Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2020.10.004
Brazilian Journal of Anesthesiology
Experimental Trials

Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats

Efeitos do rocurônio, sugamadex e complexo rocurônio-sugamadex sobre a coagulação em ratos

Estêvão Luiz Carvalho Braga, Ismar Cavalcanti, Nubia Verçosa, Alberto Schanaider, Louis Barrucand, Hans Donald de Boer, Luiz Vane

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Abstract

Background and objectives
Sugammadex are an alternative pharmacological drug that is 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). Anaesthesia 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.

Keywords

Sugammadex,  Rocuronium,  Blood coagulation

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 do 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.

Palavras-chave

Sugamadex,  Rocurônio,  Coagulação sanguínea

References

1 G.V. Kumar, A.P. Nair, H.S. Murthy, et al. Residual neuromuscular blockade affects postoperative pulmonary function Anesthesiology., 117 (2012), pp. 1234-1244

2 C. Baillard Incidence and complications of post operative residual paralysis Ann Fr Anesth Reanim., 28 (Suppl. 2) (2009), pp. S41-S45

3 L.H. Booij, J. Van Egmond, J.J. Driessen, et al. In vivo animal studies with sugammadex Anaesthesia., 64 (Suppl. 1) (2009), pp. S38-S44

4 H.D. De Boer, J. Van Egmond, J.J. Driessen, et al. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex Rev Esp Anestesiol Reanim., 57 (2010), pp. 181-184

5 L.P. Yang, S.J. Keam Sugammadex: a review of its use in anaesthetic practice Drugs., 69 (2009), pp. 919-942

6 P.A. Peeters, M.W. Van den Heuvel, E. Van Heumen, et al. Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg.kg-1) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study Clin Drug Invest., 30 (2010), pp. 867-874

7 J. Raft, J.F.B. Belinga, G. Jurkolow, et al. Clinical evaluation of post-surgical bleeding after a sugammadex injection Ann Fr Anesth Reanim., 30 (2011), pp. 714-717

8 N. Tas, H. Korkmaz, O. Yagan, et al. Effect of sugammadex on postoperative bleeding and coagulation parameters after septoplasty: a randomized prospective study Med Sci Monit., 21 (2015), pp. 2382-2386

9 Y.J. Moon, S.H. Kim, J.W. Kim, et al. Comparison of postoperative coagulation profiles and outcome for sugammadex versus pyridostigmine in 992 living donors after living-donor hepatectomy Medicine (Baltimore)., 97 (2018), p. e0129

10 P.J. De Kam, P. Grobara, M. Prohn, et al. Effects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects Int J Clin Pharmacol Ther., 52 (2014), pp. 227-236

11 S. Reagan-Shaw, M. Nihal, N. Ahmad Dose translation from animal to human studies revisited FASEB J., 22 (2008), pp. 659-661

12 T. Murata, T. Kubodera, M. Ohbayashi, et al. Recurarization after sugammadex following a prolonged rocuronium infusion for induced hypothermia Can J Anaesth., 60 (2013), pp. 508-509

13 M. Melo, G. Dória, M. Serafini Valores de referência hematológicos e bioquímicos de ratos (Rattus novergicus linhagem Wistar) provenientes do biotério central da Universidade Federal do Sergipe Scientia Plena., 8 (2012), pp. 1-6

14 D. Fries, W.Z. Martini Role of fibrinogen in trauma-induced coagulopathy Br J Anaesth., 105 (2010), pp. 116-121

15 M.M.L. Carlos, P.D.F.S. de Freitas Estudo da cascata de coagulação sangüínea e seus valores de referência Acta Vet Bras., 1 (2007), pp. 49-55

16 N. Rahe-Meyer, H. Fennema, S. Schulman, et al. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients Anesthesiology., 121 (2014), pp. 969-977

17 N. Taş, Ö. Yağan, T. Noyan, et al. Effect of low and high dose sugammadex on the coagulation and fibrinolytic system in rats Advances in Anesthesiology., 2015 (2015), p. 708915

18 D. Dirkmann, M.W. Britten, H. Pauling, et al. Anticoagulant effect of sugammadex: just an in vitro artifact Anesthesiology., 124 (2016), pp. 1277-1285

19 M. Carron Bleeding risk in surgical patients receiving sugammadex: definitive conclusions are not yet possible Anesthesiology., 123 (2015), p. 1212

20 I.O. Lee, Y.S. Kim, H.W. Chang, et al. In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients BMC Anesthesiology., 18 (2018), p. 56

21 N.H. Franco Animal experiments in biomedical research: A historical perspective Animals., 3 (2013), pp. 238-273

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