瑞马唑仑用于肥胖或参考范围BMI的阻塞性睡眠呼吸暂停儿童术前镇静的ED95：一项有偏硬币剂量探索研究。
Remimazolam ED95 for Preoperative Sedation in Children with Obstructive Sleep Apnea, with Obesity or a Reference-Range BMI: A Biased-Coin Dose-Finding Study.
文献信息
| PMID | 42857246 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Fan Xiao |
| 作者单位 | Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, People's Republic of China. |
| 期刊 | Drug design, development and therapy |
| SCI 分区 | Q1 |
| IF | 6.2 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 肥胖可能改变瑞马唑仑的总体重给药剂量，而阻塞性睡眠呼吸暂停会缩小呼吸安全边际。我们估计了肥胖或参考范围体重指数（BMI）儿童中方案定义的术前镇静的ED95。
方法： 在这项前瞻性、单中心序贯剂量探索研究中，80名3-17岁临床诊断为OSA并接受腺样体切除术和/或扁桃体切除术的儿童进入研究定义的肥胖组（年龄别BMI>第95百分位数）或参考BMI组（第25-84百分位数）（每组40名）。独立的有偏硬币序列使用总体重剂量，起始剂量为0.20 mg/kg，步长为0.05 mg/kg。反应定义为1分钟静脉推注完成后3分钟时Ramsay镇静评分（RSS）≥4。等渗回归和2000次自助重抽样得出ED95估计值和偏差校正百分位95%置信区间（CIs）。
结果： 肥胖组35/40（87.5%）的参与者和参考BMI组34/40（85.0%）的参与者出现反应。ED95估计值分别为0.38 mg/kg（95% CI，0.32-0.39）和0.44 mg/kg（95% CI，0.39-0.44）。差异为-0.05 mg/kg（95% CI，-0.13至0.05）。在15分钟观察期间，每组各有一名儿童出现低氧血症（SpO2 93%），经托下颌手法后缓解。一名参考BMI组参与者出现心动过缓（50次/分），对阿托品有反应。没有儿童平均动脉压下降≥30%。
结论： 对于1分钟瑞马唑仑推注后3分钟RSS≥4的方案特异性ED95值，肥胖儿童为0.38 mg/kg，参考范围BMI儿童为0.44 mg/kg。
英文摘要
BACKGROUND: Obesity may alter total-body-weight dosing of remimazolam, whereas obstructive sleep apnea narrows the respiratory safety margin. We estimated the ED95 for protocol-defined preoperative sedation in children with obesity or a reference-range body mass index (BMI).
METHODS: In this prospective, single-center sequential dose-finding study, 80 children aged 3-17 years with a clinical OSA diagnosis undergoing adenoidectomy and/or tonsillectomy entered study-defined obesity (BMI-for-age >95th percentile) or reference-BMI (25th-84th percentile) groups (40 each). Independent biased-coin sequences used total-body-weight doses, starting at 0.20 mg/kg with 0.05 mg/kg steps. The response was a Ramsay Sedation Scale (RSS) score ≥4 at 3 minutes after completion of a 1-minute intravenous bolus. Isotonic regression and 2000 bootstrap resamples yielded ED95 estimates and bias-corrected percentile 95% confidence intervals (CIs).
RESULTS: Responses occurred in 35/40 (87.5%) participants in the obesity group and 34/40 (85.0%) in the reference-BMI group. ED95 estimates were 0.38 mg/kg (95% CI, 0.32-0.39) and 0.44 mg/kg (95% CI, 0.39-0.44), respectively. The difference was -0.05 mg/kg (95% CI, -0.13 to 0.05). During 15-minute observation, one child per group developed hypoxemia (SpO2 93%) that resolved after a jaw-thrust maneuver. One reference-BMI participant developed bradycardia (50 beats/min), which responded to atropine. No child had a ≥30% decrease in mean arterial pressure.
CONCLUSION: The protocol-specific ED95 values of a 1-min remimazolam bolus for RSS ≥4 at 3 min were 0.38 mg/kg in children with obesity and 0.44 mg/kg in children with a reference-range BMI.