Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942002000100005
Brazilian Journal of Anesthesiology
Scientific Article

Avaliação clínica comparativa entre a cetamina e a clonidina por via peridural no tratamento da dor crônica neuropática

Epidural ketamine versus epidural clonidine as therapeutic for refractory neuropathic chronic pain

Gabriela Rocha Lauretti; Alexandre de Menezes Rodrigues; Josenília Maria Alves Gomes; Marlene Paulino dos Reis

Downloads: 1
Views: 779

Resumo

JUSTIFICATIVA E OBJETIVOS: A dor crônica resulta em resposta aumentada dos neurônios do corno dorsal da medula espinhal, devido à ação de diferentes mediadores liberados pelas terminações neuronais, incluindo agonistas para os receptores N-metil-D-aspartato. Além das vias ascendentes sensitivas, vias descendentes inibitórias modulam a sensação de dor, incluindo a participação de a2-agonistas localizados nos aferentes primários e na medula espinal. Este estudo visou avaliar o efeito antinociceptivo da cetamina (antagonista do receptor N-metil-D-aspartato) e da clonidina (a2-agonista) administrada por via peridural, no tratamento da dor crônica neuropática. MÉTODO: Vinte e seis pacientes adultos com queixa de dor tipo neuropática, não-responsiva aos tratamentos convencionais, foram de forma prospectiva, aleatória e duplamente encoberta, divididos em dois grupos. Todos os pacientes fizeram uso de 50-75 mg de amitriptilina por via oral diariamente. A dor foi avaliada utilizando-se a escala analógica visual (EAV) de 10 cm, em que “zero” correspondeu à “ausência de dor” e “dez” à “pior dor imaginável”. Um cateter peridural foi inserido na região lombar, e as medicações por via peridural foram administradas em intervalos de 8 horas, durante três semanas. O Grupo Cetamina recebeu 0,1 mg.kg-1 de cetamina sem conservante, seguida da administração de 30 mg de lidocaína a 1%, em cada aplicação. O Grupo Clonidina recebeu 30 µg de clonidina sem conservante, seguida da administração de 30 mg de lidocaína a 1%, em cada aplicação. RESULTADOS: Vinte e três pacientes fizeram parte da avaliação final. A administração de cetamina ou clonidina por via peridural, nas doses propostas, resultou em analgesia durante todo o período da manutenção do cateter peridural (EAV inicial 8-10 cm versus EAV final 0-3 cm) (p < 0,002). Após a retirada do cateter peridural, os valores numéricos da EAV mantiveram-se entre 0-3 cm durante 2 a 5 semanas. CONCLUSÕES: A administração de cetamina ou clonidina por via peridural resultou em ação antinociceptiva em pacientes com dor crônica neuropática, não-responsiva aos tratamentos convencionais, representando alternativas eficazes, quando o tratamento convencional não obteve sucesso.

Palavras-chave

ANALGÉSICOS, DOR, Crônica, HIPNÓTICOS, TÉCNICAS ANESTÉSICAS, Regional

Abstract

BACKGROUND AND OBJECTIVES: Chronic pain results in an increased response of spinal cord dorsal horn neurons due to the action of several mediators released by neuronal terminals, including the agonists of N-methyl-D-aspartate receptors. In addition to sensory ascending pathways, inhibitory descending pathways modulate pain, including a2-adrenoceptors located on primary afferent terminals and on the spinal cord. This study was designed to investigate the anti-noxious effects of epidural ketamine (N-methyl-D-aspartate antagonist) or epidural clonidine (a2-adrenergic agonist) in the treatment of neuropathic chronic pain. METHODS: Twenty-six adult patients, with neuropathic chronic pain not responsive to conservative therapy, were randomly divided into two groups in this prospective double-blind study. All patients were regularly taking 50-75 mg oral amitriptyline at bedtime. Pain was evaluated through a 10 cm visual analog scale (VAS), with “zero” corresponding to “no pain” and 10 to “the worst possible pain”. A lumbar epidural catheter was inserted and test drugs were administered at 8 hour-intervals during 3 weeks. The ketamine group (KG) was given each time 1 mg.kg-1 preservative-free ketamine followed by 30 mg of 1% lidocaine. The clonidine group (Clo G) was given 30 µg preservative-free clonidine followed by 30 mg of 1% lidocaine (3 ml). RESULTS: Twenty-three patients were evaluated (KG-n=10; Clo G-n=13). Epidural administration of ketamine or clonidine in the proposed doses resulted in analgesia during epidural catheter maintenance (initial VAS 8-10 cm versus final VAS 0-3 cm) (p < 0.002). VAS scores remained maintained between 0 and 3 cm from 2 to 5 weeks following epidural catheter removal. CONCLUSIONS: Epidural ketamine or clonidine resulted in analgesia for neuropathic chronic pain refractory to conservative treatment and are effective alternatives when conventional treatment fails.

Keywords

ANALGESICS, ANESTHETIC TECHNIQUES, Regional, HYPNOTICS, PAIN, Chronic

References

Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain. 1983;17:321-339.

Cousins MJ. Pain: the past, present and future of Anesthesiology?. Anesthesiology. 1999;91:538-551.

Eisenach JC, DuPen S, Dubois M. Peridural clonidine analgesia for intractable cancer pain. Pain. 1995;61:391-399.

Lauretti GR, Gomes JMA, Reis MP. Low doses of peridural ketamine or neostigmine, but not midazolam, improve morphine analgesia in peridural terminal cancer pain therapy. J Clin Anesth. 1999;11:663-668.

Persson J, Axelsson G, Hallin RG. Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to a central sensitization. Pain. 1995;60:217-222.

Findlow D, Aldridge LM, Doyle E. Comparison of caudal block using bupivacaine and ketamine with ilioinguinal nerve block for orchidopexy in children. Anaesthesia. 1997;52:1090-1110.

Cook B, Grubb DJ, Aldridge LA. Comparison of the effects of adrenaline, clonidine and ketamine on the duration of caudal analgesia produced by bupivacaine in children. Br J Anaesth. 1995;75:698-701.

Iida H, Dohi S, Tanahashi T. Spinal conduction block by intrathecal ketamine in dogs. Anesth Analg. 1997;85:106-110.

Pocket S. Spinal cord synaptic plasticity and chronic pain. Anesth Analg. 1995;80:173-179.

Ghorpade A, Advokat C. Evidence of a role for N-methyl-D-as-partate (NMDA) receptors in the facilitation of tail withdrawal after spinal transection. Pharmacol Bioch Behav. 1994;48:175-181.

Orser BA, Pennefather PS, MacDonald JF. Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors. Anesthesiology. 1997;86:903-917.

Hurstveit O, Maurset A, Oye I. Interaction of the chiral forms of ketamine with opioid, phenciclidine, and muscarinic receptors. Pharmacol Toxicol. 1995;77:355-359.

Ashford ML, Boden P, Ramsey RL. Enhancement of desensitization of quisqualate-type glutamate receptor by the dissociative anaesthetic ketamine. J Exp Biol. 1989;141:73-86.

Crisp T, Perroti JM, Smith DL. The local monoaminergic dependence of spinal ketamine. Eur J Pharmacol. 1991;194:167-172.

Yamakage M, Hirshman CA, Croxton TL. Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca++ channels in porcine tracheal smooth muscle cells. Anesthesiology. 1996;83:1274-1282.

Smith DJ, Bouchal RL, DeSanctis CA. Properties of the interaction between ketamine and opiate binding sites in vivo and in vitro. Neuropharmacol. 1987;26:1253-1260.

De Kock MD, Eisenach J, Tong C. Analgesic doses of intrathecal but not intravenous clonidine increase acetylcholine in cerebrospinal fluid in humans. Anesth Analg. 1997;84:800-803.

Chassard D, Mathon L, Dailler F. Extradural clonidine combined with sufentanil and 0.0625% bupivacaine for analgesia in labor. Br J Anaesth. 1996;77:458-462.

Yaksh TL, Pogrel JW, Lee YW. Reversal of nerve ligation-induced allodynia by spinal alpha-2 adrenoceptor agonists. J Pharmacol Exp Ther. 1995;272:207-214.

Davis KD, Treede RD, Raja SN. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain. 1991;47:309-317.

Rauck RL, Eisenach JC, Jackson K. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1993;79:1163-1169.

Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Anesthesia. 1999;54:146-165.

Klimscha W, Tong C, Eisenach JC. Intrathecal a2-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. Anesthesiology. 1997;87:110-116.

Smith MS, Shambra UB, Wilson K. Alpha1-adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha 1-adrenergic receptor subtypes at four distinct levels. Mol Brain Res. 1999;63:254-261.

Smith MS, Shambra UB, Wilson KH. Alpha 2 adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha 2-adrenergic receptor subtypes at four distinct levels. Mol Brain Res. 1995;34:109-117.

Ongiocco RR, Richardson CD, Rudner XL. Alpha-2 adrenergic receptors in human dorsal root ganglia: predominance of a2b and a2c subtype mRNAs. Anesthesiology. 2000;92:968-976.

Nagy I, Woolf CJ. Lignocaine selectivity reduces C fibre-evoked neuronal activity in rat spinal cord in vitro by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated post-synaptic depolarizations; implications for the development of novel centrally acting analgesics. Pain. 1996;64:59-70.

Bartolini A, Galli A, Ghelardini C. Antinociception induced by systemic administration of local anesthetics depends on a central cholinergic mechanism. Br J Pharmacol. 1987;92:711-721.

Biella G, Sotgiu ML. Central effects of systemic lidocaine mediated by glycine spinal receptors: an iontophoretic study in the rat spinal cord. Brain Res. 1993;603:201-206.

5dd59a070e8825b10bc8fca6 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections