Abstract：
BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients.
METHODS: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results.
RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance.
CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.
METHODS: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results.
RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance.
CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.
摘要：
背景：神经肌肉阻滞剂（NMBAs）的药代动力学和药效学与年龄相关的差异以及许多外科手术的持续时间短，使儿科患者面临术后残留curarization（PORC）的风险。迄今为止,儿童神经肌肉阻滞剂作用的持续时间尚未在定量审查中进行分析.当前的荟萃分析旨在比较各种类型和剂量的神经肌肉阻断剂给药后的自发恢复，并量化与儿科患者恢复时间相关的预后变量的影响。
方法：我们搜索了将时间与25％T1（t25）进行比较的随机对照试验（RCT）和对照临床试验（CCT），从25%到75%T1（RI25-75），在对健康儿科参与者进行单一推注的常见神经肌肉阻断剂治疗之间，以及≥90%的四组（tTOF90）神经肌肉恢复。我们比较了（1）神经肌肉阻滞剂治疗和（2）接受给定神经肌肉阻滞剂干预和麻醉技术的年龄组之间的自发t25，RI25-75和tTOF90。使用贝叶斯随机效应网络和成对meta分析以及meta回归来评估结果。
结果：我们使用了71项随机对照试验/包括4319名参与者的对照临床试验的数据。网络荟萃分析允许在常见的神经肌肉阻滞剂干预后，自发性t25，RI25-75和tTOF90的并置和排名。对于所有神经肌肉阻断剂，发现剂量与作用持续时间之间存在对数线性关系。随着神经肌肉阻断剂治疗的研究，儿童（>2-11岁）的平均tTOF90（平均[CrI95]）比新生儿（<28d）和婴儿（28d-12M）短41.96[14.35,69.50]和17.06[5.99,28.30]分钟，分别。我们发现年龄与神经肌肉阻滞剂作用持续时间之间存在负对数线性相关。使用氨基类固醇神经肌肉阻滞剂后，儿童和其他年龄组之间的tTOF90（平均[CrI95]）差异增加了21.66[8.82,34.53]min，而添加七氟醚/异氟醚用于维持麻醉则增加了24.73[7.92,41.43]min。
结论：神经肌肉恢复的时间是高度可变的。这些可以随着年龄的增长而显著降低,并且当施用挥发性麻醉剂时延长。这种可变性，加上许多儿科外科手术的持续时间短，即使在单剂量神经肌肉阻滞剂后，也必须进行定量神经肌肉监测。
方法：我们搜索了将时间与25％T1（t25）进行比较的随机对照试验（RCT）和对照临床试验（CCT），从25%到75%T1（RI25-75），在对健康儿科参与者进行单一推注的常见神经肌肉阻断剂治疗之间，以及≥90%的四组（tTOF90）神经肌肉恢复。我们比较了（1）神经肌肉阻滞剂治疗和（2）接受给定神经肌肉阻滞剂干预和麻醉技术的年龄组之间的自发t25，RI25-75和tTOF90。使用贝叶斯随机效应网络和成对meta分析以及meta回归来评估结果。
结果：我们使用了71项随机对照试验/包括4319名参与者的对照临床试验的数据。网络荟萃分析允许在常见的神经肌肉阻滞剂干预后，自发性t25，RI25-75和tTOF90的并置和排名。对于所有神经肌肉阻断剂，发现剂量与作用持续时间之间存在对数线性关系。随着神经肌肉阻断剂治疗的研究，儿童（>2-11岁）的平均tTOF90（平均[CrI95]）比新生儿（<28d）和婴儿（28d-12M）短41.96[14.35,69.50]和17.06[5.99,28.30]分钟，分别。我们发现年龄与神经肌肉阻滞剂作用持续时间之间存在负对数线性相关。使用氨基类固醇神经肌肉阻滞剂后，儿童和其他年龄组之间的tTOF90（平均[CrI95]）差异增加了21.66[8.82,34.53]min，而添加七氟醚/异氟醚用于维持麻醉则增加了24.73[7.92,41.43]min。
结论：神经肌肉恢复的时间是高度可变的。这些可以随着年龄的增长而显著降低,并且当施用挥发性麻醉剂时延长。这种可变性，加上许多儿科外科手术的持续时间短，即使在单剂量神经肌肉阻滞剂后，也必须进行定量神经肌肉监测。
