesth. 1995;20(4):311–5.
    1. Magistris L, Casati A, Albertin A, Deni F, Danelli G, Borghi B, et al. Combined sciatic-femoral nerve block with 0.75% ropivacaine: effects of adding a systemically inactive dose of fentanyl. Eur J Anaesthesiol. 2000;17(6):348–53.
    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. 2010;18(4):298–302.
    1. Karakaya D, Buyukgoz F, Baris S, Guldogus F, Tur A. Addition of fentanyl to bupivacaine prolongs anesthesia and analgesia in axillary brachial plexus block. Reg Anesth Pain Med. 2001;26(5):434–8.
    1. Sert H, Muslu B, Usta B, Colak N, Irem Demircioglu R, Gozdemir M. A comparison of articaine and fentanyl-supplemented articaine for hemodialysis fistula creation under ultrasound-guided axillary block. Ren Fail. 2011;33(3):280–4. 10.3109/0886022X.2011.560502
    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(1):34–9. 10.4103/0019-5049.93341
    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(1):234–7. 10.1213/ANE.0b013e3181e1e9ab
    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(4):899–920.
    1. Werdehausen R, Braun S, Hermanns H, Kremer D, Kury 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(5):436–43. 10.1097/AAP.0b013e318226ba62
    1. Braun H. Ueber die bedeutung des ephinephrine fur die chirurgie. Munch Med Wschr. 1903;50:352–3.
    1. Dogru K, Duygulu F, Yildiz K, Kotanoglu MS, Madenoglu H, Boyaci A. 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.
    1. 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 Anesthesiol. 2014;66(4):283–9. 10.4097/kjae.2014.66.4.283
    1. Weber A, Fournier R, Van Gessel E, Riand N, Gamulin Z. 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(5):1327–31.
    1. Eledjam JJ, Deschodt J, Viel EJ, Lubrano JF, Charavel P, d'Athis F, et al. Brachial plexus block with bupivacaine: effects of added alpha-adrenergic agonists: comparison between clonidine and epinephrine. Can J Anaesth. 1991;38(7):870–5.
    1. 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.
    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(4):343–50.
    1. Neal JM. Effects of epinephrine in local anesthetics on the central and peripheral nervous systems: Neurotoxicity and neural blood flow. Reg Anesth Pain Med. 2003;28(2):124–34.
    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(2):488–94.
    1. Tamsen A, Gordh T. Epidural clonidine produces analgesia. Lancet. 1984;2(8396):231–2.
    1. Popping DM, Elia N, Marret E, Wenk M, Tramer MR. Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials. Anesthesiology. 2009;111(2):406–15. 10.1097/ALN.0b013e3181aae897
    1. McCartney CJ, 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(4):330–8.
    1. YaDeau JT, LaSala VR, Paroli L, Kahn RL, Jules-Elysee KM, Levine DS, et al. Clonidine and analgesic duration after popliteal fossa nerve blockade: randomized, double-blind, placebo-controlled study. Anesth Analg. 2008;106(6):1916–20. 10.1213/ane.0b013e318172fe44
    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(5):521–4. 10.1097/AAP.0b013e3182606168
    1. Jaiswal R, Bansal T, Mehta S, Ahlawat G. A study to evaluate the effect of adding Clonidine to Ropivacaine for axillary plexus blockade. Asian J Pharm Clin Res. 2013;6(SUPPL.3):165–8.
    1. 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. 10.4103/0970-9185.119147
    1. Chakraborty S, Chakrabarti J, Mandal MC, Hazra A, Das S. Effect of clonidine as adjuvant in bupivacaine-induced supraclavicular brachial plexus block: A randomized controlled trial. Indian J Pharmacol. 2010;42(2):74–7. 10.4103/0253-7613.64498
    1. Molnar RR, Davies MJ, Scott DA, Silbert BS, Mooney PH. Comparison of clonidine and epinephrine in lidocaine for cervical plexus block. Reg Anesth. 1997;22(2):137–42.
    1. Trivedi V, Patel N. A comparative clinical study of injection clonidine versus midazolam in supraclavicular brachial plexus block for sedation and postoperative analgesia: a study of 60 cases. J Indian Med Assoc. 2010;108(9):563–7.
    1. Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology. 2000;93(5):1345–9.
    1. Brummett CM, Hong EK, Janda AM, Amodeo FS, Lydic R. Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current. Anesthesiology. 2011;115(4):836–43. 10.1097/ALN.0b013e318221fcc9
    1. Memis D, Turan A, Karamanlioglu B, Pamukcu Z, Kurt I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg. 2004;98(3):835–40, table of contents.
    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(6):915–25. 10.1093/bja/aet066
    1. Agarwal S, Aggarwal R, Gupta P. Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block. J Anaesthesiol Clin Pharmacol. 2014;30(1):36–40. 10.4103/0970-9185.125701
    1. 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(1):37–47. 10.1097/AAP.0000000000000033
    1. Lin YN, Li Q, Yang RM, Mao ZX, Liu JC. Addition of dexmedetomidine to ropivacaine improves cervical plexus block. Acta Anaesthesiol Taiwan. 2013;51(2):63–6. 10.1016/j.aat.2013.06.001
    1. Marhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a volunteer study. Br J Anaesth. 2013;110(3):438–42. 10.1093/bja/aes400
    1. 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(4):958–62.
    1. 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 randomised double-blind prospective study. Indian J Anaesth. 2012;56(3):243–9. 10.4103/0019-5049.98767
    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(2):e55556 10.1371/journal.pone.0055556
    1. 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(2):E95–102.
    1. Choi S, Rodseth R, McCartney CJ. 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(3):427–39. 10.1093/bja/aet417
    1. Biradar PA, Kaimar P, Gopalakrishna K. Effect of dexamethasone added to lidocaine in supraclavicular brachial plexus block: A prospective, randomised, double-blind study. Indian J Anaesth. 2013;57(2):180–4. 10.4103/0019-5049.111850
    1. Ammar AS, Mahmoud KM. Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial. Saudi J Anaesth. 2012;6(3):229–33. 10.4103/1658-354X.101213
    1. Rasmussen SB, Saied NN, Bowens C Jr, Mercaldo ND, Schildcrout JS, Malchow RJ. Duration of upper and lower extremity peripheral nerve blockade is prolonged with dexamethasone when added to ropivacaine: a retrospective database analysis. Pain Med. 2013;14(8):1239–47. 10.1111/pme.12150
    1. Saritas A, Sabuncu C. Comparison of clinical effects of prilocaine, dexamethasone added to prilocaine and levobupivacaine on brachial plexus block. J Pak Med Assoc. 2014;64(4):433–6.
    1. Fredrickson MJ, Danesh-Clough TK, White R. Adjuvant dexamethasone for bupivacaine sciatic and ankle blocks: results from 2 randomized placebo-controlled trials. Reg Anesth Pain Med. 2013;38(4):300–7. 10.1097/AAP.0b013e318292c121
    1. 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(3):445–52. 10.1093/bja/aet109
    1. Rahangdale R, Kendall MC, McCarthy RJ, Tureanu L, Doty R Jr, Weingart A, et al. The effects of perineural versus intravenous dexamethasone on sciatic nerve blockade outcomes: a randomized, double-blind, placebo-controlled study. Anesth Analg. 2014;118(5):1113–9. 10.1213/ANE.0000000000000137
    1. Sondekoppam RV, Uppal V, Ganapathy S. Intravenous or perineural dexamethasone for interscalene brachial plexus block: the equivalence not yet proven. Br J Anaesth. 2014;112(1):175–6.
    1. 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. 10.1016/j.jclinane.2014.12.004
    1. Ma R, Wang X, Lu C, Li C, Cheng Y, Ding G, et al. Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine-serine protein kinase B-dependent mechanism. Neuroscience. 2010;167(2):329–42. 10.1016/j.neuroscience.2009.12.049
    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(4):325–33.
    1. Kim YH, Lee PB, Park J, Lim YJ, Kim YC, Lee SC, et al. The neurological safety of epidural parecoxib in rats. Neurotoxicology. 2011;32(6):864–70. 10.1016/j.neuro.2011.05.011
    1. Canduz B, Aktug H, Mavioglu O, Erkin Y, Yilmaz O, Uyanikgil Y, et al. Epidural lornoxicam administration—innocent. J Clin Neurosci. 2007;14(10):968–74.
    1. Guven M, Mert T, Gunay I. Effects of tramadol on nerve action potentials in rat: comparisons with benzocaine and lidocaine. Int J Neurosci. 2005;115(3):339–49.
    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(2):147–52.
    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(5):373–85. 10.2146/ajhp130336
    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(3):291–6.
    1. Kaabachi O, Ouezini R, Koubaa W, Ghrab B, Zargouni A, Ben Abdelaziz A. Tramadol as an adjuvant to lidocaine for axillary brachial plexus block. Anesth Analg. 2009;108(1):367–70. 10.1213/ane.0b013e31818e0c6b
    1. Sarsu S, Mizrak A, Karakurum G. Tramadol use for axillary brachial plexus blockade. J Surg Res. 2011;165(1):e23–7. 10.1016/j.jss.2010.09.032
    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(3):352–6.
    1. Robaux S, Blunt C, Viel E, Cuvillon P, Nouguier P, Dautel G, et al. Tramadol added to 1.5% mepivacaine for axillary brachial plexus block improves postoperative analgesia dose-dependently. Anesth Analg. 2004;98(4):1172–7, table of contents.
    1. Kapral S, Gollmann G, Waltl B, Likar R, Sladen RN, Weinstabl C, et al. Tramadol added to mepivacaine prolongs the duration of an axillary brachial plexus blockade. Anesth Analg. 1999;88(4):853–6.
    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(6):736–41.
    1. Omar AM, Mansour MA, Abdelwahab HH, Aboushanab OH. Role of ketamine and tramadol as adjuncts to bupivacaine 0.5% in paravertebral block for breast surgery: A randomized double-blind study. Egypt J Anaesth. 2011;27(2):101–5.
    1. Nishiyama T, Matsukawa T, Hanaoka K. Continuous epidural administration of midazolam and bupivacaine for postoperative analgesia. Acta Anaesthesiol Scand. 1999;43(5):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(1):91–7.
    1. Erdine S, Yucel A, Ozyalcin S, Ozyuvaci E, Talu GK, Ahiskali B, et al. Neurotoxicity of midazolam in the rabbit. Pain. 1999;80(1–2):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(2):218–23.
    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(1):21–8. 10.1097/EJA.0b013e32835949ab
    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(2):169–73.
    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. 2012;59(1):21–7. 10.1007/s12630-011-9604-5
    1. Gunduz A, Bilir A, Gulec S. Magnesium added to prilocaine prolongs the duration of axillary plexus block. Reg Anesth Pain Med. 2006;31(3):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(10):607–9.
    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(6):1805–12, table of contents.
    1. Albrecht E, Kirkham KR, Liu SS, Brull R. The analgesic efficacy and safety of neuraxial magnesium sulphate: a quantitative review. Anaesthesia. 2013;68(2):190–202. 10.1111/j.1365-2044.2012.07337.x
    1. Weber WV, Jawalekar KS, Jawalekar SR. The effect of ketamine on nerve conduction in isolated sciatic nerves of the toad. Neurosci Lett. 1975;1(2):115–20.
    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(7):821–6.
    1. Borgbjerg FM, Svensson BA, Frigast C, Gordh T Jr. Histopathology after repeated intrathecal injections of preservative-free ketamine in the rabbit: a light and electron microscopic examination. Anesth Analg. 1994;79(1):105–11.
    1. An K, Elkassabany NM, Liu J. Dexamethasone as adjuvant to bupivacaine prolongs the duration of thermal antinociception and prevents bupivacaine-induced rebound hyperalgesia via regional mechanism in a mouse sciatic nerve block model. PLoS One. 2015;10(4):e0123459 10.1371/journal.pone.0123459

Source: PubMed

3
Subskrybuj