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Reviews on Recent Clinical Trials

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ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

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Research Article

Intravenous Magnesium – Lidocaine - Ketorolac Cocktail for Postoperative Opioid Resistant Pain: A Case Series of Novel Rescue Therapy

Author(s): Christian Zanza*, Yaroslava Longhitano, Edwin Lin, Jerry Luo, Marco Artico, Benedetta Savarese, Valeria Bonato, Andrea Piccioni, Francesco Franceschi, Samanta Taurone, Ludovico Abenavoli and Jack Marshall Berger

Volume 16, Issue 3, 2021

Published on: 02 December, 2020

Page: [288 - 293] Pages: 6

DOI: 10.2174/1574887115666201202105620

Price: $65

Abstract

Background: Severe postoperative pain is principally managed by opioids. While effective, opioids do not provide adequate relief in many patients and cause many side effects, including antinociceptive tolerance and opioid-induced hyperalgesia. To evaluate if a combination of intravenous Magnesium, Lidocaine, Ketorolac (MLK cocktail) is a useful rescue therapy through synergistic pharmacological mechanisms for acute pain relief. We present the intravenous combination of magnesium, lidocaine, and ketorolac (MLK cocktail) as a possible rescue for opioid insensitive severe post-operative pain.

Materials and Methods: The principal settings were the post-operative care unit (PACU) and the surgical ward. We retrospectively analyzed the electronic medical record and anesthesia documents of 14 patients experiencing severe postoperative pain, >7/10 visual-analogue pain score (VAS), despite receiving at least 8 mg of intravenous morphine milligram equivalents (MME) after arrival in the LAC+USC Medical Center PACU between September 2012 and January 2013. The data reviewed included patients’ demographics, disease etiology, surgical procedure, opioids received perioperatively, and visual-analogue pain scores before and after each analgesic received, and after the MLK cocktail. The a priori primary outcome and a posteriori secondary outcome of this study are mean visual-analogue pain score and morphine milligram equivalent dose administered per hour, respectively. The main tool evaluated has been VAS score.

Results: In patients who failed to respond to opioid analgesics, administration of the MLK cocktail improved the VAS pain scores immediately from 9.4 ± 1.0 to 3.6 ± 3.5. The MLK cocktail also decreased the MME doses/hour in the immediate 12 hours postoperative period from 12.4 ± 5.6 to 1.1 ± 0.9.

Conclusion: In patients experiencing opioid-resistant severe postoperative pain, the magnesium, lidocaine, and ketorolac combination may be an effective nonopioid rescue therapy. Additionally, magnesium, lidocaine, and ketorolac may be utilized in cases complicated by either antinociceptive tolerance or opioid-induced hyperalgesia and can restore opioid responsiveness.

Keywords: Ketorolac, lidocaine, magnesium, multimodal analgesia, opioid antinociceptive tolerance, opioid-induced hyperalgesia, opioid sensitivity, opioid-sparing, severe postoperative pain.

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[1]
Wu CL, Raja SN. Treatment of acute postoperative pain. Lancet 2011; 377(9784): 2215-25.
[http://dx.doi.org/10.1016/S0140-6736(11)60245-6] [PMID: 21704871]
[2]
Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology 2000; 93(4): 1123-33.
[http://dx.doi.org/10.1097/00000542-200010000-00038] [PMID: 11020770]
[3]
Roeckel LA, Le Coz GM, Gavériaux-Ruff C, Simonin F. Opioid-induced hyperalgesia: Cellular and molecular mechanisms. Neuroscience 2016; 338: 160-82.
[http://dx.doi.org/10.1016/j.neuroscience.2016.06.029] [PMID: 27346146]
[4]
American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2012; 116(2): 248-73.
[http://dx.doi.org/10.1097/ALN.0b013e31823c1030] [PMID: 22227789]
[5]
Castro J, Cooney MF. Intravenous Magnesium in the Management of Postoperative Pain. J Perianesth Nurs 2017; 32(1): 72-6.
[http://dx.doi.org/10.1016/j.jopan.2016.11.007] [PMID: 28212916]
[6]
Bujalska-Zadrożny M, Tatarkiewicz J, Kulik K, Filip M, Naruszewicz M. Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades? Eur J Pharm Sci 2017; 99: 113-27.
[http://dx.doi.org/10.1016/j.ejps.2016.11.020] [PMID: 27884758]
[7]
Van Noord B, Berger JM, Motamed A. Opioid resistant pain successfully managed with magnesium, lidocaine, and ketorolac in the post-anesthesia care unit: A case series. J Anesth Clin Res 2012; 3: 3.
[http://dx.doi.org/10.4172/2155-6148.1000196]
[8]
McKay A, Gottschalk A, Ploppa A, Durieux ME, Groves DS. Systemic lidocaine decreased the perioperative opioid analgesic requirements but failed to reduce discharge time after ambulatory surgery. Anesth Analg 2009; 109(6): 1805-8.
[http://dx.doi.org/10.1213/ANE.0b013e3181be371b] [PMID: 19923506]
[9]
Kranke P, Jokinen J, Pace NL, et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev 2015; (7): CD009642
[http://dx.doi.org/10.1002/14651858.CD009642.pub2] [PMID: 26184397]
[10]
White PF, Raeder J, Kehlet H. Ketorolac: its role as part of a multimodal analgesic regimen.Anesth Analg. United States 2012; 114: pp. 250-4.
[http://dx.doi.org/10.1213/ANE.0b013e31823cd524]
[11]
Ng A, Temple A, Smith G, Emembolu J. Early analgesic effects of parecoxib versus ketorolac following laparoscopic sterilization: a randomized controlled trial. Br J Anaesth 2004; 92(6): 846-9.
[http://dx.doi.org/10.1093/bja/aeh161] [PMID: 15121727]
[12]
Weinbroum AA. A single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain. Anesth Analg 2003; 96(3): 789-95.
[http://dx.doi.org/10.1213/01.ANE.0000048088.17761.B4] [PMID: 12598264]
[13]
Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 2011; 14(2): 145-61.
[PMID: 21412369]
[14]
Allouche S, Noble F, Marie N. Opioid receptor desensitization: mechanisms and its link to tolerance. Front Pharmacol 2014; 5: 280.
[http://dx.doi.org/10.3389/fphar.2014.00280] [PMID: 25566076]
[15]
Varrassi G, Fusco M, Skaper SD, et al. A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia: A Review. Pain Ther 2018; 7(1): 59-75.
[http://dx.doi.org/10.1007/s40122-018-0094-9] [PMID: 29594972]
[16]
De Oliveira GS Jr, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 2013; 119(1): 178-90.
[http://dx.doi.org/10.1097/ALN.0b013e318297630d] [PMID: 23669270]
[17]
Sun J, Lin H, He G, Lin W, Yang J. Magnesium sulphate attenuate remifentanil-induced postoperative hyperalgesia via regulating tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord. BMC Anesthesiol 2017; 17(1): 30.
[http://dx.doi.org/10.1186/s12871-017-0325-3] [PMID: 28222697]
[18]
Van Elstraete AC, Sitbon P, Mazoit JX, Conti M, Benhamou D. Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats. Can J Anaesth 2006; 53(12): 1180-5.
[http://dx.doi.org/10.1007/BF03021578] [PMID: 17142651]
[19]
Mert T, Gunes Y, Ozcengiz D, Gunay I. Magnesium modifies fentanyl-induced local antinociception and hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol 2009; 380(5): 415-20.
[http://dx.doi.org/10.1007/s00210-009-0447-3] [PMID: 19697012]
[20]
Weibel S, Jokinen J, Pace NL, et al. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth 2016; 116(6): 770-83.
[http://dx.doi.org/10.1093/bja/aew101] [PMID: 27199310]
[21]
McCarthy GC, Megalla SA, Habib AS. Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery: a systematic review of randomized controlled trials. Drugs 2010; 70(9): 1149-63.
[http://dx.doi.org/10.2165/10898560-000000000-00000] [PMID: 20518581]
[22]
Cui W, Li Y, Li S, et al. Systemic lidocaine inhibits remifentanil-induced hyperalgesia via the inhibition of cPKCgamma membrane translocation in spinal dorsal horn of rats. J Neurosurg Anesthesiol 2009; 21(4): 318-25.
[http://dx.doi.org/10.1097/ANA.0b013e3181abbde5] [PMID: 19955894]
[23]
Cui W, Wang S, Han R, Wang Q, Li J. CaMKII phosphorylation in primary somatosensory cortical neurons is involved in the inhibition of remifentanil-induced hyperalgesia by lidocaine in male sprague-dawley rats. J Neurosurg Anesthesiol 2016; 28(1): 44-50.
[http://dx.doi.org/10.1097/ANA.0000000000000177] [PMID: 25811361]
[24]
Gronwald C, Vegh V, Hollmann MW, Hahnenkamp A, Garaj V, Hahnenkamp K. The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features. Eur J Pharmacol 2012; 674(1): 13-9.
[http://dx.doi.org/10.1016/j.ejphar.2011.10.035] [PMID: 22079424]
[25]
Muth-Selbach U, Hermanns H, Stegmann JU, et al. Antinociceptive effects of systemic lidocaine: involvement of the spinal glycinergic system. Eur J Pharmacol 2009; 613(1-3): 68-73.
[http://dx.doi.org/10.1016/j.ejphar.2009.04.043] [PMID: 19394327]
[26]
Woolf CJ, Ma Q. Nociceptors--noxious stimulus detectors. Neuron 2007; 55(3): 353-64.
[http://dx.doi.org/10.1016/j.neuron.2007.07.016] [PMID: 17678850]
[27]
Cepeda MS, Carr DB, Miranda N, Diaz A, Silva C, Morales O. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Anesthesiology 2005; 103(6): 1225-32.
[http://dx.doi.org/10.1097/00000542-200512000-00018] [PMID: 16306736]
[28]
Lenz H, Raeder J, Draegni T, Heyerdahl F, Schmelz M, Stubhaug A. Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans. Pain 2011; 152(6): 1289-97.
[http://dx.doi.org/10.1016/j.pain.2011.02.007] [PMID: 21396775]
[29]
Ong WY, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol 2018.
[PMID: 29876878]

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