Rev Esp Anestesiol Reanim. 2018;65(5):269---274
Revista Española de Anestesiología y Reanimación www.elsevier.es/redar
REVIEW
Intravenous lidocaine infusion夽,夽夽 G. Soto a,∗ , M. Naranjo González b , F. Calero a a b
Médico Anestesiólogo, Hospital Escuela Eva Perón, Granadero Baigorria, Argentina Médica Anestesióloga, Clínica de Mérida, Mérida, Mexico
Received 2 October 2017; accepted 9 January 2018
KEYWORDS Intravenous lidocaine; Opioid free anaesthesia; Opioid-induced hyperalgesia; Post-operative cognitive dysfunction; Cancer recurrence
PALABRAS CLAVE Lidocaína intravenosa; Anestesia libre de opioides; Hiperalgesia inducida por opioides;
Abstract Systemic lidocaine used in continuous infusion during the peri-operative period has analgesic, anti-hyperalgesic, as well as anti-inflammatory properties. This makes it capable of reducing the use of opioids and inhalational anaesthetics, and the early return of bowel function, and patient hospital stay. The aim of this narrative review was to highlight the pharmacology and indications for clinical application, along with new and interesting research areas. The clinical applications of peri-operative lidocaine infusion have been reviewed in several recent systematic reviews and meta-analyses in patients undergoing open and laparoscopic abdominal procedures, ambulatory procedures, and other types of surgery. Peri-operative lidocaine infusion may be a useful analgesic adjunct in enhanced recovery protocols. Potential benefits of intravenous lidocaine in chronic post-surgical pain, post-operative cognitive dysfunction, and cancer recurrence are under investigation. Due to its immunomodulation properties over surgical stress, current evidence suggests that intravenous lidocaine could be used in the context of multimodal analgesia. © 2018 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.
Perfusión de lidocaína intravenosa Resumen La perfusión perioperatoria de lidocaína intravenosa tiene propiedades analgésicas, antihiperalgésicas y antiinflamatorias, disminuyendo el consumo de opioides y agentes volátiles, brindando una rápida recuperación de la función intestinal y alta hospitalaria. Esta revisión narrativa tiene como objetivo exponer su farmacología e indicaciones para su aplicación en la clínica anestésica. Recientes revisiones sistemáticas y metaanálisis confirman su empleo en cirugía abdominal videolaparoscópica y abierta, como también en otros tipos de cirugía, destacándose su uso en protocolos de pronta recuperación. Potenciales beneficios en dolor crónico posoperatorio, disfunción cognitiva posoperatoria y
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Please cite this article as: Soto G, Naranjo González M, Calero F. Perfusión de lidocaína intravenosa. Rev Esp Anestesiol Reanim. 2018;65:269---274. 夽夽 This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program. An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page: www.elsevier.es/redar ∗ Corresponding author. E-mail address:
[email protected] (G. Soto). 2341-1929/© 2018 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Published by Elsevier Espa˜ na, S.L.U. All rights reserved.
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Disfunción cognitiva posoperatoria; Recurrencia de cáncer
G. Soto et al. recurrencia de cáncer están siendo investigados. La evidencia actual avala su administración en el contexto de analgesia multimodal debido a sus propiedades inmunomoduladoras sobre el estrés quirúrgico, considerándose un fármaco necesario en la clínica perioperatoria moderna. © 2018 Sociedad Espa˜ nola de Anestesiolog´ıa, Reanimaci´ on y Terap´ eutica del Dolor. Publicado por Elsevier Espa˜ na, S.L.U. Todos los derechos reservados.
Introduction Postoperative pain (POP) is a nociceptive stimulus produced by surgery-induced tissue damage, and results in emotional and cognitive experiences. Good pain management reduces morbidity, improves surgical outcomes, and reduces hospital costs. However, estimates suggest that more than 50% of patients undergoing surgical procedures experience moderate to severe pain.1 Persistence of the painful stimulus can even change the plasticity of the nervous system, leading to chronic pain.2 Inter-individual differences in pain thresholds and the use of inappropriate drugs are among the causes of POP. Although opioids are frequently used in pain therapy, they can cause adverse effects, such as respiratory depression, postoperative nausea and vomiting, ileus, urinary retention, hyperalgesia and immune changes.3 Intravenous (iv) perfusion of lidocaine, a drug whose analgesic, antihyperalgesic and anti-inflammatory properties modulate the inflammatory response produced by surgical stress, is an alternative to opioids in pain management.4 Some studies have shown that lidocaine decreases POP and the need for opioids and volatile agents, and rapidly restores intestinal function.5 The antihyperalgesic action of lidocaine reduces allodynia by acting on spinal cord neurons.6 The anti-inflammatory action of the drug, which inhibits cytokine release and polymorphonuclear activation, has been demonstrated in vitro and in vivo.7 The aim of this review is to describe the pharmacology of lidocaine, its indications for use in anaesthesia practice, and its effect on new fields of study, including chronic POP, postoperative cognitive dysfunction (PCD) and cancer recurrence.
Mechanisms of action Lidocaine is an amide-type local anaesthetic that acts by blocking voltage-gated sodium channels (VGSC) in neuronal tissues, thus interrupting synaptic transmission.8 VGSCs are composed of an ␣ subunit (Nav1.5, 260 kDa) and 1 or more  subunits (Nav1.1, Nav1.1 a, Nav3.1; 33---36 kDa). The ␣ subunit is an integral heteromultimeric protein complex consisting of 4 homologous domains (D1---D4), each of which contains 6 ␣-helix transmembrane segments (S1---S6). The C- and N-terminus ends and P loops that bind the domains are intracytoplasmic. The S5---S6 segments and the P loop of each domain form the channel pore that penetrates the membrane. In mammals, VGSCs have 9 different ␣ unit isotypes (Nav1.1 to 1.9), some of which are
associated with neuropathic pain (Nav1.3, 1.7, 1.8 and 1.9) and others with inflammatory pain (Nav1.7, 1.8 and 1.9). Lidocaine passes through the neuron membrane and is converted to its non-ionised form by the effect of pH. It binds to the S6 portion of domain 4 of the ␣ subunit inside the sodium channel. The affinity of lidocaine for VGSCs varies according to the status of the channel, being high when the channel is open and low when it is closed. Therefore, the greater the neural discharge, the greater the number of ionised lidocaine molecules entering the site of action, thus increasing the analgesic capacity of the drug.9 The analgesic effect of intravenous administration is the result of increased acetylcholine levels in the cerebrospinal fluid, which cause downward inhibition, inhibition of glycine receptors, and increase the release of endogenous opioids. When lidocaine reaches the spinal cord, it reduces the post-synaptic depolarisation mediated by N-methyl-d-aspartate and neurokinin receptors, thus modifying the pain response.10 N-methyl-d-aspartate blockade inhibits protein kinase C, thus reducing hyperalgesia and postoperative opioid tolerance. In animal models, lidocaine acts during the early stages of systemic inflammatory response, modulating the marginalisation, adherence and diapedesis of polymorphonuclear cells towards the site of the lesion, thus inhibiting the production of reactive oxygen species and the release of histamine. This immunomodulatory effect of the drug is achieved by blocking G protein-coupled receptors, since polymorphonuclear cells do not contain VGSCs.11 Through G protein-coupled receptors, lidocaine inhibits inflammatory processes, such as the sensitisation and lysosomal degradation of neutrophils, the production of reactive oxygen species, and the secretion of cytokines in both macrophages and glial cells. On the other hand, it can also inhibit leukocyte adhesion and migration through the endothelium by inhibiting intercellular adhesion molecules, altering the cytoskeleton, or attenuating the release of chemotactic factors. Lidocaine blocks the release of interleukin (IL) 1, IL-1, tumour necrosis factor␣ and IL-8 in polymorphonuclear cells. It also decreases circulating IL-6 and phospholipase A2 levels, both of which are involved in the disruption of the bloodbrain barrier, inflammation and brain damage.12 Lidocaine also inhibits the production of thromboxane B2 by inhibiting platelet aggregation, which reduces the risk of venous thrombosis. Finally, lidocaine has been shown to exhibit antioxidant properties by inhibiting the production of reactive oxygen species due to its interaction with phospholipid membranes and interference with mitochondrial radical formation.13
Intravenous lidocaine infusion
Pharmacokinetics and toxicity Standard dosage is an initial bolus of 1 mg/kg−1 followed by continuous perfusion of 0.5---3 mg/kg−1 /h−1 . The most widely used and best described dosage is continuous perfusion of 2 mg/kg−1 /h−1 .14 When administered intravenously, lidocaine is distributed in highly vascularised organs such as the kidney, brain and heart, and then to less vascularised organs. Around 40% of the dose is extracted temporarily by the lung, where pH is lower than in plasma. This reduces the risk of accidental toxicity in the early stages of iv administration.5 When lidocaine is administered in a 1 mg/kg bolus followed by continuous infusion of 2 mg/kg−1 /h−1 , plasma concentrations of approximately 2 g/ml−1 are obtained. Plasma concentrations of more than 5 g/ml−1 are considered toxic. These concentrations are sufficient to attenuate the sympathetic response and reduce pain and the need for inhalational agents and opioids.10 In pharmacokinetic simulations, continuous perfusion with no initial bolus takes between 4 and 8 h to reach equilibrium, with a context-sensitive half-life of 20---40 min when the infusion is completed. Lidocaine is metabolised in the liver by the P-450 system. The liver’s monoethyl-glycine-xylidide and glycine-xylidide metabolites are less effective at blocking the sodium channel. Monoethyl-glycine-xylidide has the same potential for causing antiarrhythmia and convulsions as lidocaine; however, it is rapidly metabolised to glycinexylidide. Glycine-xylidide is less active than lidocaine and its metabolite is metabolised and excreted in urine.14 Adverse effects and toxicity are extremely rare in controlled infusions.15 Circulating plasma concentrations of lidocaine are affected by dose and rate of perfusion, acid-base status, hypoalbuminemia, and liver and kidney function. Toxicity manifests with plasma concentrations of over 5 g/ml−1 , and affects the CNS and the cardiovascular system. In awake patients, toxicity manifests as numbness of the tongue, metallic taste, dizziness and tinnitus. Convulsions progressing to coma appear with concentrations greater than 10 g/ml−1 . Cardiovascular symptoms in awake patients are rare due to the lower cardiotoxicity of lidocaine compared to bupivacaine, and include QRS and PR interval prolongation, bradycardia and hypotension.14 Toxicity will require supportive measures, including oxygenation, hydration, vasopressors, inotropics, antiarrhythmics and anticonvulsants. If the patient does not respond to supportive measures, lipid infusion should be considered, starting at a dose of 1.5 ml/kg−1 at 20% and repeating this every 3---5 min up to a total dose of 8 ml/kg−1 .16
Clinical application Randomised studies, meta-analyses and systematic reviews support the use of iv lidocaine and its clinical application.15 Intravenous lidocaine infusion (bolus of 1.5 mg/kg−1 followed by 1.5---3 mg/kg−1 /h−1 ) is indicated in videolaparoscopic abdominal surgery, such as colectomy,17 cholecystectomy,18 gastrectomy,19 appendectomy,20 and bariatric surgery.21 In these procedures, lidocaine has been shown to reduce pain measured on a visual analogue scale, reduce opioid requirements and the incidence of ileus within the first 24 postoperative hours. In bariatric surgery, obese
271 patients and those with obstructive sleep apnoea syndrome are the group most likely to develop respiratory depression, so iv lidocaine is indicated in these cases.22 In open abdominal surgery23 and colorectal surgery,24,25 lidocaine exhibits the same properties as in videolaparoscopic surgery, and shortens hospital stay. Intravenous lidocaine can be used in fast-track surgery protocols, specifically, the enhanced recovery after surgery (ERAS) protocol, and also in patients in whom neuraxial blockade is contraindicated.14 Lidocaine can be continued for 24 h after surgery at a reduced dose of 1.33 mg/kg−1 h−1 .17 Computer simulations based on 3-compartment models support its use during prolonged infusion.14 Intravenous lidocaine perfusion (bolus of 1.5 mg/kg−1 followed by 2 mg/kg−1 /h−1 ) is indicated in urological procedures, such a as laparoscopic nephrectomy26 and laparoscopic nephrectomy prostatectomy,27 and also in chest surgery,28 where it has been shown to alleviate pain measured on a visual analogue scale and reduce the need for opioids. In different types of day surgery procedures, such general surgery, endocrine, breast, gynaecological, urological, plastic and otorhinolaryngology surgery,29,30 iv lidocaine was found to alleviate pain and reduce opioid requirements, but had no effect on the incidence of postoperative nausea and vomiting. Evidence suggests that good analgesia and fewer opioid requirements can shorten hospital stay. In radical mastectomy to treat breast cancer, iv lidocaine reduced the area of hyperalgesia when compared to placebo, but did not improve pain management.31 There is no evidence that lidocaine improves pain management in radical hysterectomy,32 cosmetic breast surgery,33 or hip replacement.34 The failure of pain management in these procedures could be related to differences in dosage and perfusion times, and also to differences in the variables analysed.
New fields of research Chronic postoperative pain The chronification of acute postoperative pain is a poorly understood, multifactorial process that has sparked growing interest in recent years.35 Many patients experience chronic pain after certain surgical procedures, such as thoracotomy, mastectomy or limb amputation. Recent studies have shown that opioid-induced hyperalgesia (OIH) can progress to chronic POP through complex central and/or peripheral mechanisms that alter the sensitisation of the pain stimulus. The opioids identified as potentially causing OIH in animal models and human volunteers are remifentanil, fentanyl, morphine, and diamorphine.36 The main factor associated with this phenomenon is the cumulative dose administered, particularly the effect site concentration. Similarly, Salengros et al. found that the area of allodynia around the wound measured using von Frey filaments at 24, 48 and 72 h was greater in the high dose remifentanil group (0.14---0.26 g/kg−1 /min−1 ). Finally, in the high-dose remifentanil group the number of patients with chronic pain assessed using the DN4 questionnaire for neuropathic pain was significantly higher at 1, 3, 6
272 and 9 months after surgery.37 Grigoras et al.31 , meanwhile, showed that iv lidocaine perfusion reduced the area of hyperalgesia compared with placebo in patients undergoing mastectomy for breast cancer. In another study, Terkawi et al.38 found that iv lidocaine perfusion reduced the incidence of chronic postmastectomy pain (12%) compared with placebo (30%), showing a preventive effect on the development of hyperalgesia. Some authors have speculated that the use of pharmacological strategies aimed at reducing the intensity of POP and opioid requirements could prevent progression to OIH. Opioid-sparing anaesthesia and opioid-free anaesthesia techniques are designed to avoid or minimise the development of OIH while blocking nociceptive stimuli. Backan et al.39 using opioid-free anaesthesia with propofol, dexmedetomidine and lidocaine, achieved good POP control and lower analgesic and antiemetic consumption. However, post-anaesthesia recovery was slower in this group, and new, well-designed prospective studies are needed to support the use of this anaesthetic technique.
Postoperative cognitive dysfunction Postoperative cognitive dysfunction (PCD) is defined as moderate to severe impairment of intellectual capacity caused by poorly resolved neuroinflammatory response. Growing evidence from experimental in vitro models, cell cultures, and animal models point to an interaction between surgery and anaesthesia.40 Exposure to inhalational agents can activate lytic enzymes called caspases, increase the synthesis and accumulation of -amyloid protein, and induce hyperphosphorylation of tau proteins, all of which are cellular responses consistent with the neuropathogenesis of Alzheimer’s disease.41 There is widespread consensus on the need to develop strategies that avoid or limit possible neuronal damage.42 Perfusion of iv lidocaine reduces requirements of volatile agents such as sevoflurane17,43 and desflurane,24 and thus reduces the time- and dosedependent effects of these drugs. A study in laparoscopic cholecystectomy found that administration of iv lidocaine (bolus of 1 mg/kg−1 followed by 2 mg/kg−1 /h−1 ) reduced by 19% the inspired fraction of sevoflurane needed to maintain adequate haemodynamic stability.43 In coronary bypass surgery, Wang et al. showed that the use of iv lidocaine reduced incidence of PCD compared with placebo (18.6% vs 40%; p = 0.028).44 In addition to avoiding exposure to volatile agents, animal studies in lidocaine have shown that the drug has neuroprotective properties. Perfusion of lidocaine reduced the incidence of cognitive dysfunction in rat models exposed to isoflurane. Pain is also a risk factor for the development of PCD. Some authors hypothesise that iv lidocaine infusions can reduce the risk of PCD, possibly due to its neuroprotective effects, opioid-sparing properties, and impact on pain reduction.45
Cancer recurrence Recent evidence has shown that lidocaine and other local anaesthetics may decrease the progression and recurrence of cancer through its indirect and direct effect on tumour cells. The indirect effects stem from inhibition of the neuroendocrine stress response to surgery and to a
G. Soto et al. reduction in the requirements of volatile anaesthetics and opioids.13,46 The direct effects are mediated by specific molecular actions on cancer cells. Tumour cells are known to express VGSC in a wide variety of carcinomas, including breast, cervix, colon, lung (small cell, non-small cell and mesothelioma), skin, ovarian and prostate cancer. In vitro, VGSC activity has been shown to enhance metastatic cell behaviours, such as lateral motility and invasion. This induces tumour cells to become ‘‘electrically excitable’’, becoming hyperactive and aggressive. This is known as CELEX (for cellular excitability), and is a novel hypothesis of metastatic progression.47 In this regard, Fraser et al. suggest that intra- and postoperative local anaesthetics may reduce the ability of tumour cells to metastasise by blocking VGSC and thus inhibiting their motility and invasiveness. This, in turn, could reduce the ability of the cancer cells to escape from the perioperative area and metastasise, which would increase patient survival and improve quality of life. Aside from VGSC blockage, local anaesthetics have been shown to exhibit antiproliferative properties. In vitro studies have shown that exposure to lidocaine inhibits Src protein tyrosine kinase activation in neoplastic cells, a protein involved in proliferation, migration, invasiveness and tumour metastasis.46,48 In tumour cells, lidocaine and other local anaesthetics have also been shown to inhibit the expression of intercellular adhesion molecules, which are synthesised de novo during the process of metastasis. In a recent study in cultures of breast tumour cells, Chang et al. found that lidocaine has apoptosis-inducing properties.49 With respect to clinical practice, retrospective studies with regional anaesthesia suggest that local anaesthetics might protect against tumour recurrence.50 However, more recent investigations found no differences in survival when compared to patients who did not receive local anaesthetics. These discrepancies could be due to the different routes of administration and plasma concentration of local anaesthetics, and also to differences in the behaviour to the tumours studied.
Conclusions Evidence supports the use of iv lidocaine perfusion in a wide variety of procedures, due to its analgesic, antiinflammatory and anti-hyperalgesia action. Pharmacokinetic studies have shown the most effective concentration need to achieve the desired effect, and lidocaine toxicity is rare. The advantages of lidocaine include its efficacy and effectiveness in abdominal surgery and outpatient surgery procedures, and it is also used in different fast track surgery protocols. The latest studies analyse its potential to prevent the development of chronic POP by minimising the appearance of opioid-induced hyperalgesia, and it can be used as an opioid-sparing analgesic technique. Opioid-sparing anaesthesia has been extensively researched, but prospective studies are needed to show that it improves anaesthetic outcomes compared to standard opioid-based techniques. Some authors hypothesise that iv lidocaine infusion can reduce the risk of PCD in elderly patients, potentially due to its neuroprotective effects, opioid sparing properties and impact on pain reduction. Retrospective and preliminary in vitro studies indicate that lidocaine inhibits tumour cell proliferation
Intravenous lidocaine infusion by blocking VGSC and other molecular targets. Although these findings are encouraging, further research in animals and humans is needed to develop clinical indications. Intravenous lidocaine perfusion could be indicated in a context of multimodal analgesia due to its capacity to modulate the inflammatory response produced by surgical stress, and it is considered essential in today’s perioperative practice.
Funding No funding.
Conflicts of interest The authors declare that they have no conflicts of interest.
Acknowledgement We would like to thank Hon. Prof. Dr. Gustavo Elena (RIP) (postgraduate specialisation in anaesthesiology, Faculty of Medical Sciences, National University of Rosario) for his critical review of the manuscript and his scientific contributions.
References 1. Menezes Couceiro TC, Cavalcanti Lima L, Menezes Couceiro L, Moraes Valenc ¸a M. Intravenous lidocaine to treat postoperative pain. Rev Dor São Paulo. 2014;15:55---60. 2. Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;97:534---40. 3. Tavares Mendonc ¸a F, Campos Reis M, Alvene Aguiar J, Calvano L. Systemic lidocaine for perioperative analgesia: a literature review. J Anest Inten Care Med. 2015;1:555551. 4. Yardeni IZ, Beilin B, Mayburd E, Levinson Y, Bessler H. The effect of perioperative intravenous lidocaine on postoperative pain and immune function. Anesth Analg. 2009;109:1464---9. 5. de Oliveira CM, Issy AM, Sakata RK. Intraoperative intravenous lidocaine. Rev Bras Anestesiol. 2010;60:325---33. 6. Hollmann MW, Durieux M. Local anesthetics and the inflammatory response. Anesthesiology. 2000;93:855---75. 7. Cassuto J, Sinclair R, Bonderovic M. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand. 2006;50:265---82. 8. Scholz A. Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels. Br J Anaesth. 2002;89:52---61. 9. Wood J, Boorman J, Okuse K, Baker M. Voltage-gated sodium channels and pain pathways. J Neurobiol. 2002;61:55---71. 10. Rocha Lauretti G. Mechanisms of analgesia of intravenous lidocaine. Rev Bras Anestesiol. 2008;58:280---6. 11. Minami K, Uezono Y. The recent progress in research on effects of anesthetics and analgesics on G protein-coupled receptors. J Anesth. 2013;27:284---92. 12. Lalenoh D, Bisri T, Yusuf I. Brain protection effect of lidocaine measured by interleukin-6 and phospholipase A2 concentration in epidural haematoma with moderate head injury patient. J Anesth Clin Res. 2014;5:388, http://dx.doi.org/10.4172/ 2155-6148.1000388. 13. Weinberg L, Peake B, Tan C, Nikfarjam M. Pharmacokinetics and pharmacodynamics of lignocaine: a review. World J Anesthesiol. 2015;4:17---29.
273 14. Eipe N, Gupta S, Penning J. Intravenous lidocaine for acute pain: an evidence-based clinical update. BJA Edu. 2016;16:292---8, http://dx.doi.org/10.1093/bjaed/mkw008. 15. Dunn L, Durieux M. Perioperative use of intravenous lidocaine. Anesthesiology. 2017;126:729---37. 16. Bourne E, Wright C, Royse C. A review of local anesthetic cardiotoxicity and treatment with lipid emulsion. Local Reg Anesth. 2010;3:11---9. 17. Kaba A, Laurent SR, Detroz BJ, Sessler DI, Durieux ME, Lamy ML, et al. Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy. Anesthesiology. 2007;106:11---8. 18. Lauwick S, Kim DJ, Michelagnoli G, Mistraletti G, Feldman L, Fried G, et al. Intraoperative infusion of lidocaine reduces postoperative fentanyl requirements in patients undergoing laparoscopic cholecystectomy. Can J Anaesth. 2008;55:754---60. 19. Kim TH, Kang H, Choi YS, Park JM, Chi KC, Shin HY, et al. Pre- and intraoperative lidocaine injection for preemptive analgesics in laparoscopic gastrectomy: a prospective, randomized, doubleblind, placebo-controlled study. J Laparoendosc Adv Surg Tech A. 2013;23:663---8. 20. Kim TH, Kang H, Hong JH, Park JS, Baek CW, Kim JY, et al. Intraperitoneal and intravenous lidocaine for effective pain relief after laparoscopic appendectomy: a prospective, randomized, double-blind, placebo-controlled study. Surg Endosc. 2011;25:3183---90. 21. De Oliveira GS Jr, Duncan K, Fitzgerald P, Nader A, Gould RW, McCarthy RJ. Systemic lidocaine to improve quality of recovery after laparoscopic bariatric surgery: a randomized doubleblinded placebo-controlled trial. Obes Surg. 2014;24:212---8. 22. Chung F. Obstructive sleep apnea patients: a challenge for anesthesiologists. IARS 2010 review lectures. IARS; 2010. Available from: course http://www.iars.org/assets/1/7/IARS-RCL10 16.pdf [accessed 3.3.17]. 23. Koppert W, Weigand M, Neumann F, Sittl R, Schuettler J, Schmelz M, et al. Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg. 2004;98:1050---5. 24. Kuo CP, Jao SW, Chen KM, Wong CS, Yeh CC, Sheen MJ, et al. Comparison of the effects of thoracic epidural analgesia and i.v. infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery. Br J Anaesth. 2006;97:640---6. 25. Herroeder S, Pecher S, Schönherr ME, Kaulitz G, Hahnenkamp K, Friess H, et al. Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial. Ann Surg. 2007;246:192---200. 26. Tauzin-Fin P, Bernard O, Sesay M, Biais M, Richebe P, Quinart A, et al. Benefits of intravenous lidocaine on post-operative pain and acute rehabilitation after laparoscopic nephrectomy. J Anaesth Clin Pharm. 2014;30:366---72,http://dx.doi.org/ 10.4103/0970-9185.137269. 27. Lauwick S, Kim DJ, Mistraletti G, Carli F. Functional walking capacity as an outcome measure of laparoscopic prostatectomy: the effect of lidocaine infusion. Br J Anaesth. 2009;103:213---9. 28. Cui W, Li Y, Li S, Wang R, Li J. Systemic administration of lidocaine reduces morphine requirements and postoperative pain of patients undergoing thoracic surgery after propofol-remifentanil-based anaesthesia. Eur J Anaesthesiol. 2010;27:41---6. 29. 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;109:1805---8. 30. De Oliveira GS Jr, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of
274
31.
32.
33.
34.
35. 36.
37.
38.
39.
40.
G. Soto et al. recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012;115:262---7. Grigoras A, Lee P, Sattar F, Shorten G. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. Clin J Pain. 2012;28:567---72. Bryson GL, Charapov I, Krolczyk G, Taljaard M, Reid D. Intravenous lidocaine does not reduce length of hospital stay following abdominal hysterectomy. Can J Anaesth. 2010;57:759---66. Choi S, Kim M, Jeong H, Lee JJ. Effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery. Korean J Anesth. 2012;62:429---34. Martin F, Cherif K, Gentili ME, Enel D, Abe E, Alvarez JC, et al. Lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty. Anesthesiology. 2008;109:118---23. Macrae W. Chronic pain after surgery. Br J Anesth. 2001;87:88---98, http://dx.doi.org/10.1093/bja/87.1.88. Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112:991---1004, http://dx.doi.org/10.1093/bja/aeu137. Salengros JC, Huybrechts I, Ducart A, Faraoni D, Marsal C, Barvais L, et al. Different anesthetic techniques associated with different incidences of chronic post-thoracotomy pain: low-dose remifentanil plus presurgical epidural analgesia is preferable to high-dose remifentanil with postsurgical epidural analgesia. J Cardiothorac Vasc Anesth. 2010;24:608---16. Terkawi AS, Sharma S, Durieux ME, Thammishetti S, Brenin D, Tiouririne M. Perioperative lidocaine infusion reduces the incidence of post-mastectomy chronic pain: a doubleblind, placebo-controlled randomized trial. Pain Phys. 2015;18:E139---46. Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, et al. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Rev Bras Anestesiol. 2015;65:191---9. Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106:161---78, http://dx.doi.org/10.1093/bmb/ldt006.
41. Jiang J, Jiang H. Effect of the inhaled anesthetics isoflurane, sevoflurane and desflurane on the neuropathogenesis of Alzheimer’s disease (review). Mol Med Rep. 2015;12:3---12, http://dx.doi.org/10.3892/mmr.2015.3424. 42. Jevtovic-Todorovic V, Absalom A, Blomgren K, Brambrink B, Crosby G, Culley D, et al. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth. 2013;111:143---51, http://dx.doi.org/10.1093/bja/aet177. 43. Calero F, Pignolo F, Soto G. Effect of intravenous lidocaine infusion on sevoflurane and fentanyl consumption, hemodynamic response and ventricular repolarization. Rev Argent Anestesiol. 2016;74:49---56. 44. Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg. 2002;95:1134---41. 45. Durieux M, Ford J. Expanding your anaesthetic technique: an overview on the efficacy of using a lidocaine infusion as part of a balanced anaesthetic. Up Anesth. 2014;29:24---7. Available from: http://www.wfsahq.org/ resources/update-in-anaesthesia 46. Votta-Velis E, Piegeler T, Minshall R, Aguirre J, BeckSchimmer B, Schwartz D, et al. Regional anaesthesia and cancer metastases: the implication of local anaesthetics. Acta Anaesthesiol Scand. 2013;57:1211---29, http://dx.doi.org/ 10.1111/aas.12210. 47. Fraser S, Foo I, Djamgoz M. Local anaesthetic use in cancer surgery and disease recurrence: role of voltagegated sodium channels? Br J Anaesth. 2014;113:899---902, http://dx.doi.org/10.1093/bja/aeu221. 48. Piegeler T, Votta-Velis EG, Liu G, Place AT, Schwartz DE, Beck-Schimmer B, et al. Antimetastatic potential of amidelinked local anesthetics: inhibition of lung adenocarcinoma cell migration and inflammatory Src signaling independent of sodium channel blockade. Anesthesiology. 2012;117: 548---59. 49. Chang Y, Liu CH, Chen M, Hsu Y, Chen S, Lin CH, et al. Local anesthetics induce apoptosis in human breast tumor cells. Anesth Analg. 2014;118:116---24. 50. Sekandarzad MW, van Zundert AAJ, Lirk PB, Doonerbal CW, Hollmann MW. Perioperative anesthesia care and tumor progression. Anesth Analg. 2017;124:1697---708.
