Novas utilizações da cetamina para tratamento da dor somática e seus mecanismos de ação
DOI:
https://doi.org/10.26605/medvet-v12n2-2360Keywords:
analgesia, anti-inflamatório, anestésico.Abstract
A cetamina é classificada como anestésico dissociativo, seu emprego caiu em desuso graças a formulação de novos fármacos com menor apresentação de efeitos adversos. No entanto, estudos recentes têm apontado para qualidades até então desconhecidas da cetamina. O objetivo dessa revisão foi relatar os efeitos farmacológicos antálgicos periféricos e centrais da cetamina, bem como sua possível aplicabilidade clínica para o tratamento da dor somática. Vários estudos vêm apontando para uma função antiinflamatória, também como adjuvante de anestésicos locais, ou ainda que baixas doses para propriedades analgésicas apenas, sem observação de efeitos adversos e via de administração intranasal como uma opção não invasiva de administração. Assim, a cetamia tem se tornado uma excelente alternativa para os protocolos multimodais de tratamento antinociceptivo, e não somente um anestésico dissociativo de baixo custo e muitos efeitos adversos. Conclui-se que a cetamina possui diferentes mecanismos de ação dos já elucidados, e que sua aplicabilidade clínica pode ser diferencial quando utilizada em um protocolo analgésico multimodal, melhorando a qualidade de tratamento aos pacientes.Downloads
References
Abbasi, S.; Bidi, N.; Mahshidfar, B.; Hafezimoghadam, P.; Rezai, M.; Mofidi, M.; Farsi, D. Canlow-dose of ketamine reduce the need for morphine in renal colic? A doubleblind randomized clinical trial. American Journal of Emergency Medicine, 36(6): 376379, 2017.
Abdel-Ghaffar, H.S.; Salem, M.A.M. Safety and analgesic efficacy of pre-empitive intranasal ketamine versus intranasal fentanyl in patients undergoing endescopic nasal surgery. Journal of American Science, 8(3): 430-436, 2012.
Allen, C.A.; Ivester, J.R. Ketamine for pain management—side effects & potential adverse events. Pain Management Nursing, 18(6): 372-377, 2017.
Andolfatto, G.; Willman, E.; Joo, D.; Miller, P.; Wong, W.; Koehn, M.; Dobson, R.; Angus, E.; Moadebi, S. Intranasal ketamine for analgesia in the emergencydepartment: a prospective observational series. Society for Academic Emergency Medicine, 20(10): 1050-1054, 2013.
Ayoglu, H.; Altunkaya A.H.; Bayar A.; Turan I.O.; Ozer, Y.; Ege, A. The effect of intra articular combinations of tramadol and ropivacaine with ketamine on postoperative pain after arthroscopic meniscectomy. Archives of Orthopaedic and Trauma Surgery, 130: 307312, 2010.
Bailard, N.S.; Ortiz, J.; Flores, R.A. Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations. American Journal of Health-System Pharmacy, 71(5): 373-385, 2014. Bajwa, S.J.S. Ketamine-the confluence of old and recent concepts. Journal of Pain & Relief, 6: 283, 2017.
Berry, S.H., Anestésicos Injetáveis. In: Grimm, K. A.; Lamont, L. A.; Tranquilli, W. J.; Greene, S. A .; Robertson, S. A., Lumb & Jones Anestesiologia e Analgesia em Veterinária, Rio de Janeiro: Guanabara Koogan, 2017, p. 271-290.
Boettger, M.K.; Weber, K.; Gajda, M.; Bräuer, R.; Schaible, H. Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis. Brain, Behavior, and Immunity, 24(3): 474-485, 2010.
Brau, M.E.; Sander, F.; Vargel, W.; Hemelmann, G. Blocking mechanisms of ketamine and its enantiomers in enzymatically demyelinated peripheral nerve as revealed by single-channel experiments. Anesthesiology, 86(2): 903, 1997.
Brockmeyer, D.M.; Kengid, J.J. Seletective effects of ketamine on amino acid-mediated pathways in neonatal rat spinal cord. British Journal of Anaesthesia, 74(1): 79, 1995.
Corssen, G.; Miyasaka, M.; Domino, E.F., Changing concepts in pain control during surgery: Dissociative anesthesia with CI-581-A progress report. Anestheanlg, 47(6): 746, 1968.
Christensen, K.; Rogers, E.; Green, G.A.; Hamilton, D.A.; Mermelsteins, F.; Liao, E.; Writght, C.; Carr, D.B. Safety and efficacy of intranasal ketamine for acute postoperative pain. Acute Pain Elsevier, 9(4): 183-192, 2007. Dale, O.; Somogyi, A.A.; Li, Y.; Sullivan, T.; Shavit,Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and metaanalysis. Pain Medicine, 115(4), 2012.
D’Alonso, R.C.; Bennett-Guerrero, E.; Podgoreanu, M.; D’Amico, T.A.; Harpole, D.H.; Shaw, A.D. A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery. Journal of Anesthesia, 25(5): 672-678, 2011.
DeRossi, R.; Benites, A.P.; Ferreira, J.Z.; Neto, J.M.; Hermeto, L.C. Efeitos da cetamina e lidocaína peridural lombossacra em gatos sedados com xilazina. Journal of the South African Veterinary Association, 80(2): 79-83, 2009.
DeRossi, R.; Frazílio, F.O.; Jardim, P.H.; Martins, A.R.; Schimidt, R.; Negrini-Net, J.M. Evaluation of thoracic epidural analgesia induced by lidocaine, ketamine, or both administered via a lumbosacral approach in dogs. American Journal of Veterinary Research, 72(12): 1580-1585, 2011. El-Khateeb, O.E. Caudal ketamine for relief of pain following anorectal surgery. In: Domino EF. Status of Ketamine In Anesthesiology. Ann Arbor, 1990.
Fantoni, D.T.; Cortopassi, S.R.G.; Bernardi, M.M. Anestésicos Intravenosos e Outros Parenterais. In: Spinosa, H. S.; Górniak, S. L.; Bernardir, M. M., Farmacologia aplicada à medicina veterinária. Rio de Janeiro: Guanabara Koogan, 2011. p.129-139.
Farmawy, M.S.; Rashad, M.M. Preemptive analgesia by peritonsillar ketamine versus ropivacaine for post-tonsillectomy pain in children. Egyptian Journal of Anaesthesia, 30(1): 1-5, 2014.
Farnia, M.R.; Jalali, A.; Vahidi, E.; Momeni, M.; Seyedhosseini, J.; Saeedi, M. Comparison of intranasal ketamine versus intravenous morphine in reducing pain in patients with renal colic. American Journal of Emergency Medicine, 35(3): 434-437, 2016.
Fielding, C.L.; Brumbaugh, G.W.; Matthews, N.S.; Peck, K.E.; Roussel, A.J. Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses. American Journal of Veterinary Research, 67(9): 1484-1490, 2006.
Fu, E.S.; Miguel, R. Scharf, J.E. Preempitive ketamine decreases post-operatorative narcotic requirements in patients undergoing abdominal surgery. Anesthesia & Analgesia, 84(5): 1294, 1997.
Gomes De Segura, I.A.; DeRossi, R.; Santos, M.; San-Roman, J.L.; Tendillo, F.J. Epidural injections of ketamine for perineal analgesia in the horse. Veterinary Surgery, 27(4): 217-384, 1998.
Guinto-Enriquez, G.; Esqiquez, R.Y.; Reyedes De Castro, I. Epidural injection of ketamine hydrochloride: Na experimental study in rats. In: Domino EF, Ed. Status of Ketamine in Anesthesiology, Ann Arbor, 1990. Hong, B.; Lim, C.S.; Kim, Y.H.; Lee, J.U.; Kim, Y.M.; Jung, C.; Jo, Y. Comparison of topical and non-ketamine ropivacaine in post-surgical pain in children submitted to tonsillectomy: a randomized, double-blind controlled trial. Journal of Anesthesia, 31(4): 559-564, 2017.
Hosseini Jahromi, S.A.; Hosseini Valami, S.M.; Hatamian, S. Comparison between effect of lidocaine, morphine and ketamine spray on post-tonsillectomy pain in children. Anesthesiology and Pain Medicine, 2(1): 1721, 2012.
Kawamata, T.; Omote, K.; Sonoda, H.; Kawamata, M.; Namiki, A. Analgesic mechanisms of ketamine in the presence and absence of peripheral inflammation. Anesthesiology, 93(2): 520-528, 2000.
Khajavi, M.R.; Navardi, M.; Moharari, R.S.; Pourfakhr, P.; Khalili, N.; Etezadi, F.; Imani, F. Combined ketamine-tramadol subcutaneous wound infiltration for multimodal postoperative analgesia: a double-blinded, randomized controlled trial after renal surgery. Anesthesiology and Pain Medicine, 6(5), 2016.
Kitahana, L.M.; Taub, A.; Kosaka, Y. Laminaspecific suppressions of dorsal-horn unit activity by ketamina hydrockloride. Anesthesiology, 38(1):4-11, 1973.
Kock, M.D.; Loix, S.; Lavand'homme, P. Ketamine and peripheral inflammation. CNS Neuroscience & Therapeutics, 19: 403-410, 2013. Kwok, R.F.K.; Lim, L.; Chan, M.T.V.; Gin T.; Chiu W.K.Y. Preoperative ketamine improves postoperative analgesia after gynaecologic laparascopic surgery. Anesthesia & Analgesia, 98(4): 1044-1049, 2004. Lankveld, D.P.K.; Bull, S.; Dijki, P.V.; FinkGremmels, J.; Hellebrekers L.J. Ketamine inhibits LPS-induced tumour necrosis factoralpha and interleukin-6 in na equine macrophage cell line. Veterinary Research, 36(2): 257-262, 2005.
Lee, I.O.; Kim, W.K.; Kong, M.H.; Lee, M.K.; Kim, N.S.; Choi Y.S.; Lim S.H. No enhancement of sensory and motor blockade by ketamine added to ropivacaineinterscalene brachial plexus blockade. Acta Anaesthesiologica Scandinavica, 46(8): 821826, 2002.
Liao, E.; Mermelsteins, F.; Wright, C.; Carr, D.B. Relative Analgesic Potencies of Intranasal Ketamine and Intranasal Morphine Compared to Intravenous Morphine. American Academy of Pain Medicine, 2008.
Lin, H., Anestésicos Dissociativos. In: Tranquilli, W.J.; Thurmon, J.C.; Grimm, K.A. Anestesiologia e Analgesia Veterinária. São Paulo: Roca, 2013. p. 335-384.
Liu, F.L.; Chen, T.L.; Chen, R.M. Mecanismo de imunossupressão induzida por cetamina. Acta Anaesthesiologica Taiwanica, 50: 172-177, 2012. Lopez-Sanroman, F.J.; Cruz, J.M.; Santos, M.; Mazzini, R.A.; Tabanera, A.; Tendillo, F.J. Evaluations of the local analgesic effect of ketamine in the palmar digital nerve block at the base of the proximal sesamoid (abaxial sesamoid block) in horses. American Journal of Veterinary Research, 64(4): 475-478, 2003.
Luft, A.; Mendes, F.F. S (+) Cetamina em Baixas Doses: Atualização. Revista Brasileira de Anestesiologia, 55(4), 2005.
Luna, S.P.L.; Neto, F.J.T.; Aguiar, A.J.A. Anestesiologia em Pequenos Animais. Botucatu: Fmvz Unesp, 2016.
Massopust, L.C.; Wolin, L.R.; Albin, M.S. The effects of a new phencyclidine derivative and diazepione derivative on the electroencephalographic and behavioral responses in the cat. Tower International Technomedical Journal of Life Sciences, 3(1), 1973.
Marjani, M.; Akbarinejad, V.; Bagheri, M. Comparison of intranasal and intramuscular ketamine midazolam combination in cats, Veterinary Anaesthesia and Analgesia, 42(2): 178-181, 2015.
Moharari R.S.; Valizade, A.; Najafi, A.; Etezadi, F.; Hosseini, S.R.; Khasharayar, P.; Khajavi, M.R.; Mojtahedzadeh, M. Analgesic efficacy of nephrostomy tract infiltration of bupivacaine and ketamine after tubeless percutaneous nephrolithotomy: a prospective randomized trial. Iranian Journal of Pharmaceutical Research, 15(2): 619-626, 2016.
Moharari, R.S.; Najafi, A.; Khajavi, M.R.; Moharari, G.S.; Nikoobakht M.R. Intraurethral instillation of ketamine for male rigid cystoscopy. Journal of Endourology, 24(12): 2033-2036, 2010.
Miyasaka M.; Domino E.F. Neuronal mechanisms of ketamine induced anesthesia. International Journal of Neuropharmacology, 7(6): 557573, 1968.
Motov, S.; Mai, M.; Pushkar, I.; Likourezoz, A.; Drapkin, J.; Yasavolian, M.; Brady, J.; Homel, P.; Fromm, C. Prospective randomized, doubledummy Trial comparing intravenous push dose of low dose ketamine to short infusion of low dose ketamine for treatment of moderate to severe pain in the emergency department. American Journal of Emergency Medicine, 35(8): 1095-1100, 2017.
Muir, W.W. NMDA receptor antagonists and pain: ketamine. Veterinary Clinics of North America: Equine Practice, 26(3): 565-578, 2010.
Ohtani, M.; Kikuchi, H.; Kitahana, L.M.; Taub, A.; Toyooka, H.; Hannaoka, K.; Dohi, S. Effects of ketamine on nociceptive cells in the mediai
medullary reticular formations of the cat. Anesthesiology, 51(5): 414-427, 1979.
Othman, A.H.; El-Rahman, A.M.A.; El Sherif, F. Efficacy and safety of ketamine added to local anesthetic in modified pectoral block for management of postoperative pain in patients undergoing modified radical mastectomy. Pain Physician, 19(7): 485-494, 2016.
Parvizrad, R.; Pakniyat, A.; Malekianadeh, B. Comparing the analgesic effect of intranasal with intravenous ketamine in isolated orthopedic trauma: A randomized clinical trial. Turkish Journal of Emergency Medicine, 17(3): 99-103, 2017.
Pederson, J.L.; Galle T.S.; Kehlet, H.M. Peripheral analgesic effects of ketamine in acute inflammatory pain. Anesthesiology, 89(1): 5866, 1998. Preskorn, S.H. Ketamine: the hopes and obstacles. Biological Psychiatry, 72: 522-523, 2012.
Pourmand, A.; Mazer-Amirshasi, M.; Royall, C.; Alhawas, R.; Shesser, R. Low dose ketamine use in the emergency department, a new direction in pain management. The American Journal of Emergency Medicine, 35(6): 918921, 2017.
Rascón-Martínez, D.M.; Carrillo-Torres, O.; Ramos-Nataren, R.G.; Rendón-Jaramillo, L. Advantages of ketamine as a perioperative analgesic. Revista Médica del Hospital General de México, 79(4), 2016.
Rédua, M.A.; Valvadão, C.A.A.; Duque, J. C.; Balestrero, L.T. The pré-emptive effect of ketamine on wound sensitivity in horses tested by using Von Frey filaments. Veterinary Anaesthesia and Analgesia, 29(4): 200-206, 2002.
Robson, M.J.; Elliot, M.; Seminerio, M. J.; Matsumoto, R.R. Evaluation of sigma receptors (σ) on antidepressant effects of ketamine in vitro and in vivo. European Neuropsychopharmacology, 22(4): 308317.2012. Romagnoli, N.; Bektas, R.N.; Kutter, A.P.; Barbarossa, A.; Roncada, P.; Hartnack, S.; Bettschart-Wolfensberger, R. Pharmacokinetics of ketamine and norketamine enantiomers after racemic or S-ketamine IV bolus administration in dogs during sevoflurane anaesthesia. Research in Veterinary Science, 112: 208– 213, 2017.
Rosseland, L.A.; Stubhand, A.; Sandberg, L.; Breivik, H. Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline. Pain, 104(1-2): 25-42, 2003.
Sawyer, D.C.; Rech, R.H.; Durham, R.A. Does ketamine provide adequate visceral anlgesia when used alone or in combination with acepromazine, diazepam, or butorphanol in cats. Journal of the American Animal Hospital Association, 29: 257, 1993.
Sawyer, D.C.; Rech, R.H.; Durham, R.A. Efects of ketamine and combinations with acetylpromazine, diazepam, or butorphanol on visceral nocicptionsin the cat.Em: Domino E.F, Ed. Status of ketamine in anesthesiology, Ann Arbor, 1990.
Stoetzer, C.; Martell, C.; De La Roche, J.; Leffler, A. Inhibition of voltage-gated na+ channels by bupivacaine is enhanced by the adjuvants buprenorphine, ketamine, and clonidine. Regional Anesthesia and Pain Medicine, 42(4):462-468, 2017.
Stubburg, A.; Breivik, H.; Eide, P.K.; Kreunen, M.; Foss, A. Mapping of punctuavehyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery. Acta Anaesthesiologica Scandinavica, 41: 1124, 1997.
Tsao, C.; Wu, C. Modulating effects of ketamine on inflammatory response in sepsis. Acta Anaesthesiologica Taiwanica, 145-146, 2012.
TvwrkoY, M.; Oren, M.; Vaskovich, M. Dashkovvsky, I.; Kissin, I. Ketamine enhances local anesthesic and analgesic effects of bupivacaine by-peripheral mechanism: A study in postoperative patients. Neuroscience Letters. 215(1): 5-8, 1996.
Warncke, T.; Jorum, F.; Stubhaug, A. Local treatment with the N-methyl-D-aspartate receptor antagonist, ketamine, inhibits development of secondary hyperalgesia in man by a peripheral actions. Neuroscience Letters, 227(1): 1-4, 1996.
Woolfe, C.J.; Thompson, S.W.N. The inductions and maintenance of central sensitizations is dependent on N-MethylD-Aspartate receptor activations: Implications for the treatament of post-injury pain hypersensibivity state, Pain, 44(3): 293-299, 1991.
Xingwei, X.; Xin, G.; Peng, Z.; Tao, F.; Bowen, D.; Xiaoming, K.; Wu, J.; Ning, L.; Jiesbou, L. Low-dose ketamine pretreatment reduces oxidative damage and inammatory response following CO2 pneumoperitoneum in rats. Clinical and Investigative Medicine, 37(3), 2014.
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