Potential neurotoxic effect of dexamethasone used as adjuvant to local anesthetics during peripheral nerve blockade

Ilvana Hasanbegovic, Lejla Dervisevic, Amina Valjevac, Suada Hasanovic

Abstract


Background: The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased siginificantly in recent years. Many additives to local anesthetics to prolong the duration of analgesia for peripheral nerve blocks have been studied. Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. The aim of this study is to determine possible toxic effects of dexamethasone on peripheral nerve tissue and the dependence of these effects on the place of intraneural applications.

Methods and Materials: A rat sciatic nerve block model was used.  The study was conducted in accordance with the principles of laboratory animal care and was approved by the Laboratory Animal Care and Use Committee. Fifty adult Wistar rats (300 g) both sexes were studied. After induction of general anesthesia, the sciatic nerve was exposed bilaterally. Sciatic nerves were randomly assigned by the method of sealed envelopes to recive: intraneural, intrafascicular 2 mL of lidocaine with dexamethasone  (n=25), intraneural, extrafascicular injection  2 mL of lidocaine with dexamethasone (n=25),  perineural 2 mL of lidocaine with dexamethasone  (n=25) and perineural 2 mL of saline 0.9%  (n=25). Injection pressure was continuosly recorded using an in-line digital manometer. Increased injection pressure was used to distinguish intrafascicular from extrafascicular inrtaneural injections. After injection, the rats were awakened and subjected to serial neurologic examinations. Neurologic examination protocol was followed to determine proprioception by tactile placement response, motor function by extensor postural thrust and nociception by withdrawal reflex. On day 3 of the experiment, the animals were sacrificed and the neural tissue histologically examined.

Results: Intraneural injections (intrafasciculary and extrafasciculary) of lidocaine in combination with dexamethasone caused neurological deficits and severe pathohistological damage to nerve fibers. All perineural injections (independent of the tested solution), combined with low injection pressure showed a uniform changes, with minimal histological deviation of the normal structure of the nerve fiber.

Conclusions: When applied intraneuraly dexamethasone in combination with lidocaine caused nerve fiber damage. However, future studies are required to elucidate the most effective route and optimum dosing range for dexamethasone’s use in this field.


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References


Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011; 113(4):904–25.

Brummett CM. Williams BA. Additives to Local Anesthetics for Peripheral Nerve Blockade. Int Anesthesiol Clin. 2011 ; 49(4): 104–116.

Moiniche S, Mikkelsen S, Wetterslev J, Dahl JB: A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations. Br J Anaesth 1998; 81: 377–83.

Adnan T, Elif AA, Ayse K, Gulnaz A. Clonidine as an adjuvant for lidocaine in axillary brachial plexus block in patients with chronic renal failure. Acta Anaesthesiol Scand. 2005;49(4):563-8.

Duma A, Urbanek B, Sitzwohl C, Kreiger A, Zimpfer M, Kapral S. Clonidine as an adjuvant to local anaesthetic axillary brachial plexus block: a randomized, controlled study. Br J Anaesth. 2005;94(1):112-6.

Karakaya D, Büyükgöz F, Bariş S, Güldoğuş F, Tür A. Addition of fentanyl to bupivacaine prolongs anesthesia and analgesia in axillary brachial plexus block. Reg Anesth Pain Med. 2001;26(5):434-8.

Fanelli G, Casati A, Magistris L, Berti M, Albertin A, Scarioni M, Torri G. Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine. Acta Anaesthesiol Scand. 2001;45(5):590-4.

Clerc S, Vuilleumier H, Frascarolo P, Spahn DR, Gardaz JP. Is the effect of inguinal field block with 0.5% bupivacaine on postoperative pain after hernia repair enhanced by addition of ketorolac or S(+) ketamine? Clin J Pain. 2005;21(1):101-5.

Noyan A. On effects of ketamine to axillary block in hand surgery. J Reconstr Microsurg. 2002;18(3):197.

Jarbo K, Batra YK, Panda NB. Brachial plexus block with midazolam and bupivacaine improves analgesia. Can J Anaesth. 2005;52(8):822-6.

Colombo G, Padera R, Langer R, Kohane DS. Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone. J Biomed Mater Res A. 2005;75(2):458-64.

Dräger C, Benziger D, Gao F, Berde CB.Prolonged intercostal nerve blockade in sheep using controlled-release of bupivacaine and dexamethasone from polymer microspheres. Anesthesiology. 1998;89(4):969-79.

Castillo J, Curley J, Hotz J, Uezono M, Tigner J, Chasin M, Wilder R, Langer R, Berde C. Glucocorticoids prolong rat sciatic nerve blockade in vivo from bupivacaine microspheres. Anesthesiology. 1996;85(5):1157-66.

Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg. 2006;102:263-7.

Shrestha BR, Maharjan SK, Tabedar S. Supraclavicular brachial plexus block with and without dexamethasone - a comparative study. Kathmandu Univ. 2003;1:158-60.

Parrington SJ, O'Donnell D, Chan VWS, et al. Dexamethasone Added to Mepivacaine Prolongs the Duration of Analgesia After Supraclavicular Brachial Plexus Blockade. Regional Anesthesia and Pain Medicine. 2010;35:422-6.

National Institutes of Health. Principles of Laboratory Animal Care. National Institutes of Health publication No. 86-23. Bethesda, MD: National Intitutes of Health, 1985.

Thalhammer JG. Vladimirova M. Bershadshy B. Strichartz GR. Neurologic evaluation of the rat during sciatic nerve blok with lidocaine. Anesthesiology. 1995; 82: 1013-25.

Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988: 179-214.

Williams BA, Murison BB, Grable BR, Orebaugh SL. Future consideration for pharmacologic adjuvants in single – injection peripheral nerve blocks for patients with diabetes mellitus. Reg Anesth Pain Med. 2009; 34:445-457.

Costantini R, Affaitati G, Fabrizio A, Giamberardino MA. Controlling pain in the postoperative setting. Int J Clin Pharmacol Ther. 2011; 49:116-127.

Whiting DJ, Williams BA, Orebaugh SL, Toshok RR. Case report: postoperative analgesia and preserved motor function with clonidine and buprenorphine via a sciatic perineural catheter. J Clin Anesth. 2009; 21:297-299.

Hogan QH. Pathophysiology of peripheral nerve injury during regional anesthesia. Reg Anesth Pain Med. 2008; 33:435-441.

Brull R, McCartney CJL, Chan VWS, El-Beheiry H. Neurological complications after regional anesthesia: contemporary estimates of risk. Anesth Analg. 2007; 104:965-974.

Hodgson PS, Neal JM, Pollock JE, Liu SS. The Neurotoxicity of Drugs Given Intrathecally (Spinal). Anesthesia & Analgesia. 1999; 88(4):797-809.

Attardi B, Takimoto K, Gealy R, Sevens C, Levitan ES. Glucocorticoid induced up-regulation of a pituitary K+ channel mRNA in vitro and in vivo. Receptors Channel. 1993; 1: 287-93.

Eker HE, Cok OY, Aribogan A, Arsaln G. Management of neuropathic pain with methylprednisolone at the site of nerve injury. Pain Med. 2012; 13: 443-51.

Johansson A, Hao J, Sjolund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand. 1990; 34: 335- 8.

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; 36:225–230.

Kim HJ, Park SH. Median nerve injuries caused by carpal tunnel injections. The Korean journal of pain. 2014; 27: 112–117.

Mackinnon SE, Hudson AR, Gentili F. Peripheral nerve injection injury with steroid agents. Plast Reconstr Surg 1982; 69:482–490.

Williams BA, Neumann KJ, Goel SK, Wu C. Postoperative pain and other acute pain syndromes. In: Benzon HT, Rathmell JP, Wu CL, Turk DC, Argoff CE, editors. Raj’s Practical Management of Pain. 4th ed. Philadelphia, PA: Mosby Elsevier; 2008.

Racz GB, Noe CL. Pelvic spinal neuraxial procedures. In: Raj P, Lou L, Serdar E, et al., editors. Interventional pain management. 2nd ed. Philadelphia, PA: Saunders Elsevier; 2008.

Johannsen A, Dahlin L, Kerns JM. Long term local corticosteroid application does not influence nerve transmission or structure. Acta Anaesthesiol Scand. 1995;39:364–9.

Sapolsky RM. Glucocorticoid Toxicity in the Hippocampus: Reversal by Supplementation with Brain Fuels. Journal of Neuroscience. 1986; 6(8): 2240–2244.

Virgin CE, Ha TP, Packan DR, Tombaugh GC, Yang SH, Horner HC, Sapolsky RM. Glucocorticoids Inhibit Glucose Transport and Glutamate Uptake in Hippocampal Astrocytes: Implication for Glucocorticoid Neurotoxicity. Journal of Neurochemistry. 1991; 57(4): 1422–1428.

Johansson A, Hao J, Sjolund B. Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anaesthesiol Scand 1990; 34: 335–8.

Ke A, Nabil ME, Jiabin L. 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): 1-13.

Kim D, Brown J. Efficacy and safety of lumbar epidural dexamethasone versus methylprednisolone in the treatment of lumbar radiculopathy: a comparison of soluble versus particulate steroids. Clin J Pain. 2011; 27: 518–22.

Neal JM, Rathmell JP, Rowlingson JC. Publishing studies that involve ‘off-label’ use of drugs: formalizing Regional Anesthesia and Pain Medicine’s policy. Reg Anesth Pain Med. 2009; 34: 391–2.

Brummett CM, Williams BA. Additives to local anesthetics for peripheral nerve blockade. Int Anesthesiol Clin. 2011;49(4):104–16.

Pasternak JJ, McGregor DG, Lanier WL. Effect of single-dose dexamethasone on blood glucose concentration in patients undergoing craniotomy. J Neurosurg Anesthesiol. 2004;16:122–5.

Merkler AE, Saini V, Kamel H, et al. Preoperative steroid use and the risk of infectious complications after neurosurgery. Neurohospitalist. 2014;4(2):80–5.

Gentilli F, Hudson A, Hunter D, Kline DG. Peripheral nerve injection injury: An experimental study. Neurosurgery. 1979; 4: 244.

Gentilli F, Hudson A, Hunter D, Kline DG. Nerve injection injury with local anesthetic agents: A light and electronic microscop, fluorescent microscop and horseradish peroxidase study. Neurosurgery. 1980; 6: 263.


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