Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model

Ying-Dong Lian; Zong-Xiang Chen; Kang-Ru Zhu; Shu-Yin Sun; Li-Ping Zhu

doi:10.1016/j.bjane.2015.08.006

Scientific Article

Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model

Efeito de doses equipotentes de bupivacaína e ropivacaína em modelo de roedor neonatal alimentado com dieta rica em gordura

Ying-Dong Lian; Zong-Xiang Chen; Kang-Ru Zhu; Shu-Yin Sun; Li-Ping Zhu

http://dx.doi.org/10.1016/j.bjane.2015.08.006 Braz J Anesthesiol, vol.67, n2, p.131-138, 2017

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Abstract

Abstract Objectives: The increase in the prevalence of obesity presents a significant health and economic problem. Obesity has been reported to be a major contributor to variety of chronic diseases. Childhood obesity has been rising over the past decades leading to various complications in health. Millions of infants and children undergo surgery every year on various health grounds. The present investigation was undertaken to evaluate the effect of spinal anesthesia of equipotent doses of ropivacaine and bupivacaine on over-weight neonatal rats. Methods: The Sprague-Dawley rat pups were overfed on high fat diet to induce obesity. Behavioral assessments for sensory and motor blockade was made by evaluating thermal and mechanical withdrawal latencies at various time intervals following intrathecal injections of bupivacaine (5.0 mg·kg-1) and ropivacaine (7.5 mg·kg-1) in P14 rats. Spinal tissue was analyzed for apoptosis by determination of activated caspase-3 using monoclonal anti-activated caspase-3 and Fluoro-Jade C staining. Long-term spinal function in P30 rat pups was evaluated. Results: Exposure to intrathecal anesthesia in P14 increased thermal and mechanical latencies and was observed to increase apoptosis as presented by increase in activated caspase-3 and Fluro-Jade C positive cells. Significant alterations in spinal function were observed in high fat diet-fed pups as against non-obese control pups that were on standard diet. Bupivacaine produced more pronounced apoptotic effects on P14 pups; ropivacaine however produced long lasting effects as evidenced in motor function tests at P30. Conclusion: Ropivacaine and bupivacaine induced spinal toxicity that was more pronounced in over-fed rat pups as against normal controls.

Keywords

Bupivacaine, Ropivacaine, Intrathecal anesthesia, Spinal toxicity, Obesity

Resumo

Resumo Objetivos: O aumento da prevalência da obesidade é um problema sério de saúde e econômico. A obesidade tem sido relatada como um dos principais contribuintes para uma variedade de doenças crônicas. A obesidade infantil tem aumentado nas últimas décadas e levado a complicações de saúde. Milhões de bebês e crianças são submetidos a cirurgia todos os anos por diversos motivos de saúde. O presente estudo foi feito para avaliar o efeito da raquianestesia com doses equipotentes de ropivacaína e bupivacaína em ratos recém-nascidos com sobrepeso. Métodos: As crias de ratos Sprague-Dawley foram alimentadas em excesso com dieta rica em gordura para induzir obesidade. Avaliações comportamentais para bloqueio sensorial e motor foram feitas por meio da avaliação das latências de retirada térmicas e mecânicas em vários intervalos de tempo após injeções por via intratecal de bupivacaína (5,0 mg·kg-1) e ropivacaína (7,5 mg·kg-1) em ratos P14. Tecido medular foi analisado para apoptose por determinação da caspase-3 ativada, com o uso de anticorpo monoclonal anti-caspase 3 ativada e ecoloração com Fluoro-Jade C. A função da coluna vertebral em longo prazo em filhotes de ratos P30 foi avaliada. Resultados: A exposição à anestesia intratecal em P14 aumentou as latências térmicas e mecânicas e observamos aumento da apoptose, como apresentado pelo aumento da caspase-3 ativada e células positivas para Fluro-Jade C. Alterações significativas da função da coluna vertebral foram observadas em filhotes alimentados com dieta rica em gordura versus filhotes controles não obesos em dieta padrão. Bupivacaína produziu efeitos apoptóticos mais pronunciados sobre os filhotes P14; ropivacaína, entretanto, produziu efeitos duradouros, como evidenciado nos testes de função motora em P30. Conclusão: Ropivacaína e bupivacaína induziram toxicidade medular mais pronunciada nos filhotes de ratos sobrealimentados do que nos controles normais.

Palavras-chave

Bupivacaína, Ropivacaína, Anestesia intratecal, Toxicidade medular, Obesidade

References

Reilly JJ. Obesity in childhood and adolescence: evidence based clinical and public health perspectives. Postgrad Med J. 2006;82:429-37.

de Onis M, Blossner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr. 2010;92:1257-64.

WHO Fact Sheet: childhood overweight and obesity. .

Guo SS, Wu W, Chumlea WC. Predicting overweight and obesity in adulthood from body mass index values in childhood and adolescence. Am J Clin Nutr. 2002;76:653-8.

Nader PR, O'Brien M, Houts R. Identifying risk for obesity in early childhood. Pediatrics. 2006;118:e594-601.

Bjorntorp P. Obesity. Lancet. 1997;350:423-6.

Abernethy DR, Greenblatt DJ. Drug disposition in obese humans. An update. Clin Pharmacokinet. 1986;11:199-213.

Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesthesiol. 2000;85:91-108.

Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39:215-31.

Kuczkowski KM, Benumof JL. Repeat cesarean section in a morbidly obese parturient: a new anesthetic option. Acta Anaesthesiol Scand. 2002;46:753-4.

Sice PJ, Chan D, MacIntyre PA. Epidural analgesia after spinal surgery via intervertebral foramen. Br J Anaesth. 2005;94:378-80.

Morgan MM. Clinical anaesthesiology. 2006:263-75.

Markham A, Faulds D. Ropivacaine: a review of its pharmacology and therapeutic use in regional anesthesia. Drugs. 1996;52:429-49.

Catterall WA, Mackie K. Local anesthetics. Goodman and Gilman's Manual of Pharmacology and Therapeutics. 2008:241-52.

Hu D, Hu R, Berde CB. Neurologic evaluation of infant and adult rats before and after sciatic nerve blockade. Anesthesiology. 1997;86:957-65.

Kohane D, Sankar W, Shubina M. Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine. Anesthesiology. 1998;89:1199-208.

Walker SM, Howard RF, Keay KA. Developmental age influences the effect of epidural dexmedetomidine on inflammatory hyperalgesia in rat pups. Anesthesiology. 2005;102:1226-34.

Sanders RD, Xu J, Shu Y. General anesthetics induce apoptotic neurodegeneration in the neonatal rat spinal cord. Anesth Analg. 2008;106:1708-11.

Wilder RT, Flick RP, Sprung J. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110:796-804.

Flick RP, Katusic SK, Colligan RC. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011;128:e1053-61.

Jevtovic-Todorovic V, Hartman RE, Izumi Y. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003;23:876-82.

Brambrink AM, Evers AS, Avidan MS. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010;112:834-41.

Gentry KR, Steele LM, Sedensky MM. Early developmental exposure to volatile anesthetics causes behavioral defects in Caenorhabditis elegans. Anesth Analg. 2013;116:185-9.

Sun X, Garlid KD. On the mechanism by which bupivacaine conducts protons across the membranes of mitochondria and liposomes. J Biol Chem. 1992;267:19147-54.

Lee H, Sowa G, Vo N. Effect of bupivacaine on intervertebral disc cell viability. Spine J. 2010;10:159-66.

Bosenberg A, Thomas J, Lopez T. The efficacy of caudal ropivacaine 1, 2 and 3 mg/ml for postoperative analgesia in children. Paediatr Anaesth. 2002;12:53-8.

Hansen TG. Ropivacaine: a pharmacological review. Expert Rev Neurother. 2004;4:781-91.

Pitkanen MT. Body mass and spread of spinal anesthesia with bupivacaine. Anesth Analg. 1987;66:127-31.

Schnider TW, Minto CF, Bruckert H. Population pharmacodynamic modeling and covariate detection for central neural blockade. Anesthesiology. 1996;85:502-12.

McCulloch WJ, Littlewood DG. Influence of obesity on spinal analgesia with isobaric 0.5% bupivacaine. Br J Anaesth. 1986;58:610-4.

Taivainen T, Tuominen M, Rosenberg PH. Influence of obesity on the spread of spinal analgesia after injection of plain 0.5% bupivacaine at the L3-4 or L4-5 interspace. Br J Anaesth. 1990;64:542-6.

Barclay DL, Renegar OJ, Nelson Jr. EW. The influence of inferior vena cava compression on the level of spinal anesthesia. Am J Obstet Gynecol. 1968;101:792-800.

Carvalho B, Collins J, Drover DR. ED(50) and ED(95) of intrathecal bupivacaine in morbidly obese patients undergoing cesarean delivery. Anesthesiology. 2011;114:529-35.

Kim WH, Lee JH, Ko JS. The effect of body mass index on spinal anaesthesia for total knee replacement arthroplasty: a dose-response study. Anaesth Intensive Care. 2012;40:410-6.

Leino KA, Kuusniemi KS, Palve HK. The effect of body mass index on the spread of spinal block in patients with rheumatoid arthritis. J Anesth. 2011;25:213-8.

Effect of equipotent doses of bupivacaine and ropivacaine in high-fat diet fed neonatal rodent model

Efeito de doses equipotentes de bupivacaína e ropivacaína em modelo de roedor neonatal alimentado com dieta rica em gordura

Ying-Dong Lian; Zong-Xiang Chen; Kang-Ru Zhu; Shu-Yin Sun; Li-Ping Zhu

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