Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942011000600006
Brazilian Journal of Anesthesiology
Scientific Article

Avaliação do uso de microesferas de bupivacaína em excesso enantiomérico de 50% após bloqueio do nervo ciático de ratos

Assessing the use of 50% enantiomeric excess bupivacaine-loaded microspheres after sciatic nerve block in rats

Rohnelt Machado de Oliveira; Pedro Paulo Tanaka; Sergio Bernardo Tenorio

http://dx.doi.org/10.1590/S0034-70942011000600006 Braz J Anesthesiol, vol.61, n6, p.741-747, 2011
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Resumo

JUSTIFICATIVA E OBJETIVOS: Alcançar melhores benefícios terapêuticos dos anestésicos locais no controle da dor pós-operatória, através de carreadores de liberação controlada. Este estudo teve por objetivo a comparação das características dos bloqueios sensitivo e motor entre microesferas sem anestésico local; microesferas com bupivacaína racêmica encapsulada; microesferas com bupivacaína em excesso enantiomérico 50% e bupivacaína em excesso enantiomérico 50% sem as microesferas. MÉTODO: Ratos (Wistar), alocados em quatro grupos: A (Microesfera); B (Microesfera de bupivacaína S50-R50); C (Microesfera de Bupivacaína em excesso enantiomérico de 50%); D (Bupivacaína em excesso enantiomérico de 50%). A anestesia inalatória, realizada previamente ao bloqueio do nervo ciático (halotano a 2% e O2 a 100%). O bloqueio sensorial foi medido pelo tempo exigido para cada rato retirar a pata de uma placa quente a 56ºC (positivo > 4 s). O bloqueio motor foi medido pelo tempo entre a injeção do medicamento até a recuperação do escore 2 de critério estabelecido. RESULTADOS: Nos grupos B, C e D a resposta sensitiva foi significativamente mais frequente do que no Grupo A (p < 0,001). Entre os Grupos B, C e D não se observam diferenças estatisticamente significativas de resposta positiva ao teste sensitivo (p > 0,05). Nos Grupos B, C e D, a resposta ao teste motor também foi significativamente mais frequente do que no grupo A (p = 0,02). Nos Grupos B e D, observou-se tendência de maior positividade ao teste motor que no Grupo C (p = 0,10). CONCLUSÕES: A liberação controlada de microesfera de bupivacaína em excesso enantiomérico de 50% apresentou resultado semelhante em relação à analgesia quando comparado às outras formulações anestésicas e menor bloqueio motor.

Palavras-chave

ANESTÉSICOS, ANESTÉSICOS, Rato, DOR

Abstract

BACKGROUND AND OBJECTIVES: To achieve better therapeutic benefits of local anesthetics in the control of postoperative pain through controlled-release carrier. The objective of this study was to compare the characteristics of sensory and motor blockade between microspheres without local anesthetic: racemic bupivacaine-loaded microspheres; 50% enantiomeric excess bupivacaine-loaded microspheres; and free 50% enantiomeric excess bupivacaine. METHODS: Wistar rats were distributed into four groups: A (Microsphere); B (S50-R50 bupivacaine-loaded microsphere); C (50% enantiomeric excess bupivacaine-loaded microsphere); and D (50% enantiomeric excess bupivacaine). Inhalation anesthesia was performed before the sciatic nerve block (2% halothane and 100% O2). Sensorial blockade was measured by the time required for each rat to withdraw its paw from a hot plate at 56ºC (positive > 4 sec). Motor blockade was measured by the time between drug injection until recovery of a motor score of 2 on the established criterion. RESULTS: The sensory response was significantly more frequent in groups B, C, and D than in group A (p < 0.001). There were no statistically significant differences in the response to the sensory test in groups B, C, and D (p > 0.05). The response to the motor test was also significantly more frequent in groups B, C, and D than in group A (p = 0.02). A tendency to greater positivity in the motor test was more frequently found in groups B and D than in group C (p = 0.10). CONCLUSIONS: Controlled-release of 50% enantiomeric excess bupivacaine-loaded microspheres showed similar results regarding analgesia and less motor blockade when compared to other anesthetic formulations.

Keywords

Pain, Microspheres, Bupivacaine, Rats

References

Borgeat A, Ekatodramis G, Schenker CA. Postoperative nausea and vomiting in regional anesthesia: A review. Anesthesiology. 2003;98:530-547.

Scurlock JE, Curtis BM. Tetraethylammonium derivatives: ultralongacting local anesthetics. Anesthesiology. 1981;54:265-269.

Lipfert P, Seitz RJ, Amdt JO. Ultralong-lasting nerve block: triethyldodecyl ammonium bromide is probably a neurotoxin rather than a local anesthetic. Anesthesiology. 1987;67:896-904.

Mulroy MF, Larkin KL, Batra MS. Femoral nerve block with 0.25% or 0.5% bupivacaine improves postoperative analgesia following outpatient arthroscopic anterior cruciate ligament repair. Reg Anesth Pain Med. 2001;26:24-29.

Ilfeld BM, Esener DE, Morey TE. Ambulatory perineural infusion: The patients' perspective. Reg Anesth Pain Med. 2003;28:418-423.

Neal JM, Hebl JR, Gerancher JC. Brachial plexus anesthesia: essentials of our current understanding. Reg Anesth Pain Med. 2002;27:402-428.

Legros F, Luo H, Bourgeois I. Influence of different liposomal formulation on the pharmacokinetics of encapsulated bupivacaine. Anesthesiology. 1990;73(^s3).

Blanco MD, Bernardo MV, Gomes C. Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactideco-glycolide) film: in vivo biocompatibility and drug release studies. Biomaterials. 1999;20:1919-1924.

Araújo DR, Pinto LM, Braga AFA. Formulações de anestésicos locais de liberação prolongada: aplicações terapêuticas. Rev Bras Anestesiol. 2003;53:663-671.

Araújo DR, Fraceto LF, Braga AFA. Sistemas de liberação controlada com bupivacaína racêmica (S50-R50) e mistura enantiomérica de bupivacaína (S75 R25): Efeitos da complexação com ciclodextrinas no bloqueio do nervo ciático em camundongos. Rev Bras Anestesiol. 2005;55:316-328.

Estebe JP, Corre PL, Malldant Y. Prolongation of spinal anesthesia with bupivacaine-loaded (DL- Lactide) microspheres. Anesth Analg. 1995;81:99-103.

Masters DB, Berde CB, Dutta SK. Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable plymer matrix. Anesthesiology. 1993;79:340-346.

Tanaka PP, Estèbe JP, Campos R. Preparação, caracterização e avaliação in vitro de microesferas de bupivacaína em excesso enantiomerico de 50% (S75-R25). Rev Bras Anestesiol. 2008;58(1):15-22.

Thalhammer JC, Vladimirova M, Bershadsky B. Neurological evaluation of the rat during sciatic nerve block with lidocaine. Anesthesiology. 1995;82:1013-25.

Le Corre P, Estèbe JP, Clément R. Spray-dryed bupivacaineloaded microspheres: in vitro evaluation and biopharmaceutics of bupivacaine following brachial plexus administration in sheep. Int J Pharm. 2002;238:191-203.

Ito Y, Hasuda H, Morimatsu M. A microfabrication method of a biodegradable polymer chip for a controlled release system. J Biomater Sci Polym Ed. 2005;16:949-955.

Wakiyama N, Juni K, Nakano M. Preparation and evaluation in vitro of polylactic acid microspheres containing local anesthetics. Chem. Pharm. Bull. 1981;29:3363-3368.

Le Corre P, Estèbe JP, Chevanne F. Spinal controlled delivery of bupivacaine from DL-lactic acid oligomer microspheres. J Pharm Sci. 1995;84:75-78.

Rose JS, Neal MN, Kopacz DJ. Extended-Duration Analgesia: Update on Microspheres and Lipossomes. Reg Anesth Pain Med. 2005;30:275-285.

Stephan FK, Zucker I. Rat drinking rhythms: central visual pathways and endocrine factors mediating responsiveness to environmental illumination. Physiol Behav. 1972;8(2):315-326.

Hu D, Hu R, Berde CB. Neurologic evaluation of infant and adult rats before and after sciatic nerve blockade. Anesthesiology. 1997;86:957-965.

Grant GJ, Vermeulen K, Zakowski MI. A at sciatic nerve model for independent assessment of sensory and motor block induced by local anesthetics. Anesth Anal. 1992;75:889-894.

Feldman HS, Covino BG. Comparative motorblocking effets of bupivacaine and ropivacaine, a new amino amide local anesthesic, in the rat and dog. Anesth Analg. 1988;67:1047-1052.

Curley J, Castillo J, Hotz J. Prolonged regional nerve block: Injectable biodegradable bupivacaine - polyester microspheres. Anesthesiology. 1996;84:1401-1410.

Kopacz DJ, Lacouture PG, Wuk D. The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostal blockade (T9-T11) in healthy volunteers. Anesth Analg. 2003;96:576-582.

Pedersen JL, Lillesø J, Hammer NA. Bupivacaine in microcapsules prolongs analgesia after subcutaneous infiltration in humans: a dose finding study. Anesth Analg. 2004;99:912-918.

Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs. 2000;59:551-579.

Simonetti MPB, Valinetti EA, Ferreira FM. Avaliação da atividade anestésica local da S(-) bupivacaína: estudo experimental in vivo em nervo ciático de rato. Rev Bras Anestesiol. 1997;47:425-434.

Malinovsky JM, Bernard JM, Corre PL. Motor and blood pressure effects of epidural sustained release bupivacaine from polymer microspheres: a dose respond study in rabbits. Anesth Analg. 1995;81:519-524.

Estebe JP, Myers RR. Amitripyline neurotoxicity: Dose-related pathology after topical topical application to rat sciatic nerve. Anesthesiology. 2004;100:1519-25.

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