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

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 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.

[Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats]. / Efeitos do rocurônio, sugamadex e complexo rocurônio­sugamadex sobre a coagulação em ratos.

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.

Reversal of neuromuscular block with sugammadex in five heart transplant pediatric recipients / Reversão do bloqueio neuromuscular com sugamadex em cinco receptores pediátricos de transplante cardíaco

Abstract Heart transplantation is a frequent procedure in the treatment of end-stage cardiac dysfunction. Therefore, these patient populations will also be more frequent exposed to other more common surgical procedures after their transplantation. Anesthesiologist should be aware in their assessment of these patients, especially regarding some specific issues related to patients with a history of heart transplantation, like reversal of neuromuscular block. Several reports described that cholinesterase inhibitors drugs, like neostigmine, may produce a dose-dependent life-threatening bradycardia in heart transplant recipients while other publication described the safe use of neostigmine. Reversal of neuromuscular block with sugammadex is another possibility, but limited data exists in literature. We describe five cases in which successful reversal of neuromuscular block was performed with sugammadex in heart transplant pediatric recipients without sequale and discuss the reversal of neuromuscular block in this patient population.

Resumo O transplante cardíaco é um procedimento frequente no tratamento da disfunção cardíaca em estágio final. Portanto, essa população de pacientes também será exposta com mais frequência a outros procedimentos cirúrgicos mais comuns após o transplante. Em sua avaliação, o anestesiologista deve ter em mente algumas questões específicas relacionadas à história de transplante cardíaco desses pacientes, tais como a reversão do bloqueio neuromuscular. Vários estudos relataram que os inibidores da colinesterase, como a neostigmina, podem produzir uma bradicardia dose-dependente que ameaça a vida em receptores de transplante cardíaco, enquanto um estudo relatou o uso seguro de neostigmina. A reversão do bloqueio neuromuscular com sugamadex é outra possibilidade, mas os dados na literatura são escassos. Descrevemos cinco casos nos quais a reversão bem-sucedida do bloqueio neuromuscular foi realizada com sugamadex em receptores pediátricos de transplante cardíaco sem deixar sequelas e discutimos a reversão do bloqueio neuromuscular nessa população de pacientes.