法国南特大学Antoine Roquilly团队比较了瑞芬太尼与神经肌肉阻滞剂在快速顺序插管中对有误吸危险患者插管成功且无重大并发症的影响。2023年1月3日，该研究发表在《美国医学会杂志》上。

当与催眠剂一起使用时，快速起效的阿片类药物在快速顺序插管期间是否不劣于快速起效的神经肌肉阻滞剂，目前尚不确定。

为了确定瑞芬太尼在快速顺序插管中是否不劣于快速起效的神经肌肉阻滞药，2019年10月至2021年4月，研究组对在法国15家医院手术室进行气管插管的1150名有误吸风险（禁食<6小时、肠梗阻、近期外伤或严重胃食管反流）的成年人进行了一项多中心、随机、开放标签、非劣效性试验。随访于2021年5月15日完成。

将患者随机分组，分别接受神经肌肉阻断剂（1 mg/kg琥珀胆碱或罗库溴铵；n = 575）或瑞芬太尼（3至4 μg/kg；n = 575）。对所有随机患者（作为随机人群）和接受指定治疗的所有合格患者（按照方案人群）的主要结局进行评估。

主要结局是气管插管第一次尝试成功，没有出现重大并发症，如肺部吸入消化物、氧饱和度降低、严重血流动力学不稳定、持续性心律失常、心脏骤停和严重过敏反应。预先指定的非劣效性边缘为7.0%。

1150名随机患者（平均年龄为50.7岁；共573名女性，占50%）中，1130名（98.3%）完成了试验。在随机人群中，瑞芬太尼组575名患者中有374名（66.1%）首次尝试气管插管，且未出现严重并发症；神经肌肉阻滞组575名患者中有408名（71.6%），根据随机分层和中心调整的组间差异为-6.1%，表现出劣效性。

在符合方案的人群中，瑞芬太尼组565名患者中有374名（66.2%）成功插管且无重大并发症，神经肌肉阻滞组565名患者中有403名（71.3%），校正后的差异为-5.7%。瑞芬太尼组575名患者中有19名（3.3%）记录到血流动力学不稳定的不良事件，神经肌肉阻滞组575名患者中有3名（0.5%），校正后的差异为2.8%。

研究结果表明，在手术室快速顺序插管过程中有误吸风险的成年人中，瑞芬太尼与神经肌肉阻滞药相比，在首次尝试成功插管且无重大并发症方面不符合非劣效性标准。尽管瑞芬太尼在统计学上不如神经肌肉阻滞药，但效果评估的宽置信区间仍与非劣效性一致，限制了关于差异的临床相关性的结论。

附：英文原文

Title: Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial

Author: Nicolas Grillot, Gilles Lebuffe, Olivier Huet, Sigismond Lasocki, Xavier Pichon, Mathieu Oudot, Nathalie Bruneau, Jean-Stéphane David, Pierre Bouzat, Alexandra Jobert, Martine Tching-Sin, Fanny Feuillet, Raphael Cinotti, Karim Asehnoune, Antoine Roquilly, Atlanrea Study GroupSociété Franaise d’Anesthésie Réanimation (SFAR) Research Network, Pascal Incagnoli, Anne Li, Xavier PICHON, Amazigh AGUERSIF, Vincent MINVILLE, Martin DUPUIS, Matthias Garot, Florence Lallemant, Christine Ducam, Aurélien Rohn, Alexis Duchalais, Clément Starck, Maxime Lecourtois Du Manoir, Paul Rooze, Amelie Trichot, Romain Deransy, Benoit Plaud, Denis Frasca, Laura Leo

Issue&Volume: 2023/01/03

Abstract:

Importance  It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent.

Objective  To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation.

Design, Setting, and Participants  Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021.

Interventions  Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n=575) or remifentanil (3 to 4 μg/kg; n=575) immediately after injection of a hypnotic.

Main Outcomes and Measures  The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%.

Results  Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, –6.1%; 95% CI, –11.6% to –0.5%; P=.37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, –5.7%; 2-sided 95% CI, –11.3% to –0.1%; P=.32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%).

Conclusions and Relevance  Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference.

DOI: 10.1001/jama.2022.23550

Source: https://jamanetwork.com/journals/jama/article-abstract/2800025