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      Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats Translated title: Efeitos do rocurônio, sugamadex e complexo rocurônio-sugamadex sobre a coagulação em ratos

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          Abstract

          Background and objectives

          Sugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats.

          Methods

          This is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group – 0.5 mL of intravenous saline; the Sugammadex Group – intravenous sugammadex (100 mg kg −1); and the Rocuronium-Sugammadex Group – intravenous solution with rocuronium (3.75 mg kg −1) and sugammadex (100 mg kg −1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups.

          Results

          Platelet counts, prothrombin times, and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group ( p = 0.035).

          Conclusions

          The rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.

          Resumo

          Introdução e objetivos

          O sugamadex é uma substância farmacológica alternativa capaz de reverter o bloqueio neuromuscular sem as limitações apresentadas pelos anticolinesterásicos. Entretanto, há relatos de transtornos de coagulação relacionados ao tratamento com sugamadex sem que mecanismos exatos de seus efeitos sobre a coagulação sejam totalmente compreendidos. O objetivo da presente pesquisa foi avaliar os efeitos de rocurônio, sugamadex e do complexo rocurônio-sugamadex sobre a coagulação em um modelo experimental com ratos.

          Métodos

          Este é um estudo randomizado experimental animal. Ratos Wistar foram aleatoriamente designados aos seguintes grupos: grupo controle; Grupo Ssal – 0,5 mL de solução salina intravenosa; Grupo sugamadex – sugamadex intravenoso (100 mg kg −1); e Grupo rocurônio-sugamadex – solução intravenosa com rocurônio (3,75 mg kg −1) e sugamadex (100 mg kg −1). A anestesia foi realizada utilizando-se isoflurano com ventilação controlada. Os fatores de coagulação foram medidos 10 minutos após o final do preparo pré-operatório e 30 minutos após a administração de drogas de acordo com os grupos escolhidos.

          Resultados

          Contagem de plaquetas, tempo de protrombina e tempo de tromboplastina parcial ativada foram semelhantes entre os grupos e entre os momentos dentro de cada grupo. Houve redução nos níveis de fibrinogênio plasmático entre os tempos 1 e 2 no grupo rocurônio-sugamadex ( p = 0,035).

          Conclusões

          O complexo rocurônio-sugamadex promoveu reduções na contagem de fibrinogênio plasmático, apesar de os níveis continuarem dentro dos limites normais.

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          Most cited references25

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          Dose translation from animal to human studies revisited.

          As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
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            Animal Experiments in Biomedical Research: A Historical Perspective

            Simple Summary This article reviews the use of non-human animals in biomedical research from a historical viewpoint, providing an insight into the most relevant social and moral issues on this topic across time, as well as to how the current paradigm for ethically and publically acceptable use of animals in biomedicine has been achieved. Abstract The use of non-human animals in biomedical research has given important contributions to the medical progress achieved in our day, but it has also been a cause of heated public, scientific and philosophical discussion for hundreds of years. This review, with a mainly European outlook, addresses the history of animal use in biomedical research, some of its main protagonists and antagonists, and its effect on society from Antiquity to the present day, while providing a historical context with which to understand how we have arrived at the current paradigm regarding the ethical treatment of animals in research.
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              Sugammadex: a review of its use in anaesthetic practice.

              Sugammadex (Bridion), a modified gamma-cyclodextrin, is the first selective relaxant binding agent indicated to reverse the neuromuscular blockade induced during general anaesthesia to facilitate surgical procedures. The mechanism of action of sugammadex differs from that of other commonly used reversal agents, such as neostigmine and edrophonium. In the EU, sugammadex is recommended for use in the reversal of rocuronium- or vecuronium-induced moderate or deep muscle relaxation in adult (including elderly) patients and reversal of rocuronium-induced moderate muscle relaxation in paediatric patients (aged 2-17 years). Sugammadex is also approved in Australia, Iceland, New Zealand and Norway. In clinical trials in adult surgical patients with relatively good health, sugammadex at recommended doses provided rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade with a low incidence of residual or recurrent neuromuscular blockade and was generally well tolerated. In paediatric patients, sugammadex effectively reversed rocuronium-induced neuromuscular blockade and was generally well tolerated. Several factors associated with the use of sugammadex have yet to be determined, such as the efficacy and safety in patients with poorer health or in those with neuromuscular disorders, the incidence of infrequent adverse events in larger patient populations and the cost effectiveness of the drug relative to existing reversal agents. Nevertheless, sugammadex is a useful addition to the reversal agents commonly employed in anaesthetic practice.
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                Author and article information

                Contributors
                Journal
                Braz J Anesthesiol
                Braz J Anesthesiol
                Brazilian Journal of Anesthesiology
                Elsevier
                0104-0014
                2352-2291
                16 October 2020
                Nov-Dec 2020
                16 October 2020
                : 70
                : 6
                : 635-641
                Affiliations
                [a ]Universidade Federal Fluminense, Niterói, RJ, Brazil
                [b ]Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
                [c ]Martini Hospital Groningen, Groningen, Netherlands
                [d ]Universidade Estadual Paulista (UNESP), São Paulo, SP, Brazil
                Author notes
                [* ]Corresponding author. estbraga@ 123456hotmail.com
                Article
                S0104-0014(20)30165-2
                10.1016/j.bjane.2020.10.004
                9373703
                33218691
                88735011-1fde-4c02-a1e0-a28fe1fea75d
                © 2020 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 September 2019
                : 23 August 2020
                Categories
                Experimental Trials

                sugammadex,rocuronium,blood coagulation,sugamadex,rocurônio,coagulação sanguínea

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