舒更葡糖钠用于ASA分级Ⅲ或Ⅳ级高风险手术患者安全性的评价:随机双盲临床研究

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants

目的评价舒更葡糖钠用于ASA分级Ⅲ或Ⅳ级高风险手术患者术后拮抗神经肌肉阻滞的安全性。尤其着重评估了心脏不良事件以及其他预先指定的临床关注不良事件的影响。方法符合ASA分级Ⅲ或Ⅳ级标准的患者,根据ASA分级和神经肌肉阻滞剂(罗库溴铵或维库溴铵)进行随机分组,新斯的明/格隆溴铵组:中度神经肌肉阻滞;舒更葡糖钠2 mg/kg组,中度神经肌肉阻滞;舒更葡糖钠4 mg/kg组,深度神经肌肉阻滞;舒更葡糖钠16 mg/kg组,深度神经肌肉阻滞(仅罗库溴铵)。主要研究终点包括治疗期间窦性心动过缓、窦性心动过速和其他心律失常的发生情况。结果344例患者进入随机化分配,331例患者接受了治疗[61%为男性,BMI(28.5±5.3)kg/m^(2),年龄(69±11)岁]。舒更葡糖钠2 mg/kg组治疗期间窦性心动过缓发生率显著降低,舒更葡糖钠2 mg/kg组和4 mg/kg组治疗期间窦性心动过速发生率显著降低(P<0.05)。4组间治疗期间其他心律失常发生率比较差异无统计学意义(P>0.05)。结论ASA分级Ⅲ或Ⅳ级高风险手术患者使用舒更葡糖钠拮抗罗库溴铵或维库溴铵诱导的中度和深度神经肌肉阻滞的安全性良好。

Objective The aim of this randomized,double-blind trial was to evaluate the safety and tolerability profile,including cardiac safety,of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists(ASA)Physical Class 3 or 4 criteria.Specifically,this study assessed the impact of sugammadex on cardiac adverse events(AEs)and other prespecified AEs of clinical interest.Methods Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA(rocuronium or vecuronium)then randomized to one of the following:1)Moderate neuromuscular block,sugammadex 2 mg/kg;2)Moderate neuromuscular block,neostigmine and glycopyrrolate(neostigmine/glycopyrrolate);3)Deep neuromuscular block,sugammadex 4 mg/kg;4)Deep neuromuscular block,sugammadex 16 mg/kg(rocuronium only).Primary endpoints included incidences of treatment-emergent(TE)sinus bradycardia,TE sinus tachycardia and other TE cardiac arrhythmias.Results Of 344 participants randomized,331 received treatment(61%male,BMI 28.5±5.3 kg/m^(2),age 69±11 years).Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate.The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate.No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate.There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study.Conclusions Compared with neostigmine/glycopyrrolate,incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg.These results support the safety of sugammadex for reversing rocuronium-or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants.