PDF(Pubmed)
Abstract：
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.
To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation.
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.
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.
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%.
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%).
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.
ClinicalTrials.gov Identifier: NCT03960801.
To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation.
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.
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.
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%.
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%).
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.
ClinicalTrials.gov Identifier: NCT03960801.
摘要：
未经证实：当与催眠药联合使用时，在快速序列插管期间，快速起效的阿片类药物是否不劣于快速起效的神经肌肉阻滞剂尚不确定。
UNASSIGNED：确定瑞芬太尼在快速序列插管中是否不劣于快速发作的神经肌肉阻滞剂。
未经评估：多中心，随机化，开放标签，在1150名有误吸风险的成年人中进行非劣效性试验(禁食<6小时，肠闭塞,最近的创伤,或严重的胃食管反流），于2019年10月至2021年4月在法国15家医院的手术室接受了气管插管。后续行动于2021年5月15日完成。
UNASSIGNED：患者在注射催眠药后立即随机接受神经肌肉阻滞剂（1mg/kg琥珀酰胆碱或罗库溴铵；n=575）或瑞芬太尼（3至4μg/kg；n=575）。
UNASSIGNED：在所有随机患者（随机人群）和所有接受指定治疗的合格患者（按方案人群）中评估主要结果。主要结果是首次尝试成功气管插管，没有重大并发症。定义为消化内容物的肺吸入，氧饱和度,主要血流动力学不稳定，持续性心律失常,心脏骤停,和严重的过敏反应.预设的非劣效性边缘为7.0%。
未经评估：在1150名随机患者中（平均年龄，50.7[SD,17.4]年；573[50%]女性)，1130（98.3%）完成试验。在随机化的人群中，瑞芬太尼组575例患者中的374例(66.1%)和神经肌肉阻滞剂组575例患者中的408例(71.6%)首次尝试气管插管时没有发生重大并发症(组间差异根据随机分层和中心进行了调整,-6.1%；95%CI，-11.6%至-0.5%；非劣效性P=0.37），表现出自卑。在符合协议的人群中，瑞芬太尼组565例患者中的374例（66.2％）和神经肌肉阻滞剂组565例患者中的403例（71.3％）成功插管，无主要并发症（调整后的差异，-5.7%；双侧95%CI，-11.3%至-0.1%；非劣效性P=0.32）。在使用瑞芬太尼的575例患者中，有19例（3.3％）和使用神经肌肉阻滞剂的575例患者中，有3例（0.5％）记录了血流动力学不稳定的不良事件（调整后的差异，2.8%；95%CI，1.2%-4.4%）。
UASSIGNED：在手术室快速顺序插管期间有误吸风险的成年人中，瑞芬太尼,与神经肌肉阻滞剂相比，在没有重大并发症的情况下，首次尝试成功插管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剂，效应估计值周围的宽置信区间仍然与非劣效性相符,并且限制了关于差异的临床相关性的结论.
UNASSIGNED：ClinicalTrials.gov标识符：NCT03960801。
UNASSIGNED：确定瑞芬太尼在快速序列插管中是否不劣于快速发作的神经肌肉阻滞剂。
未经评估：多中心，随机化，开放标签，在1150名有误吸风险的成年人中进行非劣效性试验(禁食<6小时，肠闭塞,最近的创伤,或严重的胃食管反流），于2019年10月至2021年4月在法国15家医院的手术室接受了气管插管。后续行动于2021年5月15日完成。
UNASSIGNED：患者在注射催眠药后立即随机接受神经肌肉阻滞剂（1mg/kg琥珀酰胆碱或罗库溴铵；n=575）或瑞芬太尼（3至4μg/kg；n=575）。
UNASSIGNED：在所有随机患者（随机人群）和所有接受指定治疗的合格患者（按方案人群）中评估主要结果。主要结果是首次尝试成功气管插管，没有重大并发症。定义为消化内容物的肺吸入，氧饱和度,主要血流动力学不稳定，持续性心律失常,心脏骤停,和严重的过敏反应.预设的非劣效性边缘为7.0%。
未经评估：在1150名随机患者中（平均年龄，50.7[SD,17.4]年；573[50%]女性)，1130（98.3%）完成试验。在随机化的人群中，瑞芬太尼组575例患者中的374例(66.1%)和神经肌肉阻滞剂组575例患者中的408例(71.6%)首次尝试气管插管时没有发生重大并发症(组间差异根据随机分层和中心进行了调整,-6.1%；95%CI，-11.6%至-0.5%；非劣效性P=0.37），表现出自卑。在符合协议的人群中，瑞芬太尼组565例患者中的374例（66.2％）和神经肌肉阻滞剂组565例患者中的403例（71.3％）成功插管，无主要并发症（调整后的差异，-5.7%；双侧95%CI，-11.3%至-0.1%；非劣效性P=0.32）。在使用瑞芬太尼的575例患者中，有19例（3.3％）和使用神经肌肉阻滞剂的575例患者中，有3例（0.5％）记录了血流动力学不稳定的不良事件（调整后的差异，2.8%；95%CI，1.2%-4.4%）。
UASSIGNED：在手术室快速顺序插管期间有误吸风险的成年人中，瑞芬太尼,与神经肌肉阻滞剂相比，在没有重大并发症的情况下，首次尝试成功插管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剂，效应估计值周围的宽置信区间仍然与非劣效性相符,并且限制了关于差异的临床相关性的结论.
UNASSIGNED：ClinicalTrials.gov标识符：NCT03960801。
