Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1016/j.bjane.2015.02.010
Brazilian Journal of Anesthesiology
Scientific Article

The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose

Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica

Mehmet Baykal; Necati Gökmen; Alper Doğ; an; Serhat Erbayraktar; Osman Yı; lmaz; Elvan Ocmen; Hale Aksu Erdost; Atalay Arkan

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Abstract

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Keywords

Rocuronium, Seizure, Central nervous system, Rat

Resumo

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

Palavras-chave

Rocurônio, Convulsão, Sistema nervoso central, Rato

References

Peduto V, Gungui P, Di Martino M. Accidental subarachnoid injection of pancuronium. Anesth Analg. 1989;69:516.

Sparr H, Wierda J, Proost J. Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients. BJA. 1997;78:267-73.

Tobias J. Continuous infusion of rocuronium in a paediatric intensive care unit. Can J Anaesth. 1996;43:353-7.

Tassonyi E, Fathi M, Hughes GJ. Cerebrospinal fluid concentrations of atracurium, laudanosine and vecuronium following clinical subarachnoid hemorrhage. Acta Anaesthesiol Scand. 2002;46:1236-41.

Savarese JJ, Caldwell JE, Lien CA, Miller RD. Pharmacology of muscle relaxants and their antagonists, anesthesia. 2000:412-90.

Cardone C, Szenohradszky J, Yost S. Activation of brain acetylcholine receptors by neuromuscular blocking drugs: a possible mechanism of neurotoxicity. Anesthesiology. 1994;80:1155-9.

Fuchs-Buder T, Strowitzki M, Rentsch K. Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping. BJA. 2004;92:419-21.

Matteo RS, Pua EK, Khambatta HJ. Cerebrospinal fluid levels of d-tubocurarine in man. Anesthesiology. 1977;46:396.

Segredo V, Matthay MA, Sharma ML. Prolonged neuromuscular blockade after long-term administration of vecuronium in two critically ill patients. Anesthesiology. 1990;72:566-70.

Hennis PJ, Fahey MR, Canfell PC. Pharmacology of laudanosine in dogs. Anesthesiology. 1986;65:56-60.

Szenohradszky J, Trevor AJ, Bickler P. Central nervous system effects of intrathecal muscle relaxants in awake rats. Anesth Analg. 1993;76:1304-9.

Vassilikos D, Tsakiliotis S, Veroniki F. Inadvertent epidural administration of cisatracurium. EJA. 2004;21:663-72.

Kostopanagitou G, Mylona M, Massoura L. Accidental epidural injection of vecuronium. Anesth Analg. 2000;91:1550-1.

Cesur M, Alıcı H, Erdem A. Accidental caudal injection of rocuronium in an awake patient. Anesthesiology. 2005;103:444-5.

Stoelting RK, Miller RD. Neuromuscular blocking drugs, anesthesia. 2000:89-106.

Bartkowski RR, Witlkowski TA, Azad S. Rocuronium onset of action: a comparison with atracurium and vecuronium. Anesth Analg. 1993;77:574-8.

Khalil M, D'Honneur G, Duvalestin P. Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. Anesthesiology. 1994;6:241-5.

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